Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C14H19BCl2N2O4 |
| Molecular Weight | 361.029 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)C[C@H](NC(=O)CNC(=O)C1=C(Cl)C=CC(Cl)=C1)B(O)O
InChI
InChIKey=MXAYKZJJDUDWDS-LBPRGKRZSA-N
InChI=1S/C14H19BCl2N2O4/c1-8(2)5-12(15(22)23)19-13(20)7-18-14(21)10-6-9(16)3-4-11(10)17/h3-4,6,8,12,22-23H,5,7H2,1-2H3,(H,18,21)(H,19,20)/t12-/m0/s1
DescriptionSources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208462s001lbl.pdf | http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003844/WC500217620.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208462lbl.pdfCurator's Comment: description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT02630030 | https://www.ncbi.nlm.nih.gov/pubmed/24486586 | https://www.ncbi.nlm.nih.gov/pubmed/25016815 | https://www.ncbi.nlm.nih.gov/pubmed/25605842
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208462s001lbl.pdf | http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003844/WC500217620.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208462lbl.pdf
Curator's Comment: description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT02630030 | https://www.ncbi.nlm.nih.gov/pubmed/24486586 | https://www.ncbi.nlm.nih.gov/pubmed/25016815 | https://www.ncbi.nlm.nih.gov/pubmed/25605842
Ixazomib (trade name Ninlaro) is a drug for the treatment of multiple myeloma in adults after at least one prior therapy, in combination with lenalidomide and dexamethasone. It is taken by mouth in form of capsules. Common side effects include diarrhea, constipation and low platelet count. Like the older bortezomib (which can only be given by injection), it acts as a proteasome inhibitor, has orphan drug status in the US and Europe. At therapeutic concentrations, ixazomib selectively and reversibly inhibits the protein proteasome subunit beta type-5 (PSMB5) with a dissociation half-life of 18 minutes. This mechanism is the same as of bortezomib, which has a much longer dissociation half-life of 110 minutes; the related drug carfilzomib, by contrast, blocks PSMB5 irreversibly. Proteasome subunits beta type-1 and type-2 are only inhibited at high concentrations reached in cell culture models. PSMB5 is part of the 20S proteasome complex and has enzymatic activity similar to chymotrypsin. It induces apoptosis, a type of programmed cell death, in various cancer cell lines. A synergistic effect of ixazomib and lenalidomide has been found in a large number of myeloma cell lines. The medication is taken orally as a prodrug, ixazomib citrate, which is a boronic ester; this ester rapidly hydrolyzes under physiological conditions to its biologically active form, ixazomib, a boronic acid. Absolute bioavailability is 58%, and highest blood plasma concentrations of ixazomib are reached after one hour. Plasma protein binding is 99%.
CNS Activity
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003844/WC500217620.pdfhttps://clinicaltrials.gov/ct2/show/NCT02630030
Curator's Comment: Following oral administration, a tissue distribution study in rats revealed that the brain and spinal cord were amongst the tissues with the lowest levels, suggesting that the penetration of ixazomib through the blood-brain barrier appears to be limited. However, the relevance to humans is unknown.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: P28074|||Q86T01 Gene ID: 5693.0 Gene Symbol: PSMB5 Target Organism: Homo sapiens (Human) |
0.93 nM [Ki] | ||
Target ID: P28074|||Q86T01 Gene ID: 5693.0 Gene Symbol: PSMB5 Target Organism: Homo sapiens (Human) |
3.4 nM [IC50] | ||
Target ID: P49721 Gene ID: 5690.0 Gene Symbol: PSMB2 Target Organism: Homo sapiens (Human) |
3500.0 nM [IC50] | ||
Target ID: P20618 Gene ID: 5689.0 Gene Symbol: PSMB1 Target Organism: Homo sapiens (Human) |
31.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | NINLARO Approved UseNINLARO is a proteasome inhibitor indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Launch Date1.44797755E12 |
|||
| Primary | NINLARO Approved UseINDICATIONS AND USAGE. NINLARO is a proteasome inhibitor indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Launch Date1.44797755E12 |
|||
| Primary | NINLARO Approved UseINDICATIONS AND USAGE. NINLARO is a proteasome inhibitor indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Launch Date1.44797755E12 |
|||
| Primary | NINLARO Approved UseINDICATIONS AND USAGE. NINLARO is a proteasome inhibitor indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Launch Date1.44797755E12 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
77 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26872892 |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
22.8 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26872892 |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
