Multiple Myeloma
Conditions
Brief summary
The purpose of the study is to assess the concentration of Elotuzumab in Myeloma patients with very low kidney function including patients on dialysis.
Interventions
DRUGLenalidomide
Capsules, Oral, 15 mg, One capsule every 48 hours through Days 1-21 (Repeat every 28 days until subject meets criteria for discontinuation of study drug
DRUGDexamethasone
Tablets, Oral, 28 mg weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond) Repeat every 28 days until subject meets criteria for discontinuation of study drug
BIOLOGICALElotuzumab (BMS-901608; HuLuc63)
Solution, Intravenous, 10 mg/kg, weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug
Sponsors
AbbVie
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with Multiple Myeloma (MM) and renal function fitting one of three categories: 1. Severe renal impairment: estimated creatinine clearance (CrCl) \<30 ml/min, but not requiring dialysis 2. End-stage renal disease: requiring hemodialysis 3. Normal renal function: estimated CrCl ≥90 ml/min * Documented evidence of symptomatic MM, either newly diagnosed or relapsed/refractory * Prior Lenalidomide exposure is permitted only if the subject did not discontinue Lenalidomide due to a Grade ≥3 related Adverse Event (AE)
Exclusion criteria
* Monoclonal Gammopathy of Undetermined Significance (MGUS), Waldenstrom's macroglobulinemia, or smoldering myeloma * Active plasma cell leukemia * All adverse events of any prior chemotherapy, surgery, or radiotherapy not resolved * POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) * Acute renal failure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | Day 1 of Cycle 1 to 28 days post dose | The quantification of elotuzumab in human serum was performed using a validated Enzyme-linked immunoassay (ELISA). Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Cmax was measured in micrograms per milliliter (µg/mL). Pharmacokinetic (PK) parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group. |
| Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method | Day 1 of Cycle 1 to 28 days post dose | The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD participants had 2 additional sample times: immediately prior to and immediately after dialysis. AUC was measured in µg\*h/mL. PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | From first dose (Day 1) to last dose plus 60 days, up to Primary Endpoint (June 2014), approximately 2 years | Serum samples were evaluated for the presence of ADAs using a validated bridging electrochemiluminescence (ECL) immunoassay. Samples in: Cycle 1, Day 1 0 h (pre-dose), Cycle 2, Day 1(Study Day 29), 0 h (pre-dose; 672 h post-dose), Cycle 3, Day 1, 0 h and in cycle thereafter, at end of study/discontinuation, and at 30 and 60 day follow up visits post treatment. ADA Positive Participant: baseline negative with at least one ADA positive sample at any time after initiation of treatment or baseline positive with at least one ADA positive sample at any time after initiation of treatment with a titer 9-fold greater than the baseline; Persistent Positive: ADA positive at 2 or more sequential timepoints at least 12 weeks apart; Last Sample Positive: Not persistent positive and ADA Positive Sample in the last sampling timepoint; Other Positive: not persistent positive with ADA negative sample in the last sampling; ADA Negative: no ADA positive sample after the initiation of treatment. |
| Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months) | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. |
| Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months) | National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Hemoglobin Gr 1:\<LLN to 10.0 g/dL, Gr 2:\<10.0 to 8.0 g/dL, Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL. Lymphocytes absolute (abs) Gr 1: \<1.5 to 0.8 \*10\^3 c/µL, Gr 2 \<0.8 to 0.5 \*10\^3 c/µL, Gr 3: \<0.5 to 0.2 \*10\^3 c/µL, Gr 4: \<0.2\*10\^3 c/µL. Neutrophils abs: Gr 1:\<LLN to 1.5\*10\^9/L, Gr 2:\<1.5 to 1.0\*10\^9/L, Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L. Platelet count Gr 1:LLN to 75.0\*10\^9/L, Gr 2:\<75.0 to 50.0\*10\^9/L, Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L. Leukocytes Gr 1:\<LLN to 3.0 \*10\^3 c/µL, Gr 2; \<3.0 to 2.0 \*10\^3 c/µL, Gr 3: \<2.0 to 1.0 \*10\^3 c/µL, Gr 4: \<1.0 \*10\^3 c/µL. |
| Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months) | NCI CTCAE, version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Upper Limits of Normal (ULN). Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP). ALT Grade (Gr)1:\>1.0 to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. AST Gr 1: \>1.0 to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. Total bilirubin Gr 1: \>1.0 to 1.5\*ULN; Gr 2: \>1.5 to 3.0\*ULN; Gr 3: \>3.0 to 10..0\*ULN; Gr 4: \>10.0.0\*ULN. ALP (U/L) Gr1:\>1.0 to 2.5\*ULN, Gr2:\>2.5 to 5.0\*ULN, Gr3:\>5.0 to 20.0\*ULN, Gr4:\>20.0\*ULN. Albumin (low) Gr 1:\<LLN to 3 grams per deciliter (g/dL); Gr 2: \<3.0 - 2.0 g/L; Gr 3: \< 2 g/dL. Creatinine Gr 1: \>1 - 1.5\*baseline (BL)to \>ULN - 1.5\*ULN; Gr 2: \>1.5 - 3.0\*BL to \> 1.5 - 3.0\*ULN; Gr 3: \>3.0\*BL to \> 3.0 - 6.0\*ULN; Gr 4: \>6.0\*ULN. |
| Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months) | Sodium high (H) Gr 1:\>ULN - 150; Gr 2: \>150 - 155; Gr 3: \>155 - 160; Gr 4: \>160 mmol/L; Sodium low(L) Gr 1:\<LLN - 130; Gr 3: \<130 - 120; Gr 4: \<120 mmol/L. Potassium (H) Gr 1: \>ULN - 5.5; Gr 2: \>5.5 - 6.0; Gr 3: \> 6.0 - 7.0; Gr 4: \>7.0 mmol/L; Potassium (L) Gr 1: \<LLN - 3.0; Gr 2: \<LLN - 3.0; Gr 3: \< 3.0 - 2.5; Gr 4: \<2.5 mmol/L. Bicarbonate Gr1: 16-\<LLN, Gr2: 11-16, Gr3, 8-11, Gr4: \<8 milliequivalents per liter (mEq/L). Phosphorus Gr 1: 2.5 - \<LLN, Gr2 2.0-\<2.5, Gr3: 1.0-\<2.0, Gr4: \<1.0. Calcium (L) Gr 1: \<LLN to 8.0; Gr2: 7.0 - 8.0; Gr3: 6.0-7.0; Gr 4: \<6.0 mg/dL; calcium (H) Gr1:\>ULN - 11.5, Gr2:\>11.5 - 12.5, Gr3: 12.5 - 13.5, Gr4: \>13.5. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Apparent Volume of Distribution (Vz) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | Day 1 of Cycle 1 to 28 days post dose | The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Vz was measured in mL per kilogram body weight (mL/kg). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group. |
| Geometric Mean Total Body Clearance (CLT) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | Day 1 of Cycle 1 to 28 days post dose | The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. CLT was measured in mL per hour per kilogram body weight (mL/h/kg). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group. |
| Mean Terminal-phase Elimination Half-life (T-Half) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | Day 1 of Cycle 1 to 28 days post dose | The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. T-Half was measured in hours (h). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group. |
| Median Time to Maximal Concentration (Tmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | Day 1 of Cycle 1 to 28 days post dose | The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Tmax was measured in hours (h). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group. |
Countries
United States
Participant flow
Pre-assignment details
35 participants were enrolled; 9 did not enter into the treatment period. Reasons for not entering treatment period: 8 no longer met criteria, 1 other.
