Pharmacokinetic Study of Oral IXAZOMIB in Cancer Patients With Liver Dysfunction
Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01912222
Collaborator
(none)
48
4
3
19
12
0.6
Study Details
Study Description
Brief Summary
This is a phase 1, 2-part, pharmacokinetic study in patients with advanced solid tumors or hematologic malignancies and varying degrees of liver dysfunction (normal function, moderate hepatic impairement or severe hepatic impairment) as defined by the National Cancer Institute (NCI) Organ Dysfunction Working Group.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
48 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Pharmacokinetic Study of Oral IXAZOMIB (MLN9708) in Patients With Advanced Solid Tumors or Hematologic Malignancies With Varying Degrees of Liver Dysfunction
Study Start Date
:
Aug 1, 2013
Actual Primary Completion Date
:
Mar 1, 2015
Actual Study Completion Date
:
Mar 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IXAZOMIB Arm 1 Experimental: Arm 1 (Normal hepatic function) In the 15 day period that constitutes Part A of the trial, patients will receive a single oral 4 mg dose of IXAZOMIB capsule on Day 1. Patients from Part A will then have the option of continuing the study by participating in Part B, starting immediately after Part A, where they will receive IXAZOMIB on Days 1, 8, and 15 of a 28-day cycle |
Drug: IXAZOMIB
|
| Experimental: IXAZOMIB Arm 2 Experimental: Arm 2 (Moderate hepatic impairment) In the 15 day period that constitutes Part A of the trial, patients will receive a single oral 2.3 mg dose of IXAZOMIB capsule on Day 1. Patients from Part A will then have the option of continuing the study by participating in Part B, starting immediately after Part A, where they will receive IXAZOMIB on Days 1, 8, and 15 of a 28-day cycle |
Drug: IXAZOMIB
|
| Experimental: IXAZOMIB Arm 3 Experimental: Arm 3 (Severe hepatic impairment) In the 15 day period that constitutes Part A of the trial, patients will receive a single oral 1.5 mg dose of IXAZOMIB capsule on Day 1. Patients from Part A will then have the option of continuing the study by participating in Part B, starting immediately after Part A, where they will receive IXAZOMIB on Days 1, 8, and 15 of a 28-day cycle |
Drug: IXAZOMIB
|
Outcome Measures
Primary Outcome Measures
- Unbound AUC(0-last): Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib [Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose]
- Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib [Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose]
- Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib [Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose]
- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) [Baseline up to 30 days after last dose of study drug (Day 45 for each treatment cycle for up to a maximum of 12 cycles [28 days treatment cycles])]
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
- Number of Participants Reporting Clinically Significant Change From Baseline in Laboratory Values [Baseline up to Day 15 for each treatment cycle (28 days treatment cycle for up to a maximum of 12 cycles)]
The number of participants with any markedly abnormal standard safety laboratory values collected throughout study.
- Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs [Baseline up to Day 15 for each treatment cycle (28 days treatment cycle for up to a maximum of 12 cycles)]
Vital signs included body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
18 years or older
-
Patients must have a diagnosis of an advanced malignant solid tumor or hematologic malignancy for which standard, curative, or life-prolonging treatment does not exist or is no longer effective
-
Total bilirubin and aspartate aminotransferase (AST) levels consistent with normal hepatic function (total bilirubin and AST ≤ the upper limit of normal), moderate hepatic impairment (total bilirubin > 1.5 to 3x the upper limit of normal with any AST level) or severe hepatic impairment (total bilirubin > 3x the upper limit of normal with any AST level)
-
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
-
Female patients who are postmenopausal for at least 1 year OR are surgically sterile OR if of childbearing potential, agree to practice 2 effective methods of contraception at the same time during the entire study through 90 days after the last dose of study drug OR agree to practice true abstinence
-
Male patients who agree to practice effective barrier contraception during the entire study and through 90 days after the last dose of study drug OR agree to practice true abstinence
-
Voluntary written consent
-
Suitable venous access for the conduct of blood sampling
-
Appropriate clinical laboratory values as specified in the protocol
Exclusion Criteria:
-
Systemic treatment with strong and moderate inhibitors of CYP1A2, strong and moderate inhibitors of CYP3A, or clinically significant CYP3A inducers or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study drug
-
Use of any nicotine-containing products within 14 days before the first dose of study drug
-
Central Nervous System Involvement or Symptomatic brain metastasis. Patients with brain metastases: must have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks after completion of the definitive therapy; and must be without neurologic dysfunction that would confound the evaluation of neurologic and other AEs
-
Female patients who are lactating or breastfeeding or have a positive serum pregnancy test
-
Serious medical or psychiatric illness that could interfere with participation in the study
-
Treatment with any investigational products or radiotherapy within 21 days before the first dose of study drug
-
Systemic anticancer therapy within 14 days before the first dose of study drug
-
Exposure to nitrosoureas or mitomycin C within 6 weeks before the first dose of study drug
-
Treatment with therapeutic monoclonal antibodies or antibody-drug conjugates within 60 days before the first dose of study drug
-
Radiotherapy or major surgery within the 14 days preceding the first dose of study drug
-
Infection requiring systemic intravenous antibiotic therapy or other serious infection within 14 days before the first dose of study drug
-
Life-threatening illness unrelated to cancer
-
Severe CNS, pulmonary, or renal disease not related to the patient's cancer
-
Known human immunodeficiency virus (HIV) positive
-
Evidence of uncontrolled cardiovascular conditions
-
QTc > 500 milliseconds (msec) on a 12-lead ECG obtained during the Screening period
-
Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of IXAZOMIB
-
Known allergy to the study medication, its analogues, or excipients in the formulation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fairway | Kansas | United States | ||
| 2 | Cleveland | Ohio | United States | ||
| 3 | Dallas | Texas | United States | ||
| 4 | Houston | Texas | United States |
Sponsors and Collaborators
- Millennium Pharmaceuticals, Inc.