77 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26872892/ |
4 mg 3 times / 2 weeks multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
25.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27196567/ |
3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
22.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26872892/ |
4 mg 3 times / 2 weeks multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1470 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26872892 |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
999 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26872892 |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
1470 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26872892/ |
4 mg 3 times / 2 weeks multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
575 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27196567/ |
3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
999 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26872892/ |
4 mg 3 times / 2 weeks multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
1161.92 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1.33 mg/m^2 1 times / 3 days multiple, intravenous dose: 1.33 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
1542.63999999999 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1.76 mg/m^2 1 times / 3 days multiple, intravenous dose: 1.76 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
191.87 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1 mg/m^2 single, intravenous dose: 1 mg/m^2 route of administration: intravenous experiment type: single co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
301 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
0.5 mg/m^2 1 times / 3 days multiple, intravenous dose: 0.5 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
3800 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
2.34 mg/m^2 1 times / 3 days multiple, intravenous dose: 2.34 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
391.46 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1.33 mg/m^2 single, intravenous dose: 1.33 mg/m^2 route of administration: intravenous experiment type: single co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
522.74 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1.76 mg/m^2 single, intravenous dose: 1.76 mg/m^2 route of administration: intravenous experiment type: single co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
579.91 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1 mg/m^2 1 times / 3 days multiple, intravenous dose: 1 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
60.9 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
0.25 mg/m^2 1 times / 3 days multiple, intravenous dose: 0.25 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
620 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
2.34 mg/m^2 single, intravenous dose: 2.34 mg/m^2 route of administration: intravenous experiment type: single co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
91.6 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
0.5 mg/m^2 single, intravenous dose: 0.5 mg/m^2 route of administration: intravenous experiment type: single co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
144.69 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1.33 mg/m^2 1 times / 3 days multiple, intravenous dose: 1.33 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
104.84 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1.76 mg/m^2 1 times / 3 days multiple, intravenous dose: 1.76 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
90.8 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
2.34 mg/m^2 1 times / 3 days multiple, intravenous dose: 2.34 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
171.9 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1 mg/m^2 1 times / 3 days multiple, intravenous dose: 1 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
9.5 day EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28290121/ |
multiple, oral |
IXAZOMIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27196567/ |
3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1% |
IXAZOMIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
1.76 mg/m2 3 times / month multiple, intravenous Dose: 1.76 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 1.76 mg/m2, 3 times / month Sources: |
unhealthy, 45 years (range: 23–73 years) n = 7 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 45 years (range: 23–73 years) Sex: M+F Population Size: 7 Sources: |
DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 4, 1 patient) Sources: |
3.11 mg/m2 3 times / month multiple, intravenous Highest studied dose Dose: 3.11 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 3.11 mg/m2, 3 times / month Sources: |