Participants by arm
| Arm | Count |
|---|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min). | 8 |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl \< 30 ml/min but no dialysis. | 9 |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis. | 9 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse event unrelated to study drug | 0 | 3 | 0 |
| Overall Study | Disease Progression | 4 | 3 | 5 |
| Overall Study | Investigator removed subject from study | 0 | 1 | 0 |
| Overall Study | Study drug toxicity | 1 | 0 | 0 |
| Overall Study | Subject converted to roll-over study | 0 | 1 | 0 |
| Overall Study | Subject decided to move to transplant | 1 | 0 | 0 |
| Overall Study | Subject plateaued in terms of effect | 1 | 0 | 0 |
| Overall Study | Subject request stop study treatment | 0 | 1 | 0 |
| Overall Study | Subject switched to commercial supply | 1 | 0 | 2 |
| Overall Study | Subject to receive non-protocol therapy | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Elotuzumab + LD in Normal Renal Function (NRF) Participants | Total |
|---|---|---|---|---|
| Age, Continuous | 75.9 years STANDARD_DEVIATION 7.7 | 55.6 years STANDARD_DEVIATION 11.7 | 57.8 years STANDARD_DEVIATION 8.05 | 63.3 years STANDARD_DEVIATION 13.02 |
| Age, Customized >=65 and < 75 years | 3 participants | 0 participants | 1 participants | 4 participants |
| Age, Customized < 65 years | 1 participants | 8 participants | 7 participants | 16 participants |
| Age, Customized >= 75 years | 5 participants | 1 participants | 0 participants | 6 participants |
| Region of Enrollment United States | 9 participants | 9 participants | 8 participants | 26 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 5 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 9 / 9 | 9 / 9 |
| serious Total, serious adverse events | 3 / 8 | 5 / 9 | 7 / 9 |
Outcome results
Primary
Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method
The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD participants had 2 additional sample times: immediately prior to and immediately after dialysis. AUC was measured in µg\*h/mL. PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group
Time frame: Day 1 of Cycle 1 to 28 days post dose
Population: The analyses of primary endpoint of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method | AUC (0-T) | 39559 µg*h/mL | Geometric Coefficient of Variation 28 |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method | AUC (INF) | 46401 µg*h/mL | Geometric Coefficient of Variation 39 |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method | AUC (0-T) | 50080 µg*h/mL | Geometric Coefficient of Variation 20 |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method | AUC (INF) | 60255 µg*h/mL | Geometric Coefficient of Variation 31 |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method | AUC (0-T) | 45937 µg*h/mL | Geometric Coefficient of Variation 31 |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method | AUC (INF) | 51227 µg*h/mL | Geometric Coefficient of Variation 39 |
Comparison: AUC(0-T). The reference arm is NRF participants.p-value: 0.16490% CI: [95.52, 167.783]ANOVA
Comparison: AUC(0-T). The reference arm is NRF participants.p-value: 0.35590% CI: [88.458, 152.439]ANOVA
Comparison: AUC (INF). The reference arm is NRF participants.p-value: 0.22890% CI: [90.366, 186.609]ANOVA
Comparison: AUC(INF). The reference arm is NRF participants.p-value: 0.64290% CI: [76.825, 158.647]ANOVA
Primary
Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
The quantification of elotuzumab in human serum was performed using a validated Enzyme-linked immunoassay (ELISA). Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Cmax was measured in micrograms per milliliter (µg/mL). Pharmacokinetic (PK) parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.
Time frame: Day 1 of Cycle 1 to 28 days post dose
Population: The analyses of primary endpoint of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 217 µg/mL | Geometric Coefficient of Variation 24 |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 226 µg/mL | Geometric Coefficient of Variation 10 |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 218 µg/mL | Geometric Coefficient of Variation 21 |
Comparison: The reference arm is NRF participants.p-value: 0.70490% CI: [86.983, 124.576]ANOVA
Comparison: The reference arm is NRF participants.p-value: 0.96590% CI: [84.453, 119.488]ANOVA
Secondary
Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose.
Serum samples were evaluated for the presence of ADAs using a validated bridging electrochemiluminescence (ECL) immunoassay. Samples in: Cycle 1, Day 1 0 h (pre-dose), Cycle 2, Day 1(Study Day 29), 0 h (pre-dose; 672 h post-dose), Cycle 3, Day 1, 0 h and in cycle thereafter, at end of study/discontinuation, and at 30 and 60 day follow up visits post treatment. ADA Positive Participant: baseline negative with at least one ADA positive sample at any time after initiation of treatment or baseline positive with at least one ADA positive sample at any time after initiation of treatment with a titer 9-fold greater than the baseline; Persistent Positive: ADA positive at 2 or more sequential timepoints at least 12 weeks apart; Last Sample Positive: Not persistent positive and ADA Positive Sample in the last sampling timepoint; Other Positive: not persistent positive with ADA negative sample in the last sampling; ADA Negative: no ADA positive sample after the initiation of treatment.