Investigators
- Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01912222
Other Study ID Numbers:
- C16018
- U1111-1177-7929
First Posted:
Jul 31, 2013
Last Update Posted:
Jun 2, 2016
Last Verified:
Feb 1, 2016
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 4 investigative sites in the United States from 27 August 2013 to 25 March 2015. |
|---|---|
| Pre-assignment Detail | Participants with diagnosis of advanced solid tumors or hematologic malignancies having varying degrees of liver dysfunction enrolled in 1 of 3 treatment groups to receive ixazomib 4 mg (normal hepatic function), 2.3 mg (moderate impairment), 1.5 mg (severe impairment) on Day 1 (Part A, 15 day cycle) and on Days 1,8 and 15(Part B, 28 day cycle). |
| Arm/Group Title | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|
| Arm/Group Description | Ixazomib 4 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with normal hepatic function. | Ixazomib 2.3 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with moderate hepatic impairment. | Ixazomib 1.5 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with severe hepatic impairment. |
| Period Title: Part A: Pharmacokinetic Period | |||
| STARTED | 13 | 15 | 20 |
| COMPLETED | 12 | 13 | 18 |
| NOT COMPLETED | 1 | 2 | 2 |
| Period Title: Part A: Pharmacokinetic Period | |||
| STARTED | 13 | 15 | 20 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 13 | 15 | 20 |
Baseline Characteristics
| Arm/Group Title | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) | Total |
|---|---|---|---|---|
| Arm/Group Description | Ixazomib 4 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with normal hepatic function. | Ixazomib 2.3 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with moderate hepatic impairment. | Ixazomib 1.5 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with severe hepatic impairment. | Total of all reporting groups |
| Overall Participants | 13 | 15 | 20 | 48 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
58.8
(15.19)
|
56.2
(15.26)
|
54.5
(13.84)
|
56.2
(14.45)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
7
53.8%
|
7
46.7%
|
6
30%
|
20
41.7%
|
| Male |
6
46.2%
|
8
53.3%
|
14
70%
|
28
58.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
4
26.7%
|
0
0%
|
4
8.3%
|
| Not Hispanic or Latino |
10
76.9%
|
9
60%
|
20
100%
|
39
81.3%
|
| Unknown or Not Reported |
3
23.1%
|
2
13.3%
|
0
0%
|
5
10.4%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||
| White |
11
84.6%
|
8
53.3%
|
13
65%
|
32
66.7%
|
| Black or African American |
2
15.4%
|
2
13.3%
|
6
30%
|
10
20.8%
|
| Other |
0
0%
|
4
26.7%
|
0
0%
|
4
8.3%
|
| Asian |
0
0%
|
1
6.7%
|
1
5%
|
2
4.2%
|
| Height (centimeter (cm)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [centimeter (cm)] |
168.6
(6.79)
|
168.6
(12.56)
|
169.6
(27.54)
|
169.0
(19.01)
|
| Weight (kilogram (kg)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kilogram (kg)] |
74.42
(16.788)
|
76.97
(12.050)
|
76.94
(23.498)
|
76.27
(18.431)
|
| Disease type at diagnosis (participants) [Number] | ||||
| Solid tumor |
10
76.9%
|
14
93.3%
|
18
90%
|
42
87.5%
|
| Other |
3
23.1%
|
1
6.7%
|
2
10%
|
6
12.5%
|
| Months from initial diagnosis to first dose of ixazomib (months) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [months] |
56.5
(43.40)
|
23.7
(16.59)
|
35.2
(28.73)
|
37.4
(32.56)
|
| Participants with prior antineoplastic therapy (participants) [Number] | ||||
| Number [participants] |
13
100%
|
15
100%
|
20
100%
|
48
100%
|
| Participant with prior radiation (participants) [Number] | ||||
| Had prior radiation |
6
46.2%
|
6
40%
|
11
55%
|
23
47.9%
|
| Had no prior radiation |
7
53.8%
|
9
60%
|
9
45%
|
25
52.1%
|
| Participant with prior surgery (participants) [Number] | ||||
| Had prior surgery |
12
92.3%
|
14
93.3%
|
18
90%
|
44
91.7%
|
| Had no prior surgery |
1
7.7%
|
1
6.7%
|
2
10%
|
4
8.3%
|
| Baseline Eastern Cooperative Oncology Group (ECOG) performance status (participants) [Number] | ||||
| 0 |
1
7.7%
|
0
0%
|
1
5%
|
2
4.2%
|
| 1 |
12
92.3%
|
15
100%
|
19
95%
|
46
95.8%
|
| Baseline total bilirubin (micro mole per liter (mcmol/L)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [micro mole per liter (mcmol/L)] |
7.43
(3.092)
|
40.25
(5.594)
|
108.61
(78.372)
|
59.85
(66.249)
|
| Baseline aspartate aminotransferase (AST) (units per liter (U/L)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [units per liter (U/L)] |
21.04
(6.884)
|
169.97
(147.433)
|
197.48
(198.211)
|
141.09
(167.256)
|
Outcome Measures
| Title | Unbound AUC(0-last): Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib |
|---|---|
| Description | |
| Time Frame | Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis population was defined as participants who received the single dose of ixazomib in Part A of the study, did not receive any excluded concomitant medications through the completion of PK sampling, and had sufficient concentration-time data to permit the reliable estimation of PK parameters by noncompartmental analysis methods. |
| Arm/Group Title | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|
| Arm/Group Description | Ixazomib 4 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with normal hepatic function.. | Ixazomib 2.3 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with moderate hepatic impairment. | Ixazomib 1.5 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with severe hepatic impairment. |
