Trial Outcomes & Findings for Japanese Study of BMS-901608 (Elotuzumab) in Combination With Lenalidomide and Low Dose Dexamethasone (NCT NCT01241292)

Last Updated: 2018-02-15

Results Overview

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. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Data cut-off February 2014.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

7 participants

Primary outcome timeframe

First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Results posted on

2018-02-15

Participant Flow

Seven participants were enrolled and 6 entered the treatment period. Reason for 1 participant not entering treatment period: participant no longer met study criteria.

Participant milestones

Participant milestones
Measure	Elotuzumab 10 mg/kg Elotuzumab 10 mg/kg was intravenously (IV) given weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity. Elotuzumab was first given at 10 mg/kg. If all participants completed the first cycle and none experienced a dose limiting toxicity (DLT), the dose was escalated to 20 mg/kg. If 1 experienced a DLT at 10 mg/kg, 3 additional participants were assigned to 10 mg/kg. If no additional participants experienced a DLT, the dose was escalated to 20 mg/kg. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. On weeks without elotuzumab, dexamethasone was administered as a single oral (PO) dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (3 to 24 hours prior to the start of elotuzumab) and 8 mg IV (45 min prior to start of elotuzumab).	Elotuzumab 20 mg/kg Elotuzumab 20 mg/kg was intravenously (IV) given weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity. Elotuzumab was first given at 10 mg/kg. If all participants completed the first cycle and none experienced a dose limiting toxicity (DLT), the dose was escalated to 20 mg/kg. If 1 experienced a DLT at 10 mg/kg, 3 additional participants were assigned to 10 mg/kg. If no additional participants experienced a DLT, the dose was escalated to 20 mg/kg. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. On weeks without elotuzumab, dexamethasone was administered as a single oral (PO) dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (3 to 24 hours prior to the start of elotuzumab) and 8 mg IV (45 min prior to start of elotuzumab).
Overall Study STARTED	3	3
Overall Study Entered Treatment Period	3	3
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Elotuzumab 10 mg/kg Elotuzumab 10 mg/kg was intravenously (IV) given weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity. Elotuzumab was first given at 10 mg/kg. If all participants completed the first cycle and none experienced a dose limiting toxicity (DLT), the dose was escalated to 20 mg/kg. If 1 experienced a DLT at 10 mg/kg, 3 additional participants were assigned to 10 mg/kg. If no additional participants experienced a DLT, the dose was escalated to 20 mg/kg. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. On weeks without elotuzumab, dexamethasone was administered as a single oral (PO) dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (3 to 24 hours prior to the start of elotuzumab) and 8 mg IV (45 min prior to start of elotuzumab).	Elotuzumab 20 mg/kg Elotuzumab 20 mg/kg was intravenously (IV) given weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity. Elotuzumab was first given at 10 mg/kg. If all participants completed the first cycle and none experienced a dose limiting toxicity (DLT), the dose was escalated to 20 mg/kg. If 1 experienced a DLT at 10 mg/kg, 3 additional participants were assigned to 10 mg/kg. If no additional participants experienced a DLT, the dose was escalated to 20 mg/kg. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. On weeks without elotuzumab, dexamethasone was administered as a single oral (PO) dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (3 to 24 hours prior to the start of elotuzumab) and 8 mg IV (45 min prior to start of elotuzumab).
Overall Study Administrative Reason by Sponsor	1	0
Overall Study Disease Progression	2	0
Overall Study Study Drug Toxicity	0	1
Overall Study Participant Discontinued Treatment	0	2

Baseline Characteristics

Japanese Study of BMS-901608 (Elotuzumab) in Combination With Lenalidomide and Low Dose Dexamethasone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Elotuzumab 10 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab 20 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Total n=6 Participants Total of all reporting groups
Age, Continuous	61.0 years n=99 Participants	66.0 years n=107 Participants	63.5 years n=206 Participants
Age, Customized Less than (<) 65	2 participants n=99 Participants	1 participants n=107 Participants	3 participants n=206 Participants
Age, Customized 65 to < 75	1 participants n=99 Participants	1 participants n=107 Participants	2 participants n=206 Participants
Age, Customized Greater than, equal to 75	0 participants n=99 Participants	1 participants n=107 Participants	1 participants n=206 Participants
Sex: Female, Male Female	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants
Sex: Female, Male Male	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Region of Enrollment Japan	3 participants n=99 Participants	3 participants n=107 Participants	6 participants n=206 Participants

PRIMARY outcome

Timeframe: First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Population: All participants who received at least one dose of study medication were summarized (Treated Participants).

Outcome measures

Outcome measures
Measure	Elotuzumab 10 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab 20 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths Grade 3-4 AEs	3 participants	3 participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths All SAEs Any Grade	2 participants	3 participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths Grade 3-4 SAEs	1 participants	3 participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths AEs Leading to Discontinuation	0 participants	1 participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths Deaths	0 participants	0 participants

PRIMARY outcome

Timeframe: First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Population: All participants who received at least one dose of study medication were summarized.

Vital signs (body temperature, seated blood pressure, heart rate, and respiration rate) were recorded at screening on Days 1, 8, 15, and 22 of Cycles 1 and 2, on Days 1 and 15 of Cycle 3, and at the end of treatment. Blood pressure (Diastolic and Systolic) and heart rate were recorded after the participant sat quietly for at least 5 minutes. Clinical relevance of vital sign data was determined by the investigator.

Outcome measures

Outcome measures
Measure	Elotuzumab 10 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab 20 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Number of Participants With Clinically Relevant Vital Sign Findings	0 participants	0 participants

PRIMARY outcome

Timeframe: First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Population: All participants who received at least one dose of study medication were summarized.

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) 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 (absolute): 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.

Outcome measures

Outcome measures
Measure	Elotuzumab 10 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab 20 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Hemoglobin Any Grade	3 participants	3 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Hemoglobin Grade 3-4	0 participants	1 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Lymphocytes Any Grade	3 participants	3 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Lymphocytes Grade 3-4	3 participants	3 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Neutrophils Any Grade	3 participants	3 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Neutrophils Grade 3-4	2 participants	3 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Platelet Count Any Grade	3 participants	2 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Platelet Count Grade 3-4	1 participants	0 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Leukocytes Any Grade	3 participants	3 participants
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests Leukocytes Grade 3-4	2 participants	1 participants

PRIMARY outcome

Timeframe: First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Population: All participants who received at least one dose of study medication were summarized.

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). 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.

Outcome measures

Outcome measures
Measure	Elotuzumab 10 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab 20 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests Albumin Any Grade	3 participants	3 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests Albumin Grade 3-4	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests ALP Any Grade	1 participants	2 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests ALP Grade 3-4	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests ALT Any Grade	2 participants	2 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests ALT Grade 3-4	1 participants	1 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests AST Any Grade	1 participants	2 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests AST Grade 3-4	1 participants	1 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests Creatinine Any Grade	0 participants	2 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests Creatinine Grade 3-4	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests Bilirubin Total Any Grade	1 participants	0 participants
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests Bilirubin Total Grade 3-4	0 participants	0 participants

PRIMARY outcome

Timeframe: First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Population: All participants who received at least one dose of study medication were summarized.

NCI CTCAE, version 3.0 was used to measure toxicity scale. 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 - Gr 2: \<LLN - 3.0; Gr 3: \< 3.0 - 2.5; Gr 4: \<2.5 mmol/L.

Outcome measures

Outcome measures
Measure	Elotuzumab 10 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab 20 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Sodium Low, Grade 3-4	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Potassium High, Any Grade	0 participants	2 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Potassium High, Grade 3-4	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Potassium Low, Any Grade	3 participants	2 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Potassium Low, Grade 3-4	0 participants	1 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Sodium High, Any Grade	1 participants	2 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Sodium High, Grade 3-4	0 participants	0 participants
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests Sodium Low, Any Grade	2 participants	3 participants

SECONDARY outcome

Timeframe: Cycle 2 (Study Day 29) to last dose (assessed up to January 2017, approximately 71 months)

Population: All participants who received at least one dose of study medication were summarized (Treated Participants).

Complete response (CR) and Partial Response (PR) were based on the European Group for Blood and Bone Marrow Transplant (EBMT) Criteria. Very Good Partial response was derived from the International Myeloma Working Group (IMWG) criteria. Participants who had a reduction in M-protein or plasmacytoma but did not meet the EBMT criteria for PR were classified as minimal response (MR). Hematologic, radiologic and/or clinical assessments were done every cycle starting with cycle 2. Each cycle is 4 weeks in length (Day 1, Day 8, Day 15, Day 22). Cycle 2 began on study Day 29. CR=negative immunofixation 6 weeks, \<5% plasma cells, no increase in size or number of lytic lesions, complete disappearance of extramedullary plasmacytoma. PR=≥50%reduction in M-protein for 6 weeks, ≥90% reduction of urinary light chain excretion or \< 200 mg/24hours for 6 weeks, ≥50% reduction in size of extramedullary plasmacytoma present at baseline, no increase in size or number of lytic lesions.