unhealthy, 56 years (range: 27–72 years) n = 5 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 56 years (range: 27–72 years) Sex: M+F Population Size: 5 Sources: |
DLT: Acute renal failure, Diarrhea... Dose limiting toxicities: Acute renal failure (grade 3, 1 patient) Sources: Diarrhea (grade 2-3, 2 patients) Vomiting (grade 2-3, 2 patients) Fatigue (grade 2, 1 patient) Nausea (grade 2, 1 patient) |
5.5 mg 3 times / month multiple, oral Highest studied dose Dose: 5.5 mg, 3 times / month Route: oral Route: multiple Dose: 5.5 mg, 3 times / month Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed or refractory light-chain (AL) amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
DLT: Diarrhea, Renal failure... Dose limiting toxicities: Diarrhea (grade 3, 1 patient) Sources: Renal failure (grade 2, 1 patient) Failure respiratory (grade 2, 1 patient) |
4 mg 3 times / month multiple, oral MTD|RP2D|Recommended Dose: 4 mg, 3 times / month Route: oral Route: multiple Dose: 4 mg, 3 times / month Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 6 Health Status: unhealthy Condition: relapsed or refractory light-chain (AL) amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 6 Sources: |
DLT: Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 3, 1 patient) Sources: |
2.34 mg/m2 3 times / month multiple, intravenous MTD Dose: 2.34 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 2.34 mg/m2, 3 times / month Sources: |
unhealthy, 69.5 years (range: 47–75 years) n = 10 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 69.5 years (range: 47–75 years) Sex: M+F Population Size: 10 Sources: |
DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 3, 1 patient) Sources: |
3.95 mg/m2 1 times / week multiple, oral Highest studied dose Dose: 3.95 mg/m2, 1 times / week Route: oral Route: multiple Dose: 3.95 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) n = 4 Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Population Size: 4 Sources: |
DLT: Nausea, Vomiting... Dose limiting toxicities: Nausea (grade 3, 1 patient) Sources: Vomiting (grade 3, 1 patient) Diarrhea (grade 3, 1 patient) Erythema multiforme (grade 3, 1 patient) |
2.97 mg/m2 1 times / week multiple, oral MTD Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Sources: |
DLT: Nausea, Vomiting... Dose limiting toxicities: Nausea (grade 3, 1 patient) Sources: Vomiting (grade 3, 1 patient) Diarrhea (grade 3, 1 patient) |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Other AEs: Upper respiratory tract infection, Upper respiratory tract infection... Other AEs: Upper respiratory tract infection (grade 1-2, 19%) Sources: Upper respiratory tract infection (grade 3, <1%) Peripheral neuropathies (grade 1-2, 28%) Peripheral neuropathies (grade 3, 2%) Diarrhea (grade 1-2, 42%) Diarrhea (grade 3, 6%) Constipation (grade 1-2, 34%) Constipation (grade 3, <1%) Nausea (grade 1-2, 26%) Nausea (grade 3, 2%) Vomiting (grade 1-2, 22%) Vomiting (grade 3, 1%) Rash (grade 1-2, 19%) Rash (grade 3, 3%) Back pain (grade 1-2, 21%) Back pain (grade 3, <1%) Edema peripheral (grade 1-2, 25%) Edema peripheral (grade 3, 2%) Thrombocytopenia (grade 1-2, 78%) Thrombocytopenia (grade 3, 26%) Neutropenia (grade 1-2, 67%) Neutropenia (grade 3, 26%) Blurred vision (all grades, 3%) Dry eye (5%) Conjunctivitis (6%) |
4 mg 1 times / week multiple, oral MTD Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 6 Health Status: unhealthy Condition: relapsed/refractory AL amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 6 Sources: |
DLT: Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 3, 1 patient) Sources: |
5.5 mg 1 times / week multiple, oral Dose: 5.5 mg, 1 times / week Route: oral Route: multiple Dose: 5.5 mg, 1 times / week Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed/refractory AL amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
DLT: Diarrhea, Renal failure... Dose limiting toxicities: Diarrhea (grade 3, 1 patient) Sources: Renal failure (grade 2, 1 patient) Dyspnea (grade 2, 1 patient) |
2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
Disc. AE: Thrombocytopenia, Diarrhea... Other AEs: Renal failure... AEs leading to discontinuation/dose reduction: Thrombocytopenia (1 patient) Other AEs:Diarrhea (1 patient) Nausea and vomiting (1 patient) Hypercalcemia (1 patient) Dyspnea (1 patient) Renal failure (2 patients) Sources: Page: C16005 |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 55dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 55 |
Disc. AE: Diarrhea, Fatigue... AEs leading to discontinuation/dose reduction: Diarrhea Sources: Page: p. 55Fatigue (0.8%) Asthenia (0.8%) Peripheral sensory neuropathy (0.6%) Septic shock (0.6%) |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 56dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 56 |