| Measure Participants | 12 | 10 | 11 |
| Geometric Mean (Standard Deviation) [nanogram*hours per milliliter (ng*hr/mL)] |
9.6476
(5.39885)
|
7.3292
(5.35269)
|
4.4383
(4.21266)
|
| Title | Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib |
|---|---|
| Description | |
| Time Frame | Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis population was defined as participants who received the single dose of ixazomib in Part A of the study, did not receive any excluded concomitant medications through the completion of PK sampling, and had sufficient concentration-time data to permit the reliable estimation of PK parameters by noncompartmental analysis methods. |
| Arm/Group Title | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|
| Arm/Group Description | Ixazomib 4 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with normal hepatic function. | Ixazomib 2.3 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with moderate hepatic impairment. | Ixazomib 1.5 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with severe hepatic impairment. |
| Measure Participants | 12 | 13 | 18 |
| Geometric Mean (Standard Deviation) [nanogram per milliliter (ng/mL)] |
0.50893
(0.271928)
|
0.37245
(0.385113)
|
0.23176
(0.271358)
|
| Title | Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib |
|---|---|
| Description | |
| Time Frame | Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis population was defined as participants who received the single dose of ixazomib in Part A of the study, did not receive any excluded concomitant medications through the completion of PK sampling, and had sufficient concentration-time data to permit the reliable estimation of PK parameters by noncompartmental analysis methods. |
| Arm/Group Title | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|
| Arm/Group Description | Ixazomib 4 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with normal hepatic function. | Ixazomib 2.3 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with moderate hepatic impairment. | Ixazomib 1.5 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with severe hepatic impairment. |
| Measure Participants | 12 | 13 | 18 |
| Median (Full Range) [hours] |
0.950
|
1.500
|
1.205
|
| Title | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) |
|---|---|
| Description | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
| Time Frame | Baseline up to 30 days after last dose of study drug (Day 45 for each treatment cycle for up to a maximum of 12 cycles [28 days treatment cycles]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis population was defined as participants who received at least 1 dose of ixazomib. |
| Arm/Group Title | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|
| Arm/Group Description | Ixazomib 4 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with normal hepatic function. | Ixazomib 2.3 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with moderate hepatic impairment. | Ixazomib 1.5 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with severe hepatic impairment. |
| Measure Participants | 13 | 15 | 20 |
| TEAE |
13
100%
|
15
100%
|
20
100%
|
| SAE |
6
46.2%
|
10
66.7%
|
15
75%
|
| Title | Number of Participants Reporting Clinically Significant Change From Baseline in Laboratory Values |
|---|---|
| Description | The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. |
| Time Frame | Baseline up to Day 15 for each treatment cycle (28 days treatment cycle for up to a maximum of 12 cycles) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis population was defined as participants who received at least 1 dose of ixazomib. |
| Arm/Group Title | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|
| Arm/Group Description | Ixazomib 4 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with normal hepatic function. | Ixazomib 2.3 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with moderate hepatic impairment. | Ixazomib 1.5 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with severe hepatic impairment. |
| Measure Participants | 13 | 15 | 20 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs |
|---|---|
| Description | Vital signs included body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm). |
| Time Frame | Baseline up to Day 15 for each treatment cycle (28 days treatment cycle for up to a maximum of 12 cycles) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis population was defined as participants who received at least 1 dose of ixazomib. |
| Arm/Group Title | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|
| Arm/Group Description | Ixazomib 4 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with normal hepatic function. | Ixazomib 2.3 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with moderate hepatic impairment. | Ixazomib 1.5 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with severe hepatic impairment. |
| Measure Participants | 13 | 15 | 20 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (up to cycle 12 [each cycle is 28 days]). | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||||
| Arm/Group Title | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) | |||