Outcome measures

Outcome measures
Measure	Elotuzumab 10 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab 20 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Number of Participants With Best Overall Response - Treated Participants Complete Response	0 participants	1 participants
Number of Participants With Best Overall Response - Treated Participants Very Good Partial Response	1 participants	2 participants
Number of Participants With Best Overall Response - Treated Participants Partial Response	1 participants	0 participants
Number of Participants With Best Overall Response - Treated Participants Minimal Response	1 participants	0 participants

SECONDARY outcome

Timeframe: Days 1, 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3

Population: All participants who received at least one dose of study medication and had adequate Pharmacokinetic (PK) concentration profiles were summarized.

The quantification of elotuzumab in human serum was performed using a validated enzyme-linked immunosorbent assay (ELISA). Cmax was measured in micrograms per milliliter (µg/mL). Samples of serum were obtained at: Cycle 1, Day 1: 0 hour (h), 30 minutes (min) 2 h post dose; Day 8: 0h, 2 h; Day 15: 0h, 30 min; Day 22: 0h, 30min, 2h. Cycle 2, Day 1, 22 0h, 2h. Cycle 3, Day 1: 0h, 30h, 2h; Day 15: 0h.

Outcome measures

Outcome measures
Measure	Elotuzumab 10 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab 20 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 Cycle 1 Day 1 (n=3,3)	173 µg/mL Geometric Coefficient of Variation 9	376 µg/mL Geometric Coefficient of Variation 14
Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 Cycle 1 Day 8 (n=3,3)	237 µg/mL Geometric Coefficient of Variation 19	549 µg/mL Geometric Coefficient of Variation 18
Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 Cycle 1 Day 15 (n=3,3)	297 µg/mL Geometric Coefficient of Variation 10	652 µg/mL Geometric Coefficient of Variation 21
Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 Cycle 1 Day 22 (n=3,2)	234 µg/mL Geometric Coefficient of Variation 14	724 µg/mL Geometric Coefficient of Variation 45
Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 Cycle 2 Day 1 (n=3,3)	240 µg/mL Geometric Coefficient of Variation 28	671 µg/mL Geometric Coefficient of Variation 51
Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 Cycle 2 Day 22 (n=3,3)	270 µg/mL Geometric Coefficient of Variation 32	844 µg/mL Geometric Coefficient of Variation 26
Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 Cycle 3 Day 1 (n=3,3)	286 µg/mL Geometric Coefficient of Variation 32	972 µg/mL Geometric Coefficient of Variation 32

SECONDARY outcome

Timeframe: Days 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3

Population: All participants who received at least one dose of study medication and had adequate PK concentration profiles were summarized.

The quantification of elotuzumab in human serum was performed using a validated enzyme-linked immunosorbent assay (ELISA). Cmin was measured in micrograms per milliliter (µg/mL). Samples of serum were obtained at: Cycle 1, Day 1: 0 hour (h), 30 minutes (min) 2 h post dose; Day 8: 0h, 2 h; Day 15: 0h, 30 min; Day 22: 0h, 30min, 2h. Cycle 2, Day 1, 22 0h, 2h. Cycle 3, Day 1: 0h, 30h, 2h; Day 15: 0h.

Outcome measures

Outcome measures
Measure	Elotuzumab 10 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab 20 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 Cycle 1 Day 8 (n=3,3)	59.1 µg/mL Geometric Coefficient of Variation 28	165 µg/mL Geometric Coefficient of Variation 20
Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 Cycle 1 Day 15 (n=3,3)	97.0 µg/mL Geometric Coefficient of Variation 12	252 µg/mL Geometric Coefficient of Variation 30
Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 Cycle 1 Day 22 (n=3,2)	24.6 µg/mL Geometric Coefficient of Variation 87	280 µg/mL Geometric Coefficient of Variation 62
Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 Cycle 2 Day 1 (n=3,2)	25.8 µg/mL Geometric Coefficient of Variation 95	389 µg/mL Geometric Coefficient of Variation 64
Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 Cycle 2 Day 22 (n=3,3)	57.8 µg/mL Geometric Coefficient of Variation 82	547 µg/mL Geometric Coefficient of Variation 41
Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 Cycle 3 Day 1 (n=3,3)	77.2 µg/mL Geometric Coefficient of Variation 78	579 µg/mL Geometric Coefficient of Variation 46
Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 Cycle 3 Day 15 (n=3,3)	59.4 µg/mL Geometric Coefficient of Variation 78	466 µg/mL Geometric Coefficient of Variation 38

SECONDARY outcome

Timeframe: First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Population: All participants who received at least one dose of study medication were summarized.