Disc. AE: Thrombocytopenia... AEs leading to discontinuation/dose reduction: Thrombocytopenia (8.6%) Sources: Page: p. 56 |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Neutropenia | grade 4, 1 patient DLT |
1.76 mg/m2 3 times / month multiple, intravenous Dose: 1.76 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 1.76 mg/m2, 3 times / month Sources: |
unhealthy, 45 years (range: 23–73 years) n = 7 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 45 years (range: 23–73 years) Sex: M+F Population Size: 7 Sources: |
| Fatigue | grade 2, 1 patient DLT |
3.11 mg/m2 3 times / month multiple, intravenous Highest studied dose Dose: 3.11 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 3.11 mg/m2, 3 times / month Sources: |
unhealthy, 56 years (range: 27–72 years) n = 5 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 56 years (range: 27–72 years) Sex: M+F Population Size: 5 Sources: |
| Nausea | grade 2, 1 patient DLT |
3.11 mg/m2 3 times / month multiple, intravenous Highest studied dose Dose: 3.11 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 3.11 mg/m2, 3 times / month Sources: |
unhealthy, 56 years (range: 27–72 years) n = 5 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 56 years (range: 27–72 years) Sex: M+F Population Size: 5 Sources: |
| Diarrhea | grade 2-3, 2 patients DLT |
3.11 mg/m2 3 times / month multiple, intravenous Highest studied dose Dose: 3.11 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 3.11 mg/m2, 3 times / month Sources: |
unhealthy, 56 years (range: 27–72 years) n = 5 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 56 years (range: 27–72 years) Sex: M+F Population Size: 5 Sources: |
| Vomiting | grade 2-3, 2 patients DLT |
3.11 mg/m2 3 times / month multiple, intravenous Highest studied dose Dose: 3.11 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 3.11 mg/m2, 3 times / month Sources: |
unhealthy, 56 years (range: 27–72 years) n = 5 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 56 years (range: 27–72 years) Sex: M+F Population Size: 5 Sources: |
| Acute renal failure | grade 3, 1 patient DLT |
3.11 mg/m2 3 times / month multiple, intravenous Highest studied dose Dose: 3.11 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 3.11 mg/m2, 3 times / month Sources: |
unhealthy, 56 years (range: 27–72 years) n = 5 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 56 years (range: 27–72 years) Sex: M+F Population Size: 5 Sources: |
| Failure respiratory | grade 2, 1 patient DLT, Disc. AE |
5.5 mg 3 times / month multiple, oral Highest studied dose Dose: 5.5 mg, 3 times / month Route: oral Route: multiple Dose: 5.5 mg, 3 times / month Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed or refractory light-chain (AL) amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
| Renal failure | grade 2, 1 patient DLT, Disc. AE |
5.5 mg 3 times / month multiple, oral Highest studied dose Dose: 5.5 mg, 3 times / month Route: oral Route: multiple Dose: 5.5 mg, 3 times / month Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed or refractory light-chain (AL) amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
| Diarrhea | grade 3, 1 patient DLT |
5.5 mg 3 times / month multiple, oral Highest studied dose Dose: 5.5 mg, 3 times / month Route: oral Route: multiple Dose: 5.5 mg, 3 times / month Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed or refractory light-chain (AL) amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
| Thrombocytopenia | grade 3, 1 patient DLT, Disc. AE |
4 mg 3 times / month multiple, oral MTD|RP2D|Recommended Dose: 4 mg, 3 times / month Route: oral Route: multiple Dose: 4 mg, 3 times / month Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 6 Health Status: unhealthy Condition: relapsed or refractory light-chain (AL) amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 6 Sources: |
| Neutropenia | grade 3, 1 patient DLT |
2.34 mg/m2 3 times / month multiple, intravenous MTD Dose: 2.34 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 2.34 mg/m2, 3 times / month Sources: |
unhealthy, 69.5 years (range: 47–75 years) n = 10 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 69.5 years (range: 47–75 years) Sex: M+F Population Size: 10 Sources: |
| Diarrhea | grade 3, 1 patient DLT, Disc. AE |
3.95 mg/m2 1 times / week multiple, oral Highest studied dose Dose: 3.95 mg/m2, 1 times / week Route: oral Route: multiple Dose: 3.95 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) n = 4 Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Population Size: 4 Sources: |
| Erythema multiforme | grade 3, 1 patient DLT, Disc. AE |
