Trial Outcomes & Findings for A Study of MDX-1106 in Patients With Selected Refractory or Relapsed Malignancies (NCT NCT00441337)

NCT ID: NCT00441337

Last Updated: 2015-02-20

Results Overview

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Severe=All Grade 3 or 4 events. Death=during the study and up to 28 days past study discontinuation. AEs graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. irAEs=unknown etiology, associated with study drug and consistent with an immune phenomenon. DLT: ≥Gr 3 AE(s) or lab abnormality without alternative explanation other than drug.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 39 participants
• Primary outcome timeframe: Day 1 to 70 days post last dose of study drug; 28 days past study discontinuation
• Results posted on: 2015-02-20

Participant Flow

Study from 25 October 2006 to 27 November 2009. After completion of a single dose (cycle 1), those meeting criteria could be re-treated with 2 additional doses (cycle 2); and additional cycles. Participants who had a complete response (CR) or partial response (PR) at end of re-treatment were followed-up until disease progression for 2 years.

39 participants were enrolled and 39 were treated with at least 1 dose or a partial dose of study drug.

Participant milestones

Measure	0.3 mg/kg Nivolumab 0.3 milligrams (mg) of nivolumab per kilogram (kg) of body weight (mg/kg) was administered in a single intravenous (IV) infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Overall Study STARTED	6	6	6	21
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	6	6	6	21

Reasons for withdrawal

Measure	0.3 mg/kg Nivolumab 0.3 milligrams (mg) of nivolumab per kilogram (kg) of body weight (mg/kg) was administered in a single intravenous (IV) infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Overall Study Disease Progression	6	6	4	18
Overall Study Lost to Follow-up	0	0	0	1
Overall Study Sponsor Decision	0	0	1	2
Overall Study Did not meet inclusion criteria	0	0	1	0

Baseline Characteristics

A Study of MDX-1106 in Patients With Selected Refractory or Relapsed Malignancies

Baseline characteristics by cohort

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=6 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=21 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	Total n=39 Participants Total of all reporting groups
Age, Continuous	56.5 years STANDARD_DEVIATION 5.7 • n=5 Participants	68.3 years STANDARD_DEVIATION 9.4 • n=7 Participants	61.0 years STANDARD_DEVIATION 10.4 • n=5 Participants	63.2 years STANDARD_DEVIATION 10.0 • n=4 Participants	62.6 years STANDARD_DEVIATION 9.7 • n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants	17 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants	22 Participants n=21 Participants
Race/Ethnicity, Customized White	4 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	18 participants n=4 Participants	29 participants n=21 Participants
Race/Ethnicity, Customized Black	2 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants	10 participants n=21 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	21 participants n=4 Participants	39 participants n=21 Participants
Body Weight in kilograms (kg)	96.8 kg n=5 Participants	73.9 kg n=7 Participants	81.9 kg n=5 Participants	81.3 kg n=4 Participants	81.3 kg n=21 Participants
Time since initial diagnosis (years)	3.7 Years n=5 Participants	2.7 Years n=7 Participants	5.6 Years n=5 Participants	4.1 Years n=4 Participants	3.8 Years n=21 Participants
Type of Malignancy Prostate Cancer	0 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	5 participants n=4 Participants	8 participants n=21 Participants
Type of Malignancy Melanoma	0 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	8 participants n=4 Participants	10 participants n=21 Participants
Type of Malignancy Non-small cell lung cancer	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	6 participants n=21 Participants
Type of Malignancy Renal cell cancer	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Type of Malignancy Colorectal cancer	5 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	5 participants n=4 Participants	14 participants n=21 Participants
Stage of Malignancy at Screening Diagnosis Stage I	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
Stage of Malignancy at Screening Diagnosis Stage II	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
Stage of Malignancy at Screening Diagnosis Stage III	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Stage of Malignancy at Screening Diagnosis Stage IV	5 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	21 participants n=4 Participants	38 participants n=21 Participants

PRIMARY outcome

Timeframe: Day 1 to 70 days post last dose of study drug; 28 days past study discontinuation

Population: Safety Population: All participants who received at least 1 dose or any partial dose of nivolumab were analyzed.