The detection of anti-elotuzumab anti-drug antibodies (ADAs) in human serum was performed using a validated bridging electrochemiluminescence immunoassay (ECLA) on the Meso Scale Discovery (MSD) platform. Sample collection was performed prior to administration of elotuzumab at Day 1 of each cycle.

Outcome measures

Outcome measures
Measure	Elotuzumab 10 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab 20 mg/kg n=3 Participants Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Number of Participants Positive for Anti-Elotuzumab Anti-drug Antibodies - Treated Participants	3 participants	0 participants

Adverse Events

BMS 10mg/kg + Ld

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

BMS 20mg/kg + Ld

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	BMS 10mg/kg + Ld n=3 participants at risk	BMS 20mg/kg + Ld n=3 participants at risk
Eye disorders Cataract	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Hepatobiliary disorders Cholelithiasis	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Hepatobiliary disorders Hepatitis	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Infections and infestations Pneumonia	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Alanine aminotransferase increased	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Aspartate aminotransferase increased	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Blood alkaline phosphatase increased	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Gamma-glutamyltransferase increased	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	BMS 10mg/kg + Ld n=3 participants at risk	BMS 20mg/kg + Ld n=3 participants at risk
Nervous system disorders Neuropathy peripheral	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Nervous system disorders Somnolence	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Psychiatric disorders Insomnia	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Blood and lymphatic system disorders Anaemia	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Blood and lymphatic system disorders Granulocytopenia	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Blood and lymphatic system disorders Leukopenia	100.0% 3/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	100.0% 3/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Blood and lymphatic system disorders Lymphopenia	100.0% 3/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	100.0% 3/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Blood and lymphatic system disorders Neutropenia	100.0% 3/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Blood and lymphatic system disorders Thrombocytopenia	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Cardiac disorders Atrioventricular block first degree	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Eye disorders Cataract	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Eye disorders Conjunctival haemorrhage	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Eye disorders Eye discharge	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Gastrointestinal disorders Constipation	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Gastrointestinal disorders Dental caries	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Gastrointestinal disorders Diarrhoea	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Gastrointestinal disorders Epigastric discomfort	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Gastrointestinal disorders Eructation	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Gastrointestinal disorders Gingival erosion	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Gastrointestinal disorders Nausea	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Gastrointestinal disorders Proctalgia	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Gastrointestinal disorders Stomatitis	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Gastrointestinal disorders Vomiting	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
General disorders Chest pain	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
General disorders Fatigue	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
General disorders Malaise	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
General disorders Oedema	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
General disorders Pyrexia	100.0% 3/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Immune system disorders Seasonal allergy	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Infections and infestations Cystitis	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Infections and infestations Herpes simplex	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Infections and infestations Herpes zoster	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Infections and infestations Infection	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Infections and infestations Influenza	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Infections and infestations Nasopharyngitis	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Infections and infestations Oral fungal infection	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Infections and infestations Periodontitis	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Infections and infestations Pneumonia	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Injury, poisoning and procedural complications Arthropod sting	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Injury, poisoning and procedural complications Contusion	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Injury, poisoning and procedural complications Laceration	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Injury, poisoning and procedural complications Wound	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Alanine aminotransferase increased	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Amylase increased	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Aspartate aminotransferase increased	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Blood alkaline phosphatase increased	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Blood creatine phosphokinase increased	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Creatinine renal clearance decreased	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Electrocardiogram qt prolonged	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Haemoglobin decreased	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Investigations Weight decreased	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Metabolism and nutrition disorders Glucose tolerance impaired	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Metabolism and nutrition disorders Hypertriglyceridaemia	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Musculoskeletal and connective tissue disorders Back pain	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Nervous system disorders Dizziness	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Nervous system disorders Dysgeusia	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	100.0% 3/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Nervous system disorders Headache	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Respiratory, thoracic and mediastinal disorders Hiccups	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Skin and subcutaneous tissue disorders Haemorrhage subepidermal	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Skin and subcutaneous tissue disorders Penile ulceration	33.3% 1/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Skin and subcutaneous tissue disorders Rash	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Vascular disorders Flushing	0.00% 0/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)	66.7% 2/3 • First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)