| Arm/Group Description | Ixazomib 4 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with normal hepatic function.. | Ixazomib 2.3 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with moderate hepatic impairment. | Ixazomib 1.5 mg, capsule, orally, on Day 1 in the pharmacokinetic part (Part A, 15-day cycle) and once on Days 1, 8 and 15 in the 28 day treatment cycle part (Part B) in participants with severe hepatic impairment. | |||
All Cause Mortality |
||||||
| Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/13 (46.2%) | 10/15 (66.7%) | 15/20 (75%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Abdominal pain upper | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Nausea | 1/13 (7.7%) | 0/15 (0%) | 1/20 (5%) | |||
| Vomiting | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Ascites | 0/13 (0%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Peritoneal haemorrhage | 0/13 (0%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Intestinal obstruction | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Rectal haemorrhage | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Oesophageal ulcer | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| General disorders | ||||||
| Asthenia | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Fatigue | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Axillary pain | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Pain | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Pyrexia | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Hepatobiliary disorders | ||||||
| Hepatic failure | 0/13 (0%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Acute hepatic failure | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Hyperbilirubinaemia | 0/13 (0%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Cholangitis | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Infections and infestations | ||||||
| Device related infection | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Pneumonia | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Septic shock | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 1/13 (7.7%) | 0/15 (0%) | 1/20 (5%) | |||
| Investigations | ||||||
| Blood creatinine increased | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/13 (0%) | 2/15 (13.3%) | 0/20 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Neck pain | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Groin pain | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Cholangiocarcinoma | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Gallbladder cancer | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Metastases to central nervous system | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Pancreatic carcinoma | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Small cell lung cancer | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Nervous system disorders | ||||||
| Cerebrovascular accident | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Psychiatric disorders | ||||||
| Mental status changes | 0/13 (0%) | 0/15 (0%) | 2/20 (10%) | |||
| Confusional state | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Renal and urinary disorders | ||||||
| Renal failure acute | 0/13 (0%) | 1/15 (6.7%) | 6/20 (30%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 1/13 (7.7%) | 0/15 (0%) | 1/20 (5%) | |||
| Pulmonary embolism | 0/13 (0%) | 2/15 (13.3%) | 0/20 (0%) | |||
| Vascular disorders | ||||||
| Superior vena cava syndrome | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Hypotension | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/13 (92.3%) | 14/15 (93.3%) | 17/20 (85%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 2/13 (15.4%) | 3/15 (20%) | 3/20 (15%) | |||
| Leukocytosis | 1/13 (7.7%) | 1/15 (6.7%) | 2/20 (10%) | |||
| Thrombocytopenia | 0/13 (0%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Anaemia of chronic disease | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Iron deficiency anaemia | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Leukopenia | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Cardiac disorders | ||||||
| Cardiac failure congestive | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Cardiomegaly | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Sinus tachycardia | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Tinnitus | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Endocrine disorders | ||||||
| Hypothyroidism | 0/13 (0%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Eye disorders | ||||||
| Photopsia | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 4/13 (30.8%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Constipation | 1/13 (7.7%) | 1/15 (6.7%) | 2/20 (10%) | |||
| Abdominal distension | 0/13 (0%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Dry mouth | 0/13 (0%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Dyspepsia | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Dysphagia | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Flatulence | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Haematochezia | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Hiatus hernia | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Retching | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Stomatitis | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| General disorders | ||||||
| Malaise | 2/13 (15.4%) | 0/15 (0%) | 1/20 (5%) | |||
| Chills | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Early satiety | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Gait disturbance | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Hepatobiliary disorders | ||||||
| Bile duct stenosis | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Immune system disorders | ||||||
| Allergy to arthropod bite | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Infections and infestations | ||||||
| Urinary tract infection | 3/13 (23.1%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Oral candidiasis | 1/13 (7.7%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Bacteraemia | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Cellulitis | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Oropharyngeal candidiasis | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Periodontitis | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Respiratory tract infection | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Wound infection | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Injury, poisoning and procedural complications | ||||||
| Laceration | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 0/13 (0%) | 0/15 (0%) | 3/20 (15%) | |||
| Ammonia increased | 1/13 (7.7%) | 0/15 (0%) | 1/20 (5%) | |||
| Aspartate aminotransferase increased | 0/13 (0%) | 0/15 (0%) | 2/20 (10%) | |||
| Amylase increased | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Blood alkaline phosphatase increased | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Blood urea increased | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Lipase increased | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Waist circumference increased | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Weight increased | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 7/13 (53.8%) | 2/15 (13.3%) | 1/20 (5%) | |||
| Hyperkalaemia | 1/13 (7.7%) | 2/15 (13.3%) | 3/20 (15%) | |||
| Hyponatraemia | 2/13 (15.4%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Hypercalcaemia | 0/13 (0%) | 1/15 (6.7%) | 2/20 (10%) | |||
| Hypokalaemia | 1/13 (7.7%) | 0/15 (0%) | 2/20 (10%) | |||
| Hypomagnesaemia | 2/13 (15.4%) | 0/15 (0%) | 1/20 (5%) | |||
| Hypophosphataemia | 1/13 (7.7%) | 0/15 (0%) | 1/20 (5%) | |||
| Hyperglycaemia | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Hyperphosphataemia | 1/13 (7.7%) | 0/15 (0%) | 1/20 (5%) | |||
| Hyperuricaemia | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Iron deficiency | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Metabolic acidosis | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 2/13 (15.4%) | 0/15 (0%) | 3/20 (15%) | |||
| Pain in extremity | 1/13 (7.7%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Flank pain | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Muscular weakness | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Musculoskeletal chest pain | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Myalgia | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Nervous system disorders | ||||||
| Dizziness | 2/13 (15.4%) | 0/15 (0%) | 1/20 (5%) | |||
| Headache | 0/13 (0%) | 0/15 (0%) | 2/20 (10%) | |||
| Hepatic encephalopathy | 0/13 (0%) | 0/15 (0%) | 2/20 (10%) | |||
| Hypoaesthesia | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Neuropathy peripheral | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Paraesthesia | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Peroneal nerve palsy | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 3/13 (23.1%) | 2/15 (13.3%) | 1/20 (5%) | |||
| Anxiety | 0/13 (0%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Delirium | 0/13 (0%) | 0/15 (0%) | 2/20 (10%) | |||
| Depression | 0/13 (0%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Renal and urinary disorders | ||||||
| Renal failure | 0/13 (0%) | 1/15 (6.7%) | 1/20 (5%) | |||
| Urinary tract obstruction | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Scrotal oedema | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 1/13 (7.7%) | 2/15 (13.3%) | 3/20 (15%) | |||
| Pleural effusion | 1/13 (7.7%) | 2/15 (13.3%) | 1/20 (5%) | |||
| Haemoptysis | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Hypoxia | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Nasal congestion | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Productive cough | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Wheezing | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash macular | 1/13 (7.7%) | 0/15 (0%) | 1/20 (5%) | |||
| Rash pruritic | 2/13 (15.4%) | 0/15 (0%) | 0/20 (0%) | |||
| Night sweats | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Pruritus generalised | 0/13 (0%) | 1/15 (6.7%) | 0/20 (0%) | |||
| Rash maculo-papular | 0/13 (0%) | 0/15 (0%) | 1/20 (5%) | |||
| Vascular disorders | ||||||
| Deep vein thrombosis | 1/13 (7.7%) | 0/15 (0%) | 0/20 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Takeda |
| Phone | +1-866-835-2233 |
| GlobalOncologyMedinfo@takeda.com |
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01912222
Other Study ID Numbers:
- C16018
- U1111-1177-7929
First Posted:
Jul 31, 2013
Last Update Posted:
Jun 2, 2016
Last Verified:
Feb 1, 2016