Lupus Nephritis
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to characterize the safety and tolerability of ixazomib when administered as multiple oral doses at escalating dose levels in participants with lupus nephritis.
Detailed description
The drug being tested in this study is called ixazomib. Ixazomib is being tested to find a safe and well tolerated dose in participants with lupus nephritis. This study will look at side effects and lab results in participants who take ixazomib, along with the characterization of its pharmacokinetics (PK). This study is designed as a randomized, sequential-panel, multiple rising dose study. The study will enroll approximately 40 participants. The study population will consist of 4 Cohorts. At least 5 participants (4:1 active:placebo) will be recruited into the 0.5 mg dose group (Cohort A), at least 5 participants (4:1 active:placebo) in the 2.0 mg dose group (Cohort B), 8 participants (6:2 active:placebo) in the 3.0 mg dose group (Cohort C), and 8 participants (6:2 active:placebo) in the 4.0 mg dose group (Cohort D). Participants in each Cohort will be asked to take one capsule on Days 1, 8 and 15 in 28-day cycle, for 3 cycles. PK samples will be collected to measure concentrations of ixazomib. The starting dose in Cohort A will be 0.5 mg followed by administrations of 2, 3 and 4 mg in subsequent cohorts. This multi-center trial will be conducted in the United States and Europe. The overall time to participate in this study is up to 196 days. Participants will make 19 visits to the clinic during the treatment period and will make follow-up visits monthly for 3 months for follow-up assessments.
Interventions
DRUGIxazomib
Ixazomib capsules.
DRUGPlacebo
Ixazomib placebo-matching capsules.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. In the opinion of the investigator, is capable of understanding and complying with protocol requirements. 2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Is female or male and aged 18 to 75 years, inclusive. 4. Has a diagnosis of systemic lupus erythematosus (SLE) defined by meeting either the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria or the American College of Rheumatology (ACR) criteria for the classification of SLE. The 4 criteria required by ACR classification are not required to be present at Screening for eligibility. 5. Has a definite diagnosis of LN based on a kidney biopsy done within 2 year of the Screening Visit which demonstrated International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV or V changes \[excluding Class III (C), IV-S (C) and IV-G (C)\] or World Health Organization (WHO) 1982 classification Class III,IV or V(excluding Class IIIc and IVd). 1. If no biopsy was done within 2 year of Screening Visit, biopsy can be done during the screening period as a study procedure. 2. Co-existence of classes is permitted. 6. Has a renal biopsy demonstrating either ISN/RPS or WHO class V or class V with class 2 nephritis with a UPCR of greater than (\>) 3 or the participant has a renal biopsy demonstrating either active ISN/RPS or WHO class III or IV nephritis, defined by either one of the following criteria: a) A UPCR\* of \>=1.0 at Screening OR b) A UPCR\* \>0.5 at Screening and at least one of the following: i. Active urine sediment in the absence of infection or other cause within 3 months of screening, defined as at least one of the following: * \>=5 red blood cells (RBC) per high power field, not due to causes other than lupus nephritis. * \>=5 white blood cells (WBC) per high power field in the absence of infection. * Presence of cellular casts. ii. The participant has increased levels (above upper limit of normal \[ULN\]) serum dsDNA autoantibodies at screening. iii. Low complement (either C3 or C4) at Screening (\>= 25 percent \[%\] lower than lower limit of normal \[LLN\]). iv. Biopsy within 3 months prior to screening visit indicating active proliferative lupus glomerulonephritis ISN/RPS class III or IV changes \[excluding Class III (C), IV-S (C) and IV-G (C)\] or WHO 1982 classification Class III or IV (excluding Class IIIc and IVd), with co-existing Class V permitted. * Participants may be re-screened once for urinary sediment, proteinuria or complement levels within 2 weeks of the original screening visit. * UPCR value for eligibility will be based on the average UPCR obtained from the 3 specimens collected during screening. 7. Has had an inadequate response, in the judgment of the Investigator, to at least 6 months of an immunosuppressive regimen including single or sequential use of at least one of the following: cyclophosphamide (CYC), mycophenolate mofetil (MMF), mycophenolic acid (MA), or azathioprine (AZA). 8. If the participant is on glucocorticosteroids, must be on stable dose equivalent to 20 mg/day or less of prednisone for at least 2 weeks prior to first dose of study medication. Participant who are on a stable dose equivalent to \>20 mg/day and \<=30 milligram per day (mg/day) of prednisone may be allowed to the study if reviewed by the adjudication committee and approved by the medical monitor; however, the steroid dose should be tapered. 9. Male participants who are sexually active with women of child bearing potential (WOCBP), even if surgically sterilized (that is, status post-vasectomy), must: a) Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug. 10. Female participants who are of child bearing potential must: a) Agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug. 11. This study permits the re-enrollment of a participant that has discontinued the study as a pre- treatment failure (ie, participant has not been randomized). If re-enrolled, the participant must be re-consented. \* The re-enrollment of all participants who completed Cohort A and B is permitted to subsequent cohorts (2.0 mg and 3.0 mg dose cohorts) after completion of all cycles including the follow-up period if they had no drug-related adverse events greater than Grade 1, no adverse events greater than Grade 2, continue to meet all inclusion and
Exclusion criteria
, and the Safety Review Committee has reviewed and approved enrollment of the subject into a higher dose cohort. 12. Must be receiving Standard of Care (SOC) treatment with an immunosuppressant drug for the treatment of LN (example, MMF, MA or AZA).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants Who Experienced at Least One Grade Greater Than or Equal to (>=) 2 Treatment Emergent Adverse Event (TEAE) | Baseline up to Day 101 (30 days after last dose of study drug) |
| Percentage of Participants Who Experienced at Least One Treatment Emergent Serious Adverse Event (SAE) | Baseline up to Day 101 (30 days after last dose of study drug) |
| Percentage of Participants Who Experienced at Least One AE Leading to Study Drug Discontinuation | Baseline up to Day 168 |
| Percentage of Participants With at Least One Markedly Abnormal Value (MAV) for Hematologic Parameters | Baseline up to Day 168 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Complement Protein C3 and C4 at Day 84 | Baseline and Day 84 |
| Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Day 84 | Baseline and Day 84 |
| Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length is equal to [=] 28 days) |
| Change From Baseline in Serum Creatinine (sCR) Level at Day 84 | Baseline and Day 84 |
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Day 84 | Baseline and Day 84 |
| Change From Baseline in Levels of Autoantibodies (Anti-double-stranded Deoxyribonucleic Acid [dsDNA]) at Day 84 | Baseline and Day 84 |
Countries
France, Germany, Italy, Russia, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 8 investigative sites in the United States, Spain and Russia from 09 June 2014 to 19 January 2018.
Pre-assignment details
Participants with a historical diagnosis of lupus nephritis (LN) were enrolled to receive ixazomib as multiple rising doses (MRD) of 0.5 milligram (mg) in Cohort A and 2.0 mg in Cohort B. This study was terminated early after the completion of Cohorts A and B due to lack of sufficient enrollment to complete the study.