Time frame: From first dose (Day 1) to last dose plus 60 days, up to Primary Endpoint (June 2014), approximately 2 years
Population: All participants with baseline ADA result and at least one on-treatment ADA result.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | On-Study ADA Positive | 2 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Last Sample Positive | 1 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Persistent Positive | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Baseline ADA Positive | 1 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | On-Study ADA Negative | 4 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Other Positive | 1 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Positive at Cycle 2 pre-dose | 2 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Persistent Positive | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Baseline ADA Positive | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | On-Study ADA Positive | 1 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Positive at Cycle 2 pre-dose | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Last Sample Positive | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Other Positive | 1 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | On-Study ADA Negative | 3 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Last Sample Positive | 1 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | On-Study ADA Positive | 1 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | On-Study ADA Negative | 5 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Other Positive | 0 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Persistent Positive | 0 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Positive at Cycle 2 pre-dose | 1 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. | Baseline ADA Positive | 0 participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time frame: From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Population: All participants who received at least one dose of study treatment (at least one dose of any drug) were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | Deaths | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | AEs Leading to Discontinuation | 1 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | Any SAE | 3 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | Any SAE | 5 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | AEs Leading to Discontinuation | 4 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | Deaths | 0 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | Any SAE | 7 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | AEs Leading to Discontinuation | 1 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | Deaths | 0 participants |
Secondary
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests
Sodium high (H) Gr 1:\>ULN - 150; Gr 2: \>150 - 155; Gr 3: \>155 - 160; Gr 4: \>160 mmol/L; Sodium low(L) Gr 1:\<LLN - 130; Gr 3: \<130 - 120; Gr 4: \<120 mmol/L. Potassium (H) Gr 1: \>ULN - 5.5; Gr 2: \>5.5 - 6.0; Gr 3: \> 6.0 - 7.0; Gr 4: \>7.0 mmol/L; Potassium (L) Gr 1: \<LLN - 3.0; Gr 2: \<LLN - 3.0; Gr 3: \< 3.0 - 2.5; Gr 4: \<2.5 mmol/L. Bicarbonate Gr1: 16-\<LLN, Gr2: 11-16, Gr3, 8-11, Gr4: \<8 milliequivalents per liter (mEq/L). Phosphorus Gr 1: 2.5 - \<LLN, Gr2 2.0-\<2.5, Gr3: 1.0-\<2.0, Gr4: \<1.0. Calcium (L) Gr 1: \<LLN to 8.0; Gr2: 7.0 - 8.0; Gr3: 6.0-7.0; Gr 4: \<6.0 mg/dL; calcium (H) Gr1:\>ULN - 11.5, Gr2:\>11.5 - 12.5, Gr3: 12.5 - 13.5, Gr4: \>13.5.
