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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
Structure of IXAZOMIB

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

HIDE SMILES / InChI

Molecular Formula C14H19BCl2N2O4
Molecular Weight 361.029
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
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

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

Targets

Primary TargetPharmacologyConditionPotency
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

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NINLARO

Approved Use

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 Date

2015
Primary
NINLARO

Approved Use

INDICATIONS 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 Date

2015
Primary
NINLARO

Approved Use

INDICATIONS 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 Date

2015
Primary
NINLARO

Approved Use

INDICATIONS 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 Date

2015
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
77 ng/mL
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
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
1470 ng × h/mL
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
144.69 h
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
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
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
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
multiple, oral
IXAZOMIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
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

Doses

DosePopulationAdverse 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)
Diarrhea (grade 2-3, 2 patients)
Vomiting (grade 2-3, 2 patients)
Fatigue (grade 2, 1 patient)
Nausea (grade 2, 1 patient)
Sources:
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)
Renal failure (grade 2, 1 patient)
Failure respiratory (grade 2, 1 patient)
Sources:
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)
Vomiting (grade 3, 1 patient)
Diarrhea (grade 3, 1 patient)
Erythema multiforme (grade 3, 1 patient)
Sources:
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)
Vomiting (grade 3, 1 patient)
Diarrhea (grade 3, 1 patient)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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%)
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%)
Sources:
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)
Renal failure (grade 2, 1 patient)
Dyspnea (grade 2, 1 patient)
Sources:
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)
dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22)
Sources: Page: C16005
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)
Diarrhea (1 patient)
Nausea and vomiting (1 patient)
Hypercalcemia (1 patient)
Dyspnea (1 patient)
Other AEs:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources: Page: p. 55
unhealthy
n = 360
Health Status: unhealthy
Population Size: 360
Sources: Page: p. 55
Disc. AE: Diarrhea, Fatigue...
AEs leading to
discontinuation/dose reduction:
Diarrhea
Fatigue (0.8%)
Asthenia (0.8%)
Peripheral sensory neuropathy (0.6%)
Septic shock (0.6%)
Sources: Page: p. 55
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources: Page: p. 56
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

AEs

AESignificanceDosePopulation
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources:
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)
dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22)
Sources: Page: C16005
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)
dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22)
Sources: Page: C16005
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)
dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22)
Sources: Page: C16005
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)
dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22)
Sources: Page: C16005
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)
dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22)
Sources: Page: C16005
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)
dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22)
Sources: Page: C16005
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources: Page: p. 55
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources: Page: p. 55
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources: Page: p. 55
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources: Page: p. 55
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources: Page: p. 55
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)
dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle)
Sources: Page: p. 56
unhealthy
n = 360
Health Status: unhealthy
Population Size: 360
Sources: Page: p. 56
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical 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

Drug as victim

TargetModalityActivityMetaboliteClinical 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
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%).
Page: 5.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
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
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 18:17:41 GMT 2023
Edited
by admin
on Fri Dec 15 18:17:41 GMT 2023
Record UNII
71050168A2
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
IXAZOMIB
DASH   INN   USAN   WHO-DD  
USAN   INN  
Official Name English
IXAZOMIB [MI]
Common Name English
MLN2238
Code English
IXAZOMIB [USAN]
Common Name English
MLN-9708 FREE BASE
Code English
MLN-2238
Code English
((1R)-1-((2,5-DICHLOROBENZAMIDO)ACETAMIDO)-3-METHYLBUTYL)BORONIC ACID
Systematic Name English
Ixazomib [WHO-DD]
Common Name English
ixazomib [INN]
Common Name English
BORONIC ACID, B-((1R)-1-((2-((2,5-DICHLOROBENZOYL)AMINO)ACETYL)AMINO)-3-METHYLBUTYL)-
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2160
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
WHO-ATC L01XX50
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
NDF-RT N0000175604
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
EU-Orphan Drug EU/3/12/1060
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
Code System Code Type Description
DRUG CENTRAL
5067
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
PUBCHEM
25183872
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
CAS
1072833-77-2
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
LACTMED
Ixazomib
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
RXCUI
1723735
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY RxNorm
NCI_THESAURUS
C97940
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
SMS_ID
100000144580
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
DRUG BANK
DB09570
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
EVMPD
SUB121332
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
FDA UNII
71050168A2
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
DAILYMED
71050168A2
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
CHEBI
90942
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
WIKIPEDIA
Ixazomib
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
INN
9411
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
EPA CompTox
DTXSID701025662
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
MERCK INDEX
m11904
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
USAN
YY-46
Created by admin on Fri Dec 15 18:17:41 GMT 2023 , Edited by admin on Fri Dec 15 18:17:41 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
CYP 1A2 CONTRIBUTES FOR 26% OF IXAZOMIB METABOLISM
METABOLIC ENZYME -> SUBSTRATE
At higher than clinical concentrations, ixazomib was metabolized by multiple CYP isoforms with estimated relative contributions of 3A4 (42%), 1A2 (26%), 2B6 (16%), 2C8 (6%), 2D6 (5%), 2C19 (5%) and 2C9 (< 1%).
EXCRETED UNCHANGED
62% of the 4.1 MG dose recovered in the urine (3.3% as unchanged drug)
AMOUNT EXCRETED
URINE
METABOLIC ENZYME -> SUBSTRATE
At higher than clinical concentrations, ixazomib was metabolized by multiple CYP isoforms with estimated relative contributions of 3A4 (42%), 1A2 (26%), 2B6 (16%), 2C8 (6%), 2D6 (5%), 2C19 (5%) and 2C9 (< 1%).
METABOLIC ENZYME -> SUBSTRATE
At higher than clinical concentrations, ixazomib was metabolized by multiple CYP isoforms with estimated relative contributions of 3A4 (42%), 1A2 (26%), 2B6 (16%), 2C8 (6%), 2D6 (5%), 2C19 (5%) and 2C9 (< 1%).
METABOLIC ENZYME -> SUBSTRATE
At higher than clinical concentrations, ixazomib was metabolized by multiple CYP isoforms with estimated relative contributions of 3A4 (42%), 1A2 (26%), 2B6 (16%), 2C8 (6%), 2D6 (5%), 2C19 (5%) and 2C9 (< 1%).
METABOLIC ENZYME -> SUBSTRATE
CYP 3A CONTRIBUTES FOR 42% OF IXAZOMIB METABOLISM
MAJOR
METABOLIC ENZYME -> SUBSTRATE
CYP 2B6 CONTRIBUTES FOR 16% OF IXAZOMIB METABOLISM
BINDER->LIGAND
BINDING
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC