Trial Outcomes & Findings for Phase I Biomarker Study (BMS-936558) (NCT NCT01358721)

NCT ID: NCT01358721

Last Updated: 2021-10-28

Results Overview

The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody in activated and memory T cells with metastatic clear-cell Renal Cell Carcinoma (RCC)

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 119 participants
• Primary outcome timeframe: Baseline, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 8, Cycle 4 Day 1
• Results posted on: 2021-10-28

Participant Flow

119 participants were enrolled, 92 participants were randomized of whom 1 was randomized but not treated. 27 participants did not enter treatment period due to: Participant withdrawal n = 1, Death n = 1, No longer meets criteria n = 22, Other reasons n = 3

Participant milestones

Measure	Nivolumab 0.3 mg/kg (Previously-treated) Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Overall Study STARTED	22	22	23	24
Overall Study COMPLETED	1	0	1	0
Overall Study NOT COMPLETED	21	22	22	24

Reasons for withdrawal

Measure	Nivolumab 0.3 mg/kg (Previously-treated) Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Overall Study Withdrawal by Subject	0	0	0	1
Overall Study Death	0	2	0	0
Overall Study Study Drug Toxicity	1	3	4	5
Overall Study SUBJ request to discontinue study TRT	0	0	0	1
Overall Study Subject No Longer Meets Study Criteria	0	2	0	1
Overall Study Adverse Event related to study drug	1	0	0	1
Overall Study Disease Progression	19	15	17	15
Overall Study Out of State/Unmet Criteria	0	0	1	0

Baseline Characteristics

Phase I Biomarker Study (BMS-936558)

Baseline characteristics by cohort

Measure	Nivolumab 0.3 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) n=23 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) n=24 Participants Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Total n=91 Participants Total of all reporting groups
Age, Continuous	61.0 years STANDARD_DEVIATION .41 • n=5 Participants	60.8 years STANDARD_DEVIATION 9.89 • n=7 Participants	57.7 years STANDARD_DEVIATION 10.98 • n=5 Participants	61.8 years STANDARD_DEVIATION 10.3 • n=4 Participants	60.3 years STANDARD_DEVIATION 10.13 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	10 Participants n=7 Participants	8 Participants n=5 Participants	9 Participants n=4 Participants	30 Participants n=21 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	12 Participants n=7 Participants	15 Participants n=5 Participants	15 Participants n=4 Participants	61 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	19 Participants n=7 Participants	17 Participants n=5 Participants	23 Participants n=4 Participants	75 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	0 Participants n=4 Participants	13 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	21 Participants n=7 Participants	21 Participants n=5 Participants	24 Participants n=4 Participants	86 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 8, Cycle 4 Day 1

Population: All participants in the biomarker data set with baseline measurement and at least one on treatment measurement were included in pharmacodynamic analyses.

The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody in activated and memory T cells with metastatic clear-cell Renal Cell Carcinoma (RCC)

Outcome measures

Measure	Nivolumab 0.3 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) n=23 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) n=24 Participants Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Percent Change From Baseline in Activated and Memory T Cells Cycle 1 Day 1	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells
Percent Change From Baseline in Activated and Memory T Cells Cycle 1 Day 2	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells
Percent Change From Baseline in Activated and Memory T Cells Cycle 1 Day 8	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells
Percent Change From Baseline in Activated and Memory T Cells Cycle 2 Day 8	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells
Percent Change From Baseline in Activated and Memory T Cells Cycle 4 Day 1	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells	NA Percentage Due to improper storage at the central laboratory resulting in poor cell viability, the peripheral blood mononuclear cell (PBMC) samples were unable to be tested for activated and memory T cells

PRIMARY outcome

Timeframe: Baseline, Cycle 1 Day 1 3 Hrs Post, Cycle 1 Day 1 7 Hr Post, Cycle 1 Day 2 24 Hr Post, Cycle 2 Day 1 0 Hr Pre, Cycle 2 Day 8 168 Hrs Post, Cycle 4 Day 1 O Hr Pre (~39 months)

Population: Biomarker evaluable population: All treated participants with at least one measurement for a specific marker were included in the data set for that marker.

Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)

Outcome measures

Measure	Nivolumab 0.3 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) n=23 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) n=24 Participants Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Mean Serum Cytokines: CXCL9 Cycle 1 Day 1, 3 HRSPOST	2859.1 pg/mL Standard Deviation 2481.44	2294.3 pg/mL Standard Deviation 1528.97	1906.6 pg/mL Standard Deviation 1744.09	2203.6 pg/mL Standard Deviation 1728.76
Mean Serum Cytokines: CXCL9 Cycle 1 Day 1, 7HRSPOST	3287.7 pg/mL Standard Deviation 3617.32	2567.1 pg/mL Standard Deviation 1885.13	2546.1 pg/mL Standard Deviation 2421.00	2883.6 pg/mL Standard Deviation 2827.77
Mean Serum Cytokines: CXCL9 Cycle 1 Day 2, 24 HRSPOST	5447.3 pg/mL Standard Deviation 7006.73	4332.3 pg/mL Standard Deviation 3875.12	4216.4 pg/mL Standard Deviation 4715.61	3858.80 pg/mL Standard Deviation 2841.7
Mean Serum Cytokines: CXCL9 Cycle 2 Day 1, 0 HRSPRE	5192.6 pg/mL Standard Deviation 4447.78	7220.6 pg/mL Standard Deviation 9385.90	5398.8 pg/mL Standard Deviation 5428.64	5687.4 pg/mL Standard Deviation 6788.78
Mean Serum Cytokines: CXCL9 Cycle 2 Day 8, 168 HRSPOST	5271.5 pg/mL Standard Deviation 5196.91	4932.6 pg/mL Standard Deviation 4321.91	5751.3 pg/mL Standard Deviation 5900.87	5773.2 pg/mL Standard Deviation 6560.9
Mean Serum Cytokines: CXCL9 Cycle 4 Day 1, 0 HRSPRE	8519.4 pg/mL Standard Deviation 11444.72	5131.2 pg/mL Standard Deviation 4330.84	3523.6 pg/mL Standard Deviation 2678.32	5449.5 pg/mL Standard Deviation 4021.84
Mean Serum Cytokines: CXCL9 BASELINE	2681.6 pg/mL Standard Deviation 2135.89	2213.5 pg/mL Standard Deviation 1520.44	2065.3 pg/mL Standard Deviation 1805.25	2610.6 pg/mL Standard Deviation 2118.11

PRIMARY outcome

Timeframe: Baseline, Cycle 1 Day 1 3 Hrs Post, Cycle 1 Day 1 7 Hr Post, Cycle 1 Day 2 24 Hr Post, Cycle 2 Day 1 0 Hr Pre, Cycle 2 Day 8 168 Hrs Post, Cycle 4 Day 1 O Hr Pre (~39 months)

Population: Biomarker evaluable population: All treated participants with at least one measurement for a specific marker were included in the data set for that marker.

Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)

Outcome measures

Measure	Nivolumab 0.3 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) n=23 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) n=24 Participants Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Mean Serum Cytokines CXCL10 (IP10) Cycle 1 Day 1, 3 HRSPOST	525.5 pg/mL Standard Deviation 335.10	523.4 pg/mL Standard Deviation 400.88	422.0 pg/mL Standard Deviation 264.54	450.7 pg/mL Standard Deviation 247.78
Mean Serum Cytokines CXCL10 (IP10) Cycle 1 Day 1, 7HRSPOST	591.4 pg/mL Standard Deviation 360.30	727.7 pg/mL Standard Deviation 626.98	762.2 pg/mL Standard Deviation 896.22	531.4 pg/mL Standard Deviation 508.20
Mean Serum Cytokines CXCL10 (IP10) Cycle 1 Day 2, 24 HRSPOST	813.2 pg/mL Standard Deviation 547.71	758.8 pg/mL Standard Deviation 616.06	736.1 pg/mL Standard Deviation 787.53	700.5 pg/mL Standard Deviation 738.71
Mean Serum Cytokines CXCL10 (IP10) Cycle 2 Day 1, 0 HRSPRE	718.0 pg/mL Standard Deviation 471.22	835.9 pg/mL Standard Deviation 579.07	781.9 pg/mL Standard Deviation 753.41	679.4 pg/mL Standard Deviation 556.47
Mean Serum Cytokines CXCL10 (IP10) Cycle 2 Day 8, 168 HRSPOST	724.1 pg/mL Standard Deviation 470.03	677.6 pg/mL Standard Deviation 341.15	794.6 pg/mL Standard Deviation 882.64	770.6 pg/mL Standard Deviation 672.43
Mean Serum Cytokines CXCL10 (IP10) Cycle 4 Day 1, 0 HRSPRE	1272.8 pg/mL Standard Deviation 2075.49	678.7 pg/mL Standard Deviation 364.85	431.3 pg/mL Standard Deviation 133.78	794.8 pg/mL Standard Deviation 574.14
Mean Serum Cytokines CXCL10 (IP10) BASELINE	474.5 pg/mL Standard Deviation 236.75	483.0 pg/mL Standard Deviation 383.77	397.4 pg/mL Standard Deviation 223.89	767.9 pg/mL Standard Deviation 525.06

PRIMARY outcome

Timeframe: Cycle 2 Day 8 168 Hr post dose

Population: Biomarker evaluable population: All treated participants with at least one measurement for a specific marker were included in the data set for that marker.

The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody on circulating CD4 infiltrations in tumors in participants with metastatic clear-cell Renal Cell Carcinoma (RCC).

Outcome measures

Measure	Nivolumab 0.3 mg/kg (Previously-treated) n=18 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) n=20 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) n=14 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) n=16 Participants Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Mean CD4 T Cell Infiltration Baseline	34.1 Number of CD4+ Cells Standard Deviation 78.40	10.4 Number of CD4+ Cells Standard Deviation 34.38	35.2 Number of CD4+ Cells Standard Deviation 77.44	53.2 Number of CD4+ Cells Standard Deviation 109.31
Mean CD4 T Cell Infiltration Cycle 2 Day 8, 168 HrsPost	64.8 Number of CD4+ Cells Standard Deviation 77.22	28.2 Number of CD4+ Cells Standard Deviation 46.93	53.4 Number of CD4+ Cells Standard Deviation 97.98	107.4 Number of CD4+ Cells Standard Deviation 254.75

PRIMARY outcome

Timeframe: 168 hour post does Cycle 2 Day 8 in evaluable participates (First active dose of study medication to cycle two day eight post injection)

Population: Biomarker evaluable population: All treated participants at least one measurement for a specific marker were included in the data set for that marker.

The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody on circulating CD8 infiltrations in tumors in participants with metastatic clear-cell Renal Cell Carcinoma (RCC).

Outcome measures

Measure	Nivolumab 0.3 mg/kg (Previously-treated) n=18 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) n=20 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) n=14 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) n=16 Participants Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Mean CD8 T Cell Infiltration Baseline	10.2 Number of CD8 cells Standard Deviation 13.77	7.8 Number of CD8 cells Standard Deviation 10.62	11.9 Number of CD8 cells Standard Deviation 14.31	14.4 Number of CD8 cells Standard Deviation 18.37
Mean CD8 T Cell Infiltration Cycle 2 Day 8, 169 HRSPOST	14.9 Number of CD8 cells Standard Deviation 13.85	18.9 Number of CD8 cells Standard Deviation 17.07	23.3 Number of CD8 cells Standard Deviation 23.49	16.3 Number of CD8 cells Standard Deviation 22.19

SECONDARY outcome

Timeframe: Assessed at a minimum of every 3 weeks up to 70 days following discontinuation of study drug (up to approximately 39 months)

Population: All treated participants

Baseline and post-nivolumab treatment modulation of serum levels of interferon-gamma stimulated chemokines CXCL9 and CXCL10 (IP10) were assessed. The participant's best response designation over the study as a whole, recorded between the date of first study drug administration and the date of objectively documented progression per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Outcome measures

Measure	Nivolumab 0.3 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) n=23 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) n=24 Participants Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Best Overall Response in the BMS-936558 Arms Complete Response	0 Participants	0 Participants	0 Participants	2 Participants
Best Overall Response in the BMS-936558 Arms Partial Response	2 Participants	4 Participants	5 Participants	1 Participants
Best Overall Response in the BMS-936558 Arms Stable Disease	8 Participants	10 Participants	11 Participants	13 Participants
Best Overall Response in the BMS-936558 Arms Progressive Disease	9 Participants	5 Participants	6 Participants	7 Participants
Best Overall Response in the BMS-936558 Arms Unable To Determine	2 Participants	3 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Progression free survival rate will be assessed in each individual treatment arm by tumor assessments at 16, 24, and 48 weeks. From initial dose to end of study (assessed up to 39 months)

Population: All treated participants

PFS is defined as the time from treatment arm assignment to the date of first documented disease progression. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment. Participants who did not have any on study tumor assessments will be censored on the date they were assigned a treatment arm. PFS rate is the percentage of participants who did not have disease progression at particular time points (16 weeks, 24 weeks, 48 weeks)

Outcome measures

Measure	Nivolumab 0.3 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) n=23 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) n=24 Participants Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Progression Free Survival Rate in BMS-936558 16 weeks	0.29 percent Interval 0.12 to 0.48	0.49 percent Interval 0.27 to 0.68	0.63 percent Interval 0.39 to 0.79	0.55 percent Interval 0.32 to 0.72
Progression Free Survival Rate in BMS-936558 24 weeks	0 percent Interval 0.0 to 0.0	0.44 percent Interval 0.23 to 0.63	0.58 percent Interval 0.35 to 0.76	0.50 percent Interval 0.28 to 0.68
Progression Free Survival Rate in BMS-936558 48 weeks	0 percent Interval 0.0 to 0.0	0 percent Interval 0.0 to 0.0	0.32 percent Interval 0.13 to 0.52	0.39 percent Interval 0.18 to 0.59

SECONDARY outcome

Timeframe: Up to 22 months after study start

Population: All treated participants

The total number of subjects whose best overall response (BOR) is either a complete response (CR) or partial response (PR) divided by the total number of participants in the population of interest, and expressed as a percentage.

Outcome measures

Measure	Nivolumab 0.3 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) n=23 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) n=24 Participants Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Objective Response Rate in BMS-936558	9.1 percent Interval 1.1 to 29.2	18.2 percent Interval 5.2 to 40.3	21.7 percent Interval 7.5 to 43.7	12.5 percent Interval 2.7 to 32.4

SECONDARY outcome

Timeframe: The time when the measurement criteria are first met for PR or CR (whichever is reported first) until the date of documented disease progression or death (assessed up to 39 months)

Population: All treated participants

The duration of response is defined as the time when the measurement criteria are first met for PR or CR (whichever is reported first) until the date of documented disease progression or death. For subjects who neither progress nor die, the duration of response will be censored at the date of their last tumor assessment.

Outcome measures

Measure	Nivolumab 0.3 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) n=23 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) n=24 Participants Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Duration of Objective Response for BMS-936558	30 weeks Interval 24.1 to 35.9	NA weeks NA=Not Reached due to a high percentage of ongoing responders	48.1 weeks Interval 12.0 to NA=Not Reached due to a high percentage of ongoing responders	NA weeks NA=Not Reached due to a high percentage of ongoing responders

SECONDARY outcome

Timeframe: The time from treatment arm assignment until the criteria for progression are met or death (whichever occurs first)(assessed up to 39 months)

Population: All treated participants

Duration of stable disease (SD) is defined in participants whose BOR is SD at the time from treatment arm assignment until the criteria for progression are met or death (whichever occurs first). Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment

Outcome measures

Measure	Nivolumab 0.3 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) n=23 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) n=24 Participants Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Duration of Stable Disease for BMS-936558 as Measured in Participants Whose Best Overall Response is Stable Disease as the Time From Baseline Until the Date of Documented Disease Progression or Death	16.5 weeks Interval 11.6 to 36.3	31.4 weeks Interval 10.7 to Upper limit not reached	41.3 weeks Interval 12.1 to 75.6	35.1 weeks Interval 12.3 to 53.4

SECONDARY outcome

Timeframe: Pre-dose, Cycle 4 Day 1, Cycle 8 Day 1 and during follow-up.

Population: ADA-Positive Subject: A subject with at least one ADA-positive sample at any time after initiation of treatment. ADA-Negative Subject: A subject with no ADA-positive sample after the initiation of treatment

Blood samples to evaluate the development of a positive anti-drug antibodies (ADA) response at the doses tested will be collected at time-points pre-dose, C4D1, C8D1 and during follow-up.

Outcome measures

Measure	Nivolumab 0.3 mg/kg (Previously-treated) n=17 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 2 mg/kg (Previously-treated) n=19 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Previously-treated) n=22 Participants Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	Nivolumab 10 mg/kg (Treatment-naive) n=21 Participants Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Immunogenicity of BMS-936558 as Measured by the Detection of Human Antibodies Against BMS-936558 Anti-Drug Antibody (ADA) positive (%)	11.8 percentage	15.8 percentage	13.6 percentage	0 percentage
Immunogenicity of BMS-936558 as Measured by the Detection of Human Antibodies Against BMS-936558 Anti-Drug Antibody (ADA) negative(%)	88.2 percentage	84.2 percentage	86.4 percentage	100 percentage

Adverse Events

BMS 0.3 mg/kg

Serious events: 13 serious events

Other events: 22 other events

Deaths: 0 deaths

BMS 2 mg/kg

Serious events: 11 serious events

Other events: 22 other events

Deaths: 0 deaths

BMS 10 mg/kg

Serious events: 12 serious events

Other events: 23 other events

Deaths: 0 deaths

BMS 10 mg/Kg-N

Serious events: 13 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Measure	BMS 0.3 mg/kg n=22 participants at risk Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	BMS 2 mg/kg n=22 participants at risk Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	BMS 10 mg/kg n=23 participants at risk Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	BMS 10 mg/Kg-N n=24 participants at risk Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Cardiac disorders Atrial flutter	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Eye disorders Papilloedema	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Colitis	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Constipation	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Enteritis	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Small intestinal haemorrhage	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
General disorders Pain	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
General disorders Pyrexia	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
General disorders Sudden death	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Infections and infestations Urinary tract infection	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Infections and infestations Viral upper respiratory tract infection	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Injury, poisoning and procedural complications Fall	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Injury, poisoning and procedural complications Femur fracture	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Injury, poisoning and procedural complications Fracture	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Investigations Alanine aminotransferase increased	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Investigations Aspartate aminotransferase increased	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Investigations Blood bilirubin increased	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Flank pain	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Polyarthritis	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	18.2% 4/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	12.5% 3/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to testicle	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Central nervous system necrosis	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Cerebral haemorrhage	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Tremor	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Renal and urinary disorders Acute kidney injury	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Renal and urinary disorders Renal colic	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Renal and urinary disorders Renal failure	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Renal and urinary disorders Renal mass	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Pneumonitis	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Vascular disorders Deep vein thrombosis	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Vascular disorders Embolism	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Haematemesis	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Hepatobiliary disorders Bile duct obstruction	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Infections and infestations Sepsis	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Infections and infestations Septic shock	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Injury, poisoning and procedural complications Thermal burn	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Injury, poisoning and procedural complications Toxicity to various agents	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Investigations Amylase increased	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Investigations Blood alkaline phosphatase increased	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Investigations Blood creatinine increased	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Metabolism and nutrition disorders Dehydration	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Ataxia	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Facial nerve disorder	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Ischaemic stroke	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Paralysis	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Vascular disorders Thrombosis	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)

Other adverse events

Measure	BMS 0.3 mg/kg n=22 participants at risk Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	BMS 2 mg/kg n=22 participants at risk Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	BMS 10 mg/kg n=23 participants at risk Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study.	BMS 10 mg/Kg-N n=24 participants at risk Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study.
Blood and lymphatic system disorders Anaemia	27.3% 6/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	26.1% 6/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	16.7% 4/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Endocrine disorders Hypothyroidism	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	17.4% 4/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Eye disorders Eye pruritus	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Eye disorders Vision blurred	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Abdominal discomfort	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Abdominal distension	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Abdominal pain	27.3% 6/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	20.8% 5/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Abdominal pain upper	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Constipation	31.8% 7/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	27.3% 6/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	21.7% 5/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	25.0% 6/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Diarrhoea	18.2% 4/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	18.2% 4/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	21.7% 5/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	37.5% 9/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Dry mouth	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	20.8% 5/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Dyspepsia	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Nausea	36.4% 8/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	31.8% 7/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	26.1% 6/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	41.7% 10/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Gastrointestinal disorders Vomiting	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	18.2% 4/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	12.5% 3/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
General disorders Asthenia	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	17.4% 4/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
General disorders Chest pain	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
General disorders Chills	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	16.7% 4/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
General disorders Fatigue	54.5% 12/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	59.1% 13/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	65.2% 15/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	54.2% 13/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
General disorders Mucosal inflammation	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	12.5% 3/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
General disorders Oedema peripheral	18.2% 4/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	30.4% 7/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	12.5% 3/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
General disorders Pain	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	18.2% 4/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	17.4% 4/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
General disorders Pyrexia	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Infections and infestations Cellulitis	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Infections and infestations Rash pustular	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Infections and infestations Rhinitis	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Infections and infestations Sinusitis	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	12.5% 3/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Infections and infestations Upper respiratory tract infection	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	16.7% 4/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Infections and infestations Urinary tract infection	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Infections and infestations Viral upper respiratory tract infection	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Injury, poisoning and procedural complications Fall	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Injury, poisoning and procedural complications Infusion related reaction	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	17.4% 4/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	16.7% 4/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Investigations Alanine aminotransferase increased	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Investigations Aspartate aminotransferase increased	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Investigations Blood alkaline phosphatase increased	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Investigations Blood bilirubin increased	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Investigations Blood creatinine increased	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	18.2% 4/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Investigations Weight decreased	27.3% 6/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Metabolism and nutrition disorders Decreased appetite	31.8% 7/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	20.8% 5/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Metabolism and nutrition disorders Dehydration	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	16.7% 4/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Metabolism and nutrition disorders Hypercalcaemia	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	12.5% 3/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Metabolism and nutrition disorders Hyperkalaemia	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Metabolism and nutrition disorders Hypokalaemia	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Metabolism and nutrition disorders Hyponatraemia	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Arthralgia	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	26.1% 6/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	37.5% 9/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Back pain	18.2% 4/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	21.7% 5/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	33.3% 8/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Flank pain	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Muscular weakness	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	16.7% 4/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Myalgia	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Musculoskeletal and connective tissue disorders Pain in extremity	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	12.5% 3/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Dizziness	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	16.7% 4/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Dysgeusia	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	12.5% 3/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Headache	18.2% 4/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	22.7% 5/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Hypoaesthesia	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Nervous system disorders Restless legs syndrome	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Psychiatric disorders Depression	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Psychiatric disorders Insomnia	18.2% 4/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Psychiatric disorders Mental status changes	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Renal and urinary disorders Haematuria	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Renal and urinary disorders Urinary retention	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Cough	31.8% 7/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	36.4% 8/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	17.4% 4/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	20.8% 5/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Dysphonia	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	16.7% 4/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	22.7% 5/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	20.8% 5/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Nasal congestion	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	12.5% 3/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	13.0% 3/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	12.5% 3/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Skin and subcutaneous tissue disorders Dry skin	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.3% 1/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	12.5% 3/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Skin and subcutaneous tissue disorders Hyperhidrosis	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Skin and subcutaneous tissue disorders Pruritus	13.6% 3/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	18.2% 4/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	17.4% 4/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	16.7% 4/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Skin and subcutaneous tissue disorders Rash	22.7% 5/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Skin and subcutaneous tissue disorders Rash pruritic	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	0.00% 0/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	4.2% 1/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)
Vascular disorders Hypertension	4.5% 1/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	9.1% 2/22 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.7% 2/23 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)	8.3% 2/24 • From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months)

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: Clinical.Trials@bms.com

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