Participants by arm
| Arm | Count |
|---|---|
| Pooled Placebo Ixazomib placebo-matching capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle from Cycle 1 to Cycle 3. | 3 |
| Cohort A: Ixazomib 0.5 mg Ixazomib 0.5 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle from Cycle 1 to Cycle 3. | 5 |
| Cohort B: Ixazomib 2 mg Ixazomib 2 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle from Cycle 1 to Cycle 3. | 4 |
| Total | 12 |
Baseline characteristics
| Characteristic | Pooled Placebo | Total | Cohort B: Ixazomib 2 mg | Cohort A: Ixazomib 0.5 mg |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 12 Participants | 4 Participants | 5 Participants |
| Alcohol Classification Current drinker | 2 Participants | 5 Participants | 2 Participants | 1 Participants |
| Alcohol Classification Never drank | 1 Participants | 7 Participants | 2 Participants | 4 Participants |
| Body Mass Index (BMI) | 30.92 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.441 | 31.36 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.399 | 31.64 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.66 | 31.40 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.971 |
| Consumption of Alcohol Drank less than or equal to (<=) 4 drinks per day | 2 Participants | 5 Participants | 2 Participants | 1 Participants |
| Consumption of Alcohol Not reported | 1 Participants | 7 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 9 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Female Reproductive Status Female of childbearing potential | 1 Participants | 5 Participants | 1 Participants | 3 Participants |
| Female Reproductive Status Not applicable (participant were male) | 2 Participants | 4 Participants | 2 Participants | 0 Participants |
| Female Reproductive Status Surgically sterile | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Height | 169.3 centimeter (cm) STANDARD_DEVIATION 0.58 | 169.1 centimeter (cm) STANDARD_DEVIATION 4.48 | 171.5 centimeter (cm) STANDARD_DEVIATION 6.56 | 167.0 centimeter (cm) STANDARD_DEVIATION 3.39 |
| Pharmacogenomics (PGx) Consent Obtained PGx was not obtained | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Pharmacogenomics (PGx) Consent Obtained PGx was obtained | 3 Participants | 11 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 6 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Russia | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Spain | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 3 Participants | 10 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Female | 1 Participants | 8 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants | 0 Participants |
| Smoking Classification Current smoker | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Smoking Classification Ex-smoker | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Smoking Classification Never smoked | 2 Participants | 9 Participants | 2 Participants | 5 Participants |
| Weight | 88.67 kilogram (kg) STANDARD_DEVIATION 4.216 | 89.46 kilogram (kg) STANDARD_DEVIATION 11.229 | 92.43 kilogram (kg) STANDARD_DEVIATION 7.192 | 87.56 kilogram (kg) STANDARD_DEVIATION 16.891 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 3 / 3 | 5 / 5 | 3 / 4 |
| serious Total, serious adverse events | 0 / 3 | 0 / 5 | 1 / 4 |
Outcome results
Primary
Percentage of Participants Who Experienced at Least One AE Leading to Study Drug Discontinuation
Time frame: Baseline up to Day 168
Population: The safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pooled Placebo | Percentage of Participants Who Experienced at Least One AE Leading to Study Drug Discontinuation | 0 percentage of participants |
| Cohort A: Ixazomib 0.5 mg | Percentage of Participants Who Experienced at Least One AE Leading to Study Drug Discontinuation | 0 percentage of participants |
| Cohort B: Ixazomib 2 mg | Percentage of Participants Who Experienced at Least One AE Leading to Study Drug Discontinuation | 0 percentage of participants |
Primary
Percentage of Participants Who Experienced at Least One Grade Greater Than or Equal to (>=) 2 Treatment Emergent Adverse Event (TEAE)
Time frame: Baseline up to Day 101 (30 days after last dose of study drug)
Population: The safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pooled Placebo | Percentage of Participants Who Experienced at Least One Grade Greater Than or Equal to (>=) 2 Treatment Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| Cohort A: Ixazomib 0.5 mg | Percentage of Participants Who Experienced at Least One Grade Greater Than or Equal to (>=) 2 Treatment Emergent Adverse Event (TEAE) | 20.0 percentage of participants |
| Cohort B: Ixazomib 2 mg | Percentage of Participants Who Experienced at Least One Grade Greater Than or Equal to (>=) 2 Treatment Emergent Adverse Event (TEAE) | 25.0 percentage of participants |
Primary
Percentage of Participants Who Experienced at Least One Treatment Emergent Serious Adverse Event (SAE)
Time frame: Baseline up to Day 101 (30 days after last dose of study drug)
Population: The safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pooled Placebo | Percentage of Participants Who Experienced at Least One Treatment Emergent Serious Adverse Event (SAE) | 0 percentage of participants |
| Cohort A: Ixazomib 0.5 mg | Percentage of Participants Who Experienced at Least One Treatment Emergent Serious Adverse Event (SAE) | 0 percentage of participants |
| Cohort B: Ixazomib 2 mg | Percentage of Participants Who Experienced at Least One Treatment Emergent Serious Adverse Event (SAE) | 0 percentage of participants |
Primary
Percentage of Participants With at Least One Markedly Abnormal Value (MAV) for Hematologic Parameters
Time frame: Baseline up to Day 168
Population: The safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pooled Placebo | Percentage of Participants With at Least One Markedly Abnormal Value (MAV) for Hematologic Parameters | 0 percentage of participants |
| Cohort A: Ixazomib 0.5 mg | Percentage of Participants With at Least One Markedly Abnormal Value (MAV) for Hematologic Parameters | 0 percentage of participants |
| Cohort B: Ixazomib 2 mg | Percentage of Participants With at Least One Markedly Abnormal Value (MAV) for Hematologic Parameters | 50.0 percentage of participants |
Secondary
Change From Baseline in Complement Protein C3 and C4 at Day 84
Time frame: Baseline and Day 84
Population: The PD set consisted of all participants who received study drug and had at least 1 post dose PD measurement. Participants who were evaluable for this measure at given time period for the arm were included in the category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Change From Baseline in Complement Protein C3 and C4 at Day 84 | Complement Protein C3: Baseline | 122.3 milligram per deciliter (mg/dL) | Standard Deviation 59.47 |
| Pooled Placebo | Change From Baseline in Complement Protein C3 and C4 at Day 84 | Complement Protein C3: Change at Day 84 | -20.3 milligram per deciliter (mg/dL) | Standard Deviation 26.76 |
| Pooled Placebo | Change From Baseline in Complement Protein C3 and C4 at Day 84 | Complement Protein C4: Baseline | 29.0 milligram per deciliter (mg/dL) | Standard Deviation 13.08 |
| Pooled Placebo | Change From Baseline in Complement Protein C3 and C4 at Day 84 | Complement Protein C4: Change at Day 84 | -4.7 milligram per deciliter (mg/dL) | Standard Deviation 4.73 |
| Cohort A: Ixazomib 0.5 mg | Change From Baseline in Complement Protein C3 and C4 at Day 84 | Complement Protein C4: Change at Day 84 | -0.8 milligram per deciliter (mg/dL) | Standard Deviation 1.92 |
| Cohort A: Ixazomib 0.5 mg | Change From Baseline in Complement Protein C3 and C4 at Day 84 | Complement Protein C3: Baseline | 82.2 milligram per deciliter (mg/dL) | Standard Deviation 23.67 |
| Cohort A: Ixazomib 0.5 mg | Change From Baseline in Complement Protein C3 and C4 at Day 84 | Complement Protein C4: Baseline | 12.4 milligram per deciliter (mg/dL) | Standard Deviation 8.26 |
| Cohort A: Ixazomib 0.5 mg | Change From Baseline in Complement Protein C3 and C4 at Day 84 | Complement Protein C3: Change at Day 84 | -7.4 milligram per deciliter (mg/dL) | Standard Deviation 10.5 |
| Cohort B: Ixazomib 2 mg | Change From Baseline in Complement Protein C3 and C4 at Day 84 | Complement Protein C4: Change at Day 84 | -6.0 milligram per deciliter (mg/dL) | Standard Deviation 1.41 |
| Cohort B: Ixazomib 2 mg | Change From Baseline in Complement Protein C3 and C4 at Day 84 | Complement Protein C3: Change at Day 84 | -19.5 milligram per deciliter (mg/dL) | Standard Deviation 13.18 |
| Cohort B: Ixazomib 2 mg | Change From Baseline in Complement Protein C3 and C4 at Day 84 | Complement Protein C4: Baseline | 20.0 milligram per deciliter (mg/dL) | Standard Deviation 9.56 |