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Severe=All Grade 3 or 4 events. Death=during the study and up to 28 days past study discontinuation. AEs graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. irAEs=unknown etiology, associated with study drug and consistent with an immune phenomenon. DLT: ≥Gr 3 AE(s) or lab abnormality without alternative explanation other than drug.

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=6 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=21 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population Severe AE	5 participants	5 participants	4 participants	18 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population SAE	3 participants	5 participants	4 participants	9 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population SAE through 28 days post study discontinuation	3 participants	5 participants	4 participants	11 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population Drug-Related AE	5 participants	5 participants	6 participants	19 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population Death	1 participants	4 participants	1 participants	6 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population Discontinuation of Study Drug due to AE	0 participants	0 participants	0 participants	2 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population irAE	1 participants	3 participants	2 participants	9 participants
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population Dose-Limiting Toxicity AE	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 1 to Day 85

Population: All participants who received at least 1 dose or any partial dose of nivolumab and had adequate PK profiles were included in the summary statistics.

Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated enzyme-linked immunosorbent assay (ELISA) method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The pharmacokinetic (PK) parameter of Cmax was measured in micrograms per milliliter (µg/mL).

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=5 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=21 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Geometric Mean Maximum Serum Concentration (Cmax) Observed Post-Single Dose	6.7 µg/mL Geometric Coefficient of Variation 21.6	16.0 µg/mL Geometric Coefficient of Variation 32.1	60.0 µg/mL Geometric Coefficient of Variation 27.6	196.3 µg/mL Geometric Coefficient of Variation 19.5

PRIMARY outcome

Timeframe: Day 1 to Day 85

Population: All participants who received at least 1 dose or any partial dose of nivolumab and had adequate PK profiles were included in the summary statistics.

Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of Tmax was measured in hours (h).

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=5 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=21 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Median Time at Which the Maximum Serum Concentration Occurred (Tmax) Post-Single Dose	3.0 h Interval 1.0 to 6.8	1.9 h Interval 1.0 to 7.0	3.1 h Interval 1.0 to 5.0	1.6 h Interval 0.9 to 7.0

PRIMARY outcome

Timeframe: Day 1 to Day 85

Population: All participants who received at least 1 dose or any partial dose of nivolumab and had adequate PK profiles were included in the summary statistics.

AUC(0-T): Area under the concentration-time curve from the time of dosing to the time of the last observation. AUC(INF): Area under the curve from the time of dosing extrapolated to infinity. Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameters of AUC(0-T) and AUC (INF) were measured in micrograms*hours per milliliter (µg*h/mL).

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=5 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=21 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Geometric Mean Area Under the Curve (AUC) From Time of Dosing to Time of Last Observation (0-T) and Extrapolated to Infinity (INF) Observed Post-Single Dose AUC (0-T); n=6, 6, 5, 21	970 µg*h/mL Geometric Coefficient of Variation 47	3244 µg*h/mL Geometric Coefficient of Variation 62	13909 µg*h/mL Geometric Coefficient of Variation 44	55324 µg*h/mL Geometric Coefficient of Variation 39
Geometric Mean Area Under the Curve (AUC) From Time of Dosing to Time of Last Observation (0-T) and Extrapolated to Infinity (INF) Observed Post-Single Dose AUC (INF); n=3, 4, 5, 19	2343 µg*h/mL Geometric Coefficient of Variation 16	6014 µg*h/mL Geometric Coefficient of Variation 30	15813 µg*h/mL Geometric Coefficient of Variation 44	76541 µg*h/mL Geometric Coefficient of Variation 27

PRIMARY outcome

Timeframe: Day 1 to Day 85

Population: All participants who received at least 1 dose or any partial dose of nivolumab and had adequate PK profiles were included in the summary statistics.

Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of T-HALF was measured in days.

Outcome measures

Measure	0.3 mg/kg Nivolumab n=3 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=4 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=5 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=19 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Mean Elimination Half-life (T-HALF) Post-Single Dose	18.9 days Standard Deviation 7.05	17.0 days Standard Deviation 2.36	17.0 days Standard Deviation 4.70	24.8 days Standard Deviation 7.22

PRIMARY outcome

Timeframe: Day 1 to Day 85

Population: All participants who received at least 1 dose or any partial dose of nivolumab and had adequate PK profiles were included in the summary statistics.

Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of CLT was measured in milliliters per hour per kilogram body weight (mL/h/kg).

Outcome measures

Measure	0.3 mg/kg Nivolumab n=3 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=4 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=5 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=19 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Geometric Mean Total Body Clearance of Drug From Serum (CLT) Post-Single Dose	0.13 mL/h/kg Geometric Coefficient of Variation 16.93	0.17 mL/h/kg Geometric Coefficient of Variation 29.80	0.19 mL/h/kg Geometric Coefficient of Variation 42.66	0.13 mL/h/kg Geometric Coefficient of Variation 28.42

PRIMARY outcome

Timeframe: Day 1 to Day 85

Population: All participants who received at least 1 dose or any partial dose of nivolumab and had adequate PK profiles were included in the summary statistics.

Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of Vz was measured in milliliters per kilogram of body weight (mL/kg).

Outcome measures

Measure	0.3 mg/kg Nivolumab n=3 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=4 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=5 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=19 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Mean Volume of Distribution (Vz) Post-Single Dose	82.8 mL/kg Standard Deviation 27.19	99.6 mL/kg Standard Deviation 23.04	112.7 mL/kg Standard Deviation 39.50	109.4 mL/kg Standard Deviation 26.70

PRIMARY outcome

Timeframe: Day 1 up to 2 Years.

Population: Safety Population: All participants who received at least 1 dose or any partial dose of nivolumab were analyzed. Tumor Evaluable Population: all participants who received complete dose(s) of nivolumab and had completed a major tumor assessment (a baseline and at least 1 post-baseline tumor assessment for either target and/or non-target assessments.

The Best Overall Response Rate (BORR) was defined as the number of participants who had a confirmed complete response (CR) or partial response (PR) during the study divided by the total number of participants evaluated. Response was based on tumor assessment for both target and non-target lesions using: Clinical examination; Chest X-ray; Computed Tomography and Magnetic Resonance Imaging; Bone scan; Ultrasound. Per National Cancer Institute Response Evaluation Criteria in Solid Tumors (RECIST) v1.0, best overall response (BOR) for tumors was confirmed CR or PR. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter. Confidence intervals (CIs) were computed using the Clopper and Pearson method.

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=6 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=21 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Percent of Participants With Best Overall Response Rate in Safety Population and in Tumor Evaluable Population Safety Population (n=6,6,6,21)	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 45.9	16.7 percentage of participants Interval 0.4 to 64.1	9.5 percentage of participants Interval 1.2 to 30.4
Percent of Participants With Best Overall Response Rate in Safety Population and in Tumor Evaluable Population Tumor Evaluable Population (n=6,5,6,20)	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 52.2	16.7 percentage of participants Interval 0.4 to 64.1	10.0 percentage of participants Interval 1.2 to 31.7

PRIMARY outcome

Timeframe: Day 1 to Day 85

Population: The PSA evaluable population was analyzed and included all HRPC participants who received complete dose(s) of nivolumab and had a baseline PSA assessment and at least one post baseline PSA assessment. A PSA evaluable participant could not have any major inclusion/exclusion violation, dosing violation, or protocol conduct violation.

The PSA response rate was defined as the number of participants who had at least a 50% decrease of the PSA value from the PSA reference value divided by the total number of participants evaluated (percent of participants). PSA reference value was the PSA concentration measured immediately prior to dosing on Day 1. PSA response was assessed using the Recommendations from the National Cancer Institute Prostate-Specific Antigen Working Group. A PSA response had to be confirmed at least 4 weeks after first response. 95% exact CIs were computed using the Clopper and Pearson method.

Outcome measures

Measure	0.3 mg/kg Nivolumab 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=1 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=2 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=5 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Percent of Participants With Prostate-Specific Antigen (PSA) Response After the First Dose by Day 85 In Participants With Hormone-Refractory Prostate Adenocarcinoma (HRPC)	—	0 percentage of participants Interval 0.0 to 97.5	0 percentage of participants Interval 0.0 to 84.2	0 percentage of participants Interval 0.0 to 52.2

SECONDARY outcome

Timeframe: Day 1 to Day 85

Population: Safety Population: All participants who received at least 1 dose or any partial dose of nivolumab were analyzed.