Time frame: From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Population: All participants who received at least one dose of study treatment (at least one dose of any drug) were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium High Any Grade | 2 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium High Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium Low Any Grade | 2 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium Low Grade 3-4 | 1 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium High Any Grade | 2 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium High Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium Low Any Grade | 2 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium Low Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Bicarbonate Any Grade | 5 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Bicarbonate Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Calcium High Any Grade | 1 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Calcium High Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Calcium Low Any Grade | 4 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Calcium Low Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Glucose High Any Grade | 7 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Glucose High Grade 3-4 | 3 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Glucose Low Any Grade | 1 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Glucose Low Grade 3-4 | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Glucose Low Grade 3-4 | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium High Any Grade | 3 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Bicarbonate Grade 3-4 | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Calcium Low Any Grade | 6 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium High Grade 3-4 | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Glucose High Any Grade | 9 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Glucose High Grade 3-4 | 4 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium Low Any Grade | 6 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Calcium High Any Grade | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Glucose Low Any Grade | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium Low Grade 3-4 | 1 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Bicarbonate Any Grade | 8 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Calcium Low Grade 3-4 | 1 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium High Any Grade | 2 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium Low Grade 3-4 | 2 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Calcium High Grade 3-4 | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium High Grade 3-4 | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium Low Any Grade | 5 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium High Grade 3-4 | 3 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium Low Any Grade | 6 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium Low Grade 3-4 | 1 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Glucose High Any Grade | 7 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Bicarbonate Any Grade | 6 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Glucose Low Grade 3-4 | 0 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Bicarbonate Grade 3-4 | 0 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Calcium High Any Grade | 3 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Glucose High Grade 3-4 | 3 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Calcium High Grade 3-4 | 1 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium High Any Grade | 2 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium High Grade 3-4 | 0 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Calcium Low Any Grade | 8 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium Low Any Grade | 5 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium Low Grade 3-4 | 0 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium High Any Grade | 4 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Calcium Low Grade 3-4 | 2 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Glucose Low Any Grade | 1 participants |
Secondary
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Hemoglobin Gr 1:\<LLN to 10.0 g/dL, Gr 2:\<10.0 to 8.0 g/dL, Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL. Lymphocytes absolute (abs) Gr 1: \<1.5 to 0.8 \*10\^3 c/µL, Gr 2 \<0.8 to 0.5 \*10\^3 c/µL, Gr 3: \<0.5 to 0.2 \*10\^3 c/µL, Gr 4: \<0.2\*10\^3 c/µL. Neutrophils abs: Gr 1:\<LLN to 1.5\*10\^9/L, Gr 2:\<1.5 to 1.0\*10\^9/L, Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L. Platelet count Gr 1:LLN to 75.0\*10\^9/L, Gr 2:\<75.0 to 50.0\*10\^9/L, Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L. Leukocytes Gr 1:\<LLN to 3.0 \*10\^3 c/µL, Gr 2; \<3.0 to 2.0 \*10\^3 c/µL, Gr 3: \<2.0 to 1.0 \*10\^3 c/µL, Gr 4: \<1.0 \*10\^3 c/µL.
Time frame: From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Population: All participants who received at least one dose of study treatment (at least one dose of any drug) were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Hemoglobin Any Grade | 8 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Hemoglobin Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Platelet Count Any Grade | 7 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Platelet Count Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Leukocytes Any Grade | 8 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Lymphocytes (Abs) Any Grade | 8 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Lymphocytes (Abs) Grade 3-4 | 6 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Neutrophil Count (Abs) Any Grade | 6 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Neutrophil Count (Abs) Grade 3-4 | 3 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Leukocytes Grade 3-4 | 3 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Platelet Count Grade 3-4 | 2 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Neutrophil Count (Abs) Any Grade | 5 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Leukocytes Any Grade | 8 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Leukocytes Grade 3-4 | 1 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Lymphocytes (Abs) Any Grade | 9 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Hemoglobin Any Grade | 9 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Lymphocytes (Abs) Grade 3-4 | 9 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Hemoglobin Grade 3-4 | 2 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Platelet Count Any Grade | 8 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Neutrophil Count (Abs) Grade 3-4 | 1 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Neutrophil Count (Abs) Grade 3-4 | 2 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Platelet Count Grade 3-4 | 2 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Hemoglobin Grade 3-4 | 6 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Hemoglobin Any Grade | 9 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Leukocytes Any Grade | 6 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Lymphocytes (Abs) Grade 3-4 | 5 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Leukocytes Grade 3-4 | 2 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Neutrophil Count (Abs) Any Grade | 6 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Platelet Count Any Grade | 8 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Lymphocytes (Abs) Any Grade | 9 participants |
Secondary
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests
NCI CTCAE, version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Upper Limits of Normal (ULN). Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP). ALT Grade (Gr)1:\>1.0 to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. AST Gr 1: \>1.0 to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. Total bilirubin Gr 1: \>1.0 to 1.5\*ULN; Gr 2: \>1.5 to 3.0\*ULN; Gr 3: \>3.0 to 10..0\*ULN; Gr 4: \>10.0.0\*ULN. ALP (U/L) Gr1:\>1.0 to 2.5\*ULN, Gr2:\>2.5 to 5.0\*ULN, Gr3:\>5.0 to 20.0\*ULN, Gr4:\>20.0\*ULN. Albumin (low) Gr 1:\<LLN to 3 grams per deciliter (g/dL); Gr 2: \<3.0 - 2.0 g/L; Gr 3: \< 2 g/dL. Creatinine Gr 1: \>1 - 1.5\*baseline (BL)to \>ULN - 1.5\*ULN; Gr 2: \>1.5 - 3.0\*BL to \> 1.5 - 3.0\*ULN; Gr 3: \>3.0\*BL to \> 3.0 - 6.0\*ULN; Gr 4: \>6.0\*ULN.
Time frame: From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Population: All participants who received at least one dose of study treatment (at least one dose of any drug) were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALP Any Grade | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALP Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | AST Any Grade | 3 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | AST Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALT Any Grade | 2 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALT Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Bilirubin Any Grade | 1 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Bilirubin Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Creatinine Any Grade | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Creatinine Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Albumin Grade 3-4 | 0 participants |
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Albumin Any Grade | 2 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Bilirubin Any Grade | 1 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALP Any Grade | 3 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALT Any Grade | 5 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Creatinine Any Grade | 9 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALP Grade 3-4 | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Albumin Any Grade | 7 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Bilirubin Grade 3-4 | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | AST Any Grade | 2 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALT Grade 3-4 | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Albumin Grade 3-4 | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | AST Grade 3-4 | 0 participants |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Creatinine Grade 3-4 | 2 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | AST Grade 3-4 | 0 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALT Any Grade | 5 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Albumin Grade 3-4 | 0 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALT Grade 3-4 | 0 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Creatinine Grade 3-4 | 9 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Bilirubin Any Grade | 2 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Bilirubin Grade 3-4 | 0 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Albumin Any Grade | 7 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALP Any Grade | 7 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALP Grade 3-4 | 0 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Creatinine Any Grade | 9 participants |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | AST Any Grade | 5 participants |
Other Pre-specified
Geometric Mean Apparent Volume of Distribution (Vz) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Vz was measured in mL per kilogram body weight (mL/kg). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.
Time frame: Day 1 of Cycle 1 to 28 days post dose
Population: The analyses of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Geometric Mean Apparent Volume of Distribution (Vz) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 59.4 mL/kg | Geometric Coefficient of Variation 30 |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Geometric Mean Apparent Volume of Distribution (Vz) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 54.6 mL/kg | Geometric Coefficient of Variation 20 |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Geometric Mean Apparent Volume of Distribution (Vz) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 61.2 mL/kg | Geometric Coefficient of Variation 43 |
Other Pre-specified
Geometric Mean Total Body Clearance (CLT) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. CLT was measured in mL per hour per kilogram body weight (mL/h/kg). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.
Time frame: Day 1 of Cycle 1 to 28 days post dose
Population: The analyses of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Geometric Mean Total Body Clearance (CLT) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 0.215 mL/h/kg | Geometric Coefficient of Variation 46 |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Geometric Mean Total Body Clearance (CLT) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 0.166 mL/h/kg | Geometric Coefficient of Variation 28 |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Geometric Mean Total Body Clearance (CLT) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 0.195 mL/h/kg | Geometric Coefficient of Variation 54 |
Other Pre-specified
Mean Terminal-phase Elimination Half-life (T-Half) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. T-Half was measured in hours (h). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.
Time frame: Day 1 of Cycle 1 to 28 days post dose
Population: The analyses of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Mean Terminal-phase Elimination Half-life (T-Half) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 204 h | Standard Deviation 134.11 |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Mean Terminal-phase Elimination Half-life (T-Half) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 237 h | Standard Deviation 107.88 |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Mean Terminal-phase Elimination Half-life (T-Half) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 218 h | Standard Deviation 98.87 |
Other Pre-specified
Median Time to Maximal Concentration (Tmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Tmax was measured in hours (h). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.
Time frame: Day 1 of Cycle 1 to 28 days post dose
Population: The analyses of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | Median Time to Maximal Concentration (Tmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 3.23 h |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | Median Time to Maximal Concentration (Tmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 3.87 h |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | Median Time to Maximal Concentration (Tmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method | 3.33 h |