| Cohort B: Ixazomib 2 mg | Change From Baseline in Complement Protein C3 and C4 at Day 84 | Complement Protein C3: Baseline | 110.3 milligram per deciliter (mg/dL) | Standard Deviation 40.24 |
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Day 84
Time frame: Baseline and Day 84
Population: The safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Day 84 | Baseline | 88.7 milliliter/minute/1.73 square meter | Standard Deviation 28.11 |
| Pooled Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Day 84 | Change at Day 84 | 6.3 milliliter/minute/1.73 square meter | Standard Deviation 22.19 |
| Cohort A: Ixazomib 0.5 mg | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Day 84 | Baseline | 130.0 milliliter/minute/1.73 square meter | Standard Deviation 62.02 |
| Cohort A: Ixazomib 0.5 mg | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Day 84 | Change at Day 84 | 2.6 milliliter/minute/1.73 square meter | Standard Deviation 29.26 |
| Cohort B: Ixazomib 2 mg | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Day 84 | Baseline | 103.5 milliliter/minute/1.73 square meter | Standard Deviation 38.77 |
| Cohort B: Ixazomib 2 mg | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Day 84 | Change at Day 84 | -0.5 milliliter/minute/1.73 square meter | Standard Deviation 19.6 |
Secondary
Change From Baseline in Levels of Autoantibodies (Anti-double-stranded Deoxyribonucleic Acid [dsDNA]) at Day 84
Time frame: Baseline and Day 84
Population: The pharmacodynamics (PD) set consisted of all participants who received study drug and had at least 1 post dose PD measurement. Participants who were evaluable for this measure at given time period for the arm were included in the category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Change From Baseline in Levels of Autoantibodies (Anti-double-stranded Deoxyribonucleic Acid [dsDNA]) at Day 84 | Baseline | 18.7 international units/milliliter (IU/mL) | Standard Deviation 12.7 |
| Pooled Placebo | Change From Baseline in Levels of Autoantibodies (Anti-double-stranded Deoxyribonucleic Acid [dsDNA]) at Day 84 | Change at Day 84 | -4.3 international units/milliliter (IU/mL) | Standard Deviation 6.03 |
| Cohort A: Ixazomib 0.5 mg | Change From Baseline in Levels of Autoantibodies (Anti-double-stranded Deoxyribonucleic Acid [dsDNA]) at Day 84 | Baseline | 34.3 international units/milliliter (IU/mL) | Standard Deviation 32.57 |
| Cohort A: Ixazomib 0.5 mg | Change From Baseline in Levels of Autoantibodies (Anti-double-stranded Deoxyribonucleic Acid [dsDNA]) at Day 84 | Change at Day 84 | 7.5 international units/milliliter (IU/mL) | Standard Deviation 9.4 |
| Cohort B: Ixazomib 2 mg | Change From Baseline in Levels of Autoantibodies (Anti-double-stranded Deoxyribonucleic Acid [dsDNA]) at Day 84 | Baseline | 129.3 international units/milliliter (IU/mL) | Standard Deviation 140.66 |
| Cohort B: Ixazomib 2 mg | Change From Baseline in Levels of Autoantibodies (Anti-double-stranded Deoxyribonucleic Acid [dsDNA]) at Day 84 | Change at Day 84 | 9.5 international units/milliliter (IU/mL) | Standard Deviation 75.76 |
Secondary
Change From Baseline in Serum Creatinine (sCR) Level at Day 84
Time frame: Baseline and Day 84
Population: The safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Change From Baseline in Serum Creatinine (sCR) Level at Day 84 | Baseline | 91.347 micromoles per liter (mcmol/L) | Standard Deviation 18.4019 |
| Pooled Placebo | Change From Baseline in Serum Creatinine (sCR) Level at Day 84 | Change at Day 84 | -2.947 micromoles per liter (mcmol/L) | Standard Deviation 22.2468 |
| Cohort A: Ixazomib 0.5 mg | Change From Baseline in Serum Creatinine (sCR) Level at Day 84 | Baseline | 72.488 micromoles per liter (mcmol/L) | Standard Deviation 54.2779 |
| Cohort A: Ixazomib 0.5 mg | Change From Baseline in Serum Creatinine (sCR) Level at Day 84 | Change at Day 84 | 1.768 micromoles per liter (mcmol/L) | Standard Deviation 7.3961 |
| Cohort B: Ixazomib 2 mg | Change From Baseline in Serum Creatinine (sCR) Level at Day 84 | Baseline | 81.770 micromoles per liter (mcmol/L) | Standard Deviation 31.7708 |
| Cohort B: Ixazomib 2 mg | Change From Baseline in Serum Creatinine (sCR) Level at Day 84 | Change at Day 84 | 13.260 micromoles per liter (mcmol/L) | Standard Deviation 39.2029 |
Secondary
Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Day 84
Time frame: Baseline and Day 84
