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Details

Stereochemistry ABSOLUTE
Molecular Formula C14H19BCl2N2O4
Molecular Weight 361.0291
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])(B(O)O)N=C(CN=C(c1cc(ccc1Cl)Cl)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 361.0291
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 (MLN2238) is an active metabolite of orally bioavailable proteasome inhibitor ixazomib citrate (MLN9708), which hydrolyzes upon administration. Ixazomib citrate was approved under the name Ninlaro for the treatment of multiple myeloma in patients who have received at least one prior therapy. In vitro studies has shown that ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.

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

1.44797755E12
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

1.44797755E12
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

1.44797755E12
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

1.44797755E12
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
Intracellular protein degradation: from a vague idea, through the lysosome and the ubiquitin-proteasome system, and onto human diseases and drug targeting (Nobel lecture).
2005 Sep 19
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. Dose should be taken at least one hour before or at least two hours after food.
Route of Administration: Oral
Osteoblasts were generated from mesenchymal osteoprogenitors by culture in osteogenic medium (containing 5 mmol/L b-glycerophosphate, 50 mkg/mL ascorbic acid, and 80 nmol/L dexamethasone). Mesenchymal stem cell (MSC, passage 2–3) or the hMSC–TERT cell line were exposed to different MLN2238 or bortezomib concentrations and cultured in osteogenic medium for 11 or 21 days for alkaline phosphatase (ALP) activity and matrix mineralization assays, respectively. ALP activity was quantified by hydrolysis of p-nitrophenylphosphate into p-nitrophenol (Sigma-Aldrich), whereas mineralization was assessed by quantitative measurement of Alizarin Red staining.
Substance Class Chemical
Created
by admin
on Sat Jun 26 07:45:12 UTC 2021
Edited
by admin
on Sat Jun 26 07:45:12 UTC 2021
Record UNII
71050168A2
Record Status Validated (UNII)
Record Version
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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
IXAZOMIB [WHO-DD]
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 [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 Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
WHO-ATC L01XX50
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
NDF-RT N0000175604
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
EU-Orphan Drug EU/3/12/1060
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
Code System Code Type Description
DRUG CENTRAL
5067
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
PRIMARY
PUBCHEM
25183872
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
PRIMARY
CAS
1072833-77-2
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
PRIMARY
LACTMED
Ixazomib
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
PRIMARY
RXCUI
1723735
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C97940
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
PRIMARY
DRUG BANK
DB09570
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
PRIMARY
EVMPD
SUB121332
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
PRIMARY
FDA UNII
71050168A2
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
PRIMARY
WIKIPEDIA
Ixazomib
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
PRIMARY
INN
9411
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
PRIMARY
MERCK INDEX
M11904
Created by admin on Sat Jun 26 07:45:12 UTC 2021 , Edited by admin on Sat Jun 26 07:45:12 UTC 2021
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