Measurable and non-measurable disease/target lesions were evaluated according to National Cancer Institute standardized RECIST.Complete Response (CR)=disappearance of all target and non-target lesions and no new lesions; Partial Response=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter; Stable disease (SD)=neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since treatment; PD=at least a 20% increase in the sum of the longest diameter recorded since screening, or the appearance of one or more new lesions. BOR was recorded between the first tumor assessment and last tumor assessment. CR and PR had to be confirmed by repeat assessment no less than 4 weeks after the criteria were first met. SD assessment must have met the criteria at least once at or after Week 12.

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=6 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=21 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Number of Participants With Best Overall Response (BOR) by Category in Safety Population Complete Response	0 participants	0 participants	0 participants	0 participants
Number of Participants With Best Overall Response (BOR) by Category in Safety Population Partial Response	0 participants	0 participants	1 participants	2 participants
Number of Participants With Best Overall Response (BOR) by Category in Safety Population Stable Disease	1 participants	1 participants	2 participants	6 participants
Number of Participants With Best Overall Response (BOR) by Category in Safety Population Progressive Disease	5 participants	4 participants	3 participants	12 participants
Number of Participants With Best Overall Response (BOR) by Category in Safety Population Unknown	0 participants	0 participants	0 participants	1 participants
Number of Participants With Best Overall Response (BOR) by Category in Safety Population Missing	0 participants	1 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 to 2 Years

Population: Safety Population was analyzed: All participants who received at least 1 dose or any partial dose of nivolumab.

Disease control rate was defined as number of participants whose Best Overall Response (BOR) was complete response (CR), partial response (PR), or stable disease (SD) divided by the total number of participants. Major durable disease control rate was defined as the total number of participants whose BOR was CR, PR, or SD ≥24 weeks, divided by the total number of participants. Per RECIST v 1.0, BOR for tumors was confirmed CR or PR. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter since treatment; SD=neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for PD. PD=at least a 20% increase in the sum of the longest diameter recorded since screening, or the appearance of one or more new lesions. 95% CIs were computed using the Clopper and Pearson method.

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=6 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=21 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Percentage of Participants With Disease Control and Major Durable Disease Control Disease Control Rate	16.7 percentage of participants Interval 0.4 to 64.1	16.7 percentage of participants Interval 0.4 to 64.1	50.0 percentage of participants Interval 11.8 to 88.2	38.1 percentage of participants Interval 18.1 to 61.6
Percentage of Participants With Disease Control and Major Durable Disease Control Major Durable Disease Control Rate ≥24 weeks	0 percentage of participants Interval 0.0 to 45.9	16.7 percentage of participants Interval 0.4 to 64.1	33.3 percentage of participants Interval 4.3 to 77.7	4.8 percentage of participants Interval 0.1 to 23.8

SECONDARY outcome

Timeframe: Day 1 to 2 Years

Population: All participants who received at least 1 dose or any partial dose of nivolumab and were tumor responders were analyze.

Time to tumor response: from the date of first dose to the first date of tumor response (CR or PR confirmed at least 4 weeks later); for nonresponders, it was censored at the date of the maximum tumor assessment time in the dose cohort by the end of study. Duration of tumor response was calculated from the first date of response of CR or PR to the date of the first PD or the date of death if a participant died due to disease progression (whichever occurred first). Duration of response was censored at the last tumor assessment date by the end of study if a responder did not have PD or death. Nonresponders had the duration of response as an event of 0 days.

Outcome measures

Measure	0.3 mg/kg Nivolumab 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=1 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=2 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Median Time to Tumor Response and Duration of Tumor Response Time to Tumor Response	—	—	57 days insufficient number of participants to calculate CI	386 days Interval 85.0 to 687.0
Median Time to Tumor Response and Duration of Tumor Response Duration of Tumor Response	—	—	796 days insufficient number of participants to calculate CI	327 days Interval 92.0 to 562.0

SECONDARY outcome

Timeframe: Day 1 to 2 Years

Population: All participants who received at least 1 dose or any partial dose of nivolumab were analyzed.

Time to tumor progression (TTP) was measured in days from date of the first dose to the date of the first PD or the date of death if due to PD. For those who died without PD it was censored at the date of death. TTP was censored at the last tumor assessment by the end of study if a participant did not have PD or death. Tumor progression free survival (PFS) was measured in days from the date of first dose to the date of the first disease progression or to the date of death. PFS was censored at the last tumor assessment date by the end of study if a participant did not have PD or death.

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=6 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=21 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Time to Tumor Progression and Tumor Progression Free Survival Time to Tumor Progression	56 days Interval 51.0 to 57.0	57.5 days Interval 57.0 to 59.0	86 days Interval 57.0 to 193.0	57 days Interval 53.0 to 85.0
Time to Tumor Progression and Tumor Progression Free Survival Tumor Progression Free Survival	56 days Interval 51.0 to 57.0	57.5 days Interval 57.0 to 59.0	86 days Interval 57.0 to 193.0	57 days Interval 53.0 to 85.0

SECONDARY outcome

Timeframe: Day 1 to 2 Years

Population: The PSA evaluable population include all participants in the study who received complete dose(s) of nivolumab and had a baseline PSA assessment and at least 1 post-baseline PSA assessment.

Time to PSA progression: first dose to first PSA progression. Missing date of progression was censored: if death during the study, time to progression was right-censored at last PSA assessment; if no progression from first dose and still alive at end of study, time to progression was right-censored at last PSA assessment by end of study; if no PSA progression and one has discontinued from the study (other than death or PSA progression), time to progression was right-censored at last PSA assessment. PSA progression free survival (PFS): first dose to first PSA progression or death, whichever comes first. Missing date of progression was censored: if one did not have PSA progression from first dose and was still alive at end of study, PSA PFS was right-censored at last PSA assessment; if one does not have any progression and discontinued from the study for reasons other than death or progression, PFS was right-censored at last assessment. CI computed using Brookmeyer and Crowley method.

Outcome measures

Measure	0.3 mg/kg Nivolumab 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=1 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=2 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=5 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Median Time to PSA Progression in Days and Median PSA Progression Free Survival in Days in PSA Evaluable Population Time to PSA Progression	—	29 days insufficient number of participants to calculate CI	58.5 days Interval 29.0 to 88.0	29 days Interval 22.0 to 57.0
Median Time to PSA Progression in Days and Median PSA Progression Free Survival in Days in PSA Evaluable Population PSA Progression Free Survival	—	29 days insufficient number of participants to calculate CI	58.5 days Interval 29.0 to 88.0	29 days Interval 22.0 to 57.0

SECONDARY outcome

Timeframe: Day 29, Day 57, Day 85

Population: The PSA evaluable population includes all participants in the study who received complete dose(s) of nivolumab and has a baseline PSA assessment and at least 1 post-baseline PSA assessment.

PSA relative velocity (PSA RV) was defined as = (d[PSA]/dt)/ [PSA], where [PSA] =concentration of PSA, and t= time, and in the limit reflects the instantaneous change in PSA levels as a fraction of total PSA level. Decreases in PSA RV may occur while measured [PSA] is still rising, and may indicate that continued therapy may lead to a treatment benefit, particularly in the setting of immunotherapy, where expansion of an effective immune response is likely to require weeks to mature. Baseline PSA RV was based on the velocity of last PSA measurement before the first infusion of study drug and the screening PSA measurement.