Population: The safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Day 84 | Baseline | 1.7567 milligram per milligram creatinine | Standard Deviation 1.66796 |
| Pooled Placebo | Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Day 84 | Change at Day 84 | -0.1680 milligram per milligram creatinine | Standard Deviation 1.03388 |
| Cohort A: Ixazomib 0.5 mg | Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Day 84 | Baseline | 2.6134 milligram per milligram creatinine | Standard Deviation 2.111 |
| Cohort A: Ixazomib 0.5 mg | Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Day 84 | Change at Day 84 | -0.4740 milligram per milligram creatinine | Standard Deviation 0.96565 |
| Cohort B: Ixazomib 2 mg | Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Day 84 | Baseline | 0.7535 milligram per milligram creatinine | Standard Deviation 0.40827 |
| Cohort B: Ixazomib 2 mg | Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Day 84 | Change at Day 84 | 0.9943 milligram per milligram creatinine | Standard Deviation 0.73183 |
Secondary
Plasma Concentrations of Ixazomib at Each Scheduled Collection Time
Time frame: Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length is equal to [=] 28 days)
Population: The pharmacokinetic (PK) set consisted of all participants who received one dose of ixazomib and had at least 1 measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | Pre-dose | 0.0000 nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| Pooled Placebo | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 0.25 hour | 0.0000 nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| Pooled Placebo | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 0.5 hour | 0.4244 nanogram per milliliter (ng/mL) | Standard Deviation 0.69887 |
| Pooled Placebo | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 1 hour | 0.6776 nanogram per milliliter (ng/mL) | Standard Deviation 0.68219 |
| Pooled Placebo | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 1.5 hours | 0.5056 nanogram per milliliter (ng/mL) | Standard Deviation 0.72535 |
| Pooled Placebo | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 2 hours | 0.5134 nanogram per milliliter (ng/mL) | Standard Deviation 0.52152 |
| Pooled Placebo | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 4 hours | 0.1082 nanogram per milliliter (ng/mL) | Standard Deviation 0.24194 |
| Pooled Placebo | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 8 hours | 0.0000 nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| Pooled Placebo | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 24 hours | 0.0000 nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| Pooled Placebo | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 168 hours | 0.0000 nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| Cohort A: Ixazomib 0.5 mg | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 8 hours | 0.9967 nanogram per milliliter (ng/mL) | Standard Deviation 0.86327 |
| Cohort A: Ixazomib 0.5 mg | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | Pre-dose | 0.0000 nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| Cohort A: Ixazomib 0.5 mg | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 2 hours | 2.2767 nanogram per milliliter (ng/mL) | Standard Deviation 2.07447 |
| Cohort A: Ixazomib 0.5 mg | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 0.25 hour | 0.0000 nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| Cohort A: Ixazomib 0.5 mg | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 168 hours | 0.0000 nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| Cohort A: Ixazomib 0.5 mg | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 0.5 hour | 2.5033 nanogram per milliliter (ng/mL) | Standard Deviation 4.3359 |
| Cohort A: Ixazomib 0.5 mg | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 4 hours | 1.1700 nanogram per milliliter (ng/mL) | Standard Deviation 1.01602 |
| Cohort A: Ixazomib 0.5 mg | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 1 hour | 2.2000 nanogram per milliliter (ng/mL) | Standard Deviation 2.35841 |
| Cohort A: Ixazomib 0.5 mg | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 24 hours | 0.5493 nanogram per milliliter (ng/mL) | Standard Deviation 0.48634 |
| Cohort A: Ixazomib 0.5 mg | Plasma Concentrations of Ixazomib at Each Scheduled Collection Time | 1.5 hours | 2.3400 nanogram per milliliter (ng/mL) | Standard Deviation 2.38627 |