3.95 mg/m2 1 times / week multiple, oral Highest studied dose Dose: 3.95 mg/m2, 1 times / week Route: oral Route: multiple Dose: 3.95 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) n = 4 Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Population Size: 4 Sources: |
| Nausea | grade 3, 1 patient DLT, Disc. AE |
3.95 mg/m2 1 times / week multiple, oral Highest studied dose Dose: 3.95 mg/m2, 1 times / week Route: oral Route: multiple Dose: 3.95 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) n = 4 Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Population Size: 4 Sources: |
| Vomiting | grade 3, 1 patient DLT, Disc. AE |
3.95 mg/m2 1 times / week multiple, oral Highest studied dose Dose: 3.95 mg/m2, 1 times / week Route: oral Route: multiple Dose: 3.95 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) n = 4 Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Population Size: 4 Sources: |
| Diarrhea | grade 3, 1 patient DLT, Disc. AE |
2.97 mg/m2 1 times / week multiple, oral MTD Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Sources: |
| Nausea | grade 3, 1 patient DLT, Disc. AE |
2.97 mg/m2 1 times / week multiple, oral MTD Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Sources: |
| Vomiting | grade 3, 1 patient DLT, Disc. AE |
2.97 mg/m2 1 times / week multiple, oral MTD Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Sources: |
| Dry eye | 5% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Conjunctivitis | 6% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Blurred vision | all grades, 3% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Rash | grade 1-2, 19% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Upper respiratory tract infection | grade 1-2, 19% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Back pain | grade 1-2, 21% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Vomiting | grade 1-2, 22% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Edema peripheral | grade 1-2, 25% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Nausea | grade 1-2, 26% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Peripheral neuropathies | grade 1-2, 28% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Constipation | grade 1-2, 34% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Diarrhea | grade 1-2, 42% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Neutropenia | grade 1-2, 67% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Thrombocytopenia | grade 1-2, 78% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Vomiting | grade 3, 1% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Edema peripheral | grade 3, 2% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Nausea | grade 3, 2% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Peripheral neuropathies | grade 3, 2% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Neutropenia | grade 3, 26% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Thrombocytopenia | grade 3, 26% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Rash | grade 3, 3% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Diarrhea | grade 3, 6% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Back pain | grade 3, <1% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Constipation | grade 3, <1% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Upper respiratory tract infection | grade 3, <1% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
| Thrombocytopenia | grade 3, 1 patient DLT, Disc. AE |
4 mg 1 times / week multiple, oral MTD Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 6 Health Status: unhealthy Condition: relapsed/refractory AL amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 6 Sources: |
| Dyspnea | grade 2, 1 patient DLT |
5.5 mg 1 times / week multiple, oral Dose: 5.5 mg, 1 times / week Route: oral Route: multiple Dose: 5.5 mg, 1 times / week Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed/refractory AL amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
| Renal failure | grade 2, 1 patient DLT |
5.5 mg 1 times / week multiple, oral Dose: 5.5 mg, 1 times / week Route: oral Route: multiple Dose: 5.5 mg, 1 times / week Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed/refractory AL amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
| Diarrhea | grade 3, 1 patient DLT, Disc. AE |
5.5 mg 1 times / week multiple, oral Dose: 5.5 mg, 1 times / week Route: oral Route: multiple Dose: 5.5 mg, 1 times / week Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed/refractory AL amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
| Diarrhea | 1 patient Disc. AE |
2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
| Dyspnea | 1 patient Disc. AE |
2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
| Hypercalcemia | 1 patient Disc. AE |
2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
| Nausea and vomiting | 1 patient Disc. AE |