Outcome measures

Measure	0.3 mg/kg Nivolumab 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=1 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=2 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=5 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Mean Change From Baseline in PSA Relative Velocity at Days 29, 57, and 85 With Cycle 1 in PSA Evaluable Population Cycle 1 Day 29 (n=0, 1, 2, 5)	—	0.009 percentage of total PSA level Interval 0.009 to 0.009	-0.007 percentage of total PSA level Interval -0.017 to 0.003	-0.015 percentage of total PSA level Interval -0.04 to 0.002
Mean Change From Baseline in PSA Relative Velocity at Days 29, 57, and 85 With Cycle 1 in PSA Evaluable Population Cycle 1 Day 57 (n=0, 1, 2, 5)	—	0.003 percentage of total PSA level Interval 0.003 to 0.003	-0.009 percentage of total PSA level Interval -0.01 to -0.008	0.001 percentage of total PSA level Interval -0.036 to 0.018
Mean Change From Baseline in PSA Relative Velocity at Days 29, 57, and 85 With Cycle 1 in PSA Evaluable Population Cycle 1 Day 85 (n=0, 1, 2, 4)	—	0.007 percentage of total PSA level Interval 0.007 to 0.007	0.001 percentage of total PSA level Interval -0.003 to 0.004	-0.005 percentage of total PSA level Interval -0.044 to 0.017

SECONDARY outcome

Timeframe: Baseline, Day 2, Day 85, Day 113

Population: All participants who received at least 1 dose or any partial dose of nivolumab and had available ECG at baseline and on the specified post treatment study day were analyzed.

12-lead ECGs were performed at screening, baseline, Day 2 and at completion of the dose cycle (Day 85 in first dose cycle). In those participants undergoing re-treatment, ECG was repeated at the completion of the re-treatment. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. PR, QRS and QT interval were measured in milliseconds (msec).

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=6 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=21 Participants 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population PR at Day 2 (n=6,6,6,21)	7.3 msec Standard Deviation 6.15	-9.7 msec Standard Deviation 10.31	-1.7 msec Standard Deviation 9.75	-0.3 msec Standard Deviation 13.72
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population QRS at Day 2 (n=6,6,6,21)	5.0 msec Standard Deviation 6.90	-2.0 msec Standard Deviation 7.48	-8.7 msec Standard Deviation 19.83	-1.2 msec Standard Deviation 5.57
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population QT at Day 2 (n=6,6,6,21)	2.0 msec Standard Deviation 27.86	-15.7 msec Standard Deviation 22.89	-2.0 msec Standard Deviation 15.90	-10.1 msec Standard Deviation 20.76
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population PR at Day 57 (n=0,0,0,3)	NA msec Standard Deviation NA no participants with data on this day in this arm	NA msec Standard Deviation NA no participants with data on this day in this arm	NA msec Standard Deviation NA no participants with data on this day in this arm	-11.3 msec Standard Deviation 24.11
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population QRS at Day 57 (n=0,0,0,3)	NA msec Standard Deviation NA no participants with data on this day in this arm	NA msec Standard Deviation NA no participants with data on this day in this arm	NA msec Standard Deviation NA no participants with data on this day in this arm	1.3 msec Standard Deviation 5.03
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population QT at Day 57 (n=0,0,0,3)	NA msec Standard Deviation NA no participants with data on this day in this arm	NA msec Standard Deviation NA no participants with data on this day in this arm	NA msec Standard Deviation NA no participants with data on this day in this arm	5.3 msec Standard Deviation 33.61
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population PR at Day 85 (n=0,4,4,11)	NA msec Standard Deviation NA no participants with data on this day in this arm	-4.5 msec Standard Deviation 11.82	3.5 msec Standard Deviation 17.69	-1.1 msec Standard Deviation 17.44
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population QRS at Day 85 (n=0,4,4,11)	NA msec Standard Deviation NA no participants with data on this day in this arm	-6.0 msec Standard Deviation 9.09	-4.0 msec Standard Deviation 6.73	0.2 msec Standard Deviation 4.24
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population QT at Day 85 (n=0,4,4,11)	NA msec Standard Deviation NA no participants with data on this day in this arm	-6.0 msec Standard Deviation 27.90	-3.5 msec Standard Deviation 33.52	-0.2 msec Standard Deviation 26.40
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population PR at Day 113 (n=0,0,2,3)	NA msec Standard Deviation NA no participants with data on this day in this arm	NA msec Standard Deviation NA no participants with data on this day in this arm	11.0 msec Standard Deviation 24.04	3.3 msec Standard Deviation 4.62
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population QRS at Day 113 (n=0,0,2,3)	NA msec Standard Deviation NA no participants with data on this day in this arm	NA msec Standard Deviation NA no participants with data on this day in this arm	4.0 msec Standard Deviation 2.83	6.0 msec Standard Deviation 6.93
Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population QT at Day 113 (n=0,0,2,3)	NA msec Standard Deviation NA no participants with data on this day in this arm	NA msec Standard Deviation NA no participants with data on this day in this arm	4.0 msec Standard Deviation 50.91	6.0 msec Standard Deviation 28.00

SECONDARY outcome

Timeframe: Baseline, Day 1

Population: All participants who received at least 1 dose or any partial dose of nivolumab and had available blood pressure at baseline and post-infusion were analyzed.

Diastolic blood pressures (DBPs) measured in millimeters of mercury (mmHg) were obtained while the participant was seated. Post infusion DBPs are presented in the 0.3 mg cohort at: 21, 36, 51, 66, 82, 97, 112, 127, 157 minutes post infusion, and at 1, 2, 3, 4, 6, 8 hours post infusion. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. Mean DBP on Day 1 for first dose (cycle 1) are presented below.

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population Baseline (n=6)	80.3 mmHg Standard Deviation 18.16	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population Infusion (0 minutes) (n=5)	82.4 mmHg Standard Deviation 10.01	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 21 minutes post infusion (n=6)	87.0 mmHg Standard Deviation 10.28	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 36 minutes post infusion (n=6)	81.0 mmHg Standard Deviation 10.88	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 51 minutes post infusion (n=6)	79.8 mmHg Standard Deviation 9.20	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 66 minutes post infusion (n=6)	80.3 mmHg Standard Deviation 8.71	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 82 minutes post infusion (n=6)	81.7 mmHg Standard Deviation 8.69	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 97 minutes post infusion (n=6)	80.3 mmHg Standard Deviation 10.56	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 112 minutes post infusion (n=6)	78.7 mmHg Standard Deviation 8.14	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 127 minutes post infusion (n=6)	81.0 mmHg Standard Deviation 11.14	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 157 minutes post infusion (n=2)	72.5 mmHg Standard Deviation 6.36	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 1 hour post infusion (n=6)	80.5 mmHg Standard Deviation 8.96	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 2 hour post infusion (n=6)	82.2 mmHg Standard Deviation 11.02	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 3 hour post infusion (n=6)	74.5 mmHg Standard Deviation 6.35	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 4 hour post infusion (n=6)	73.8 mmHg Standard Deviation 6.08	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 6 hour post infusion (n=6)	78.2 mmHg Standard Deviation 10.44	—	—	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 8 hour post infusion (n=6)	76.2 mmHg Standard Deviation 5.67	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 1

Population: All participants who received at least 1 dose or any partial dose of nivolumab and had available blood pressure at baseline and post-infusion were analyzed.

Systolic blood pressures (SBPs) measured in millimeters of mercury (mmHg) were obtained while the participant was seated. Baseline, Infusion (0 minutes) and Post infusion SBPs are presented in the 0.3 mg cohort at: 21, 36, 51, 66, 82, 97, 112, 127, 157 minutes post infusion, and at 1, 2, 3, 4, 6, 8 hours post infusion. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. Mean SBP on Day 1 for first dose (cycle 1) are presented below.

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population Baseline (n=6)	141.8 mmHg Standard Deviation 15.03	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population Infusion (0 minutes) (n=5)	144.2 mmHg Standard Deviation 17.05	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 21 minutes post infusion (n=6)	154.3 mmHg Standard Deviation 22.90	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 36 minutes post infusion (n=6)	140.3 mmHg Standard Deviation 14.71	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 51 minutes post infusion (n=6)	147.5 mmHg Standard Deviation 10.05	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 66 minutes post infusion (n=6)	141.0 mmHg Standard Deviation 15.44	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 82 minutes post infusion (n=6)	145.7 mmHg Standard Deviation 17.60	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 97 minutes post infusion (n=6)	141.8 mmHg Standard Deviation 16.29	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 112 minutes post infusion (n=6)	139.8 mmHg Standard Deviation 11.55	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 127 minutes post infusion (n=6)	140.3 mmHg Standard Deviation 20.47	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 157 minutes post infusion (n=2)	137.5 mmHg Standard Deviation 7.78	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 1 hour post infusion (n=6)	139.3 mmHg Standard Deviation 8.04	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 2 hour post infusion (n=6)	145.8 mmHg Standard Deviation 20.85	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 3 hour post infusion (n=6)	140.3 mmHg Standard Deviation 7.92	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 4 hour post infusion (n=6)	139.8 mmHg Standard Deviation 9.89	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 6 hour post infusion (n=6)	142.8 mmHg Standard Deviation 19.06	—	—	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population 8 hour post infusion (n=6)	145.5 mmHg Standard Deviation 12.77	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 1