2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
| Thrombocytopenia | 1 patient Disc. AE |
2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
| Renal failure | 2 patients | 2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
| Peripheral sensory neuropathy | 0.6% Disc. AE |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 55dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 55 |
| Septic shock | 0.6% Disc. AE |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 55dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 55 |
| Asthenia | 0.8% Disc. AE |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 55dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 55 |
| Fatigue | 0.8% Disc. AE |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 55dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 55 |
| Diarrhea | Disc. AE | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 55dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 55 |
| Thrombocytopenia | 8.6% Disc. AE |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 56dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 56 |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| major | ||||
| minor | ||||
| minor | ||||
| minor | ||||
| minor | ||||
| no | ||||
| weak | ||||
| yes | unlikely Comment: Smoking is known to be a moderate CYP1A2 inducer. Based on population PK analyses of smokers in the Phase 3 Study C16010, smoking status (n=33 current smokers) was not found to be a significant covariate affecting ixazomib PK Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208462Orig1s000ClinPharmR.pdf#page=8 Page: 8.0 |
|||
| yes | yes (co-administration study) Comment: Clinical DDI studies with strong CYP3A4 inhibitors ketoconazole and clarithromycin did not show clinically meaningful effects on ixazomib systemic exposure. On the other hand, clinical study with the strong CYP3A4 inducer rifampin showed significant decrease in ixazomib exposure (AUC v74%, CMAX |54%). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208462Orig1s000ClinPharmR.pdf#page=5 Page: 5.0 |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma. | 2007 Apr |
|
| Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. | 2010 Mar 1 |
|
| An evidence-based review of ixazomib citrate and its potential in the treatment of newly diagnosed multiple myeloma. | 2014 |
|
| Ixazomib for the treatment of multiple myeloma. | 2015 |
|
| The investigational proteasome inhibitor ixazomib for the treatment of multiple myeloma. | 2015 |
|
| Therapeutic landscape of carfilzomib and other modulators of the ubiquitin-proteasome pathway. | 2015 Mar 1 |
Patents
Sample Use Guides
Recommended starting dose of 4 mg taken orally on Days 1, 8, and 15 of a 28-day cycle.
Route of Administration:
Oral
In a cell viability assay, MM.1S {Dexamethasone-(Dex) sensitive}, MM.1R (Dex-resistant), RPMI-8226, OPM1, OPM2, H929 and INA-6 (IL-6-dependent) human multiple myeloma cell lines were treated with various concentrations of ixazomib (6.25, 12.5, 25, 50 nM) for 48h. The anti-myeloma activity of the drug was observed in MM cell lines sensitive and resistant to conventional therapies, as well as representing distinct cytogenetic profiles.
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NCI_THESAURUS |
C2160
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WHO-ATC |
L01XX50
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NDF-RT |
N0000175604
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EU-Orphan Drug |
EU/3/12/1060
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admin on Thu Jul 06 01:32:16 UTC 2023 , Edited by admin on Thu Jul 06 01:32:16 UTC 2023
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5067
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25183872
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1072833-77-2
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Ixazomib
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1723735
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C97940
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100000144580
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DB09570
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SUB121332
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71050168A2
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71050168A2
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90942
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Ixazomib
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9411
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DTXSID701025662
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M11904
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YY-46
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