Population: All participants who received at least 1 dose or any partial dose of nivolumab and had available blood pressure at baseline and post-infusion were analyzed.

Diastolic blood pressures (DBPs) measured in millimeters of mercury (mmHg) were obtained while the participant was seated. Baseline, Infusion (0 minutes) and Post infusion DBPs are presented in the 1 mg, 3 mg and 10 mg cohorts at: 15, 30, 45, 60, 75, and 90 minutes post infusion and at 1, 2, 3, 4, 6, 8 hours post infusion. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. Mean DBP on Day 1 for first dose (cycle 1) are presented below.

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=21 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population Baseline (n=6, 6, 21)	80.3 mmHg Standard Deviation 11.62	72.2 mmHg Standard Deviation 10.72	74.4 mmHg Standard Deviation 12.19	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population Infusion (0 minutes) (n=6, 5, 19)	79.2 mmHg Standard Deviation 11.72	73.6 mmHg Standard Deviation 10.01	74.2 mmHg Standard Deviation 11.31	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population 15 minutes post infusion (n=6,6,21)	74.5 mmHg Standard Deviation 11.41	69.5 mmHg Standard Deviation 10.41	72.3 mmHg Standard Deviation 11.87	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population 30 minutes post infusion (n=6,6,21)	78.8 mmHg Standard Deviation 11.0	70.7 mmHg Standard Deviation 10.29	71.1 mmHg Standard Deviation 10.40	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population 45 minutes post infusion (n=6,6,21)	75.7 mmHg Standard Deviation 10.67	69.8 mmHg Standard Deviation 12.09	72.7 mmHg Standard Deviation 12.69	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population 60 minutes post infusion (n=6,6,21)	78.7 mmHg Standard Deviation 8.78	69.5 mmHg Standard Deviation 9.97	74.1 mmHg Standard Deviation 10.53	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population 75 minutes post infusion (n=5,3,12)	79.0 mmHg Standard Deviation 11.20	71.7 mmHg Standard Deviation 0.58	73.7 mmHg Standard Deviation 11.93	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population 90 minutes post infusion (n=4,4,14)	79.8 mmHg Standard Deviation 8.73	70.3 mmHg Standard Deviation 8.18	74.4 mmHg Standard Deviation 11.09	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population 1 hour post infusion (n= 6,5,21)	78.5 mmHg Standard Deviation 7.58	74.4 mmHg Standard Deviation 17.18	71.9 mmHg Standard Deviation 10.24	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population 2 hour post infusion (n= 6,6,21)	83.0 mmHg Standard Deviation 10.35	70.7 mmHg Standard Deviation 19.04	72.0 mmHg Standard Deviation 10.62	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population 3 hour post infusion (n= 6,5,19)	79.5 mmHg Standard Deviation 13.20	67.8 mmHg Standard Deviation 24.59	72.9 mmHg Standard Deviation 11.98	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population 4 hour post infusion (n= 6,6,21)	75.2 mmHg Standard Deviation 17.68	69.2 mmHg Standard Deviation 13.64	73.5 mmHg Standard Deviation 9.86	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population 6 hour post infusion (n= 6,6,21)	74.7 mmHg Standard Deviation 7.81	77.7 mmHg Standard Deviation 13.35	73.1 mmHg Standard Deviation 10.32	—
Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population 8 hour post infusion (n= 5,5,21)	83.8 mmHg Standard Deviation 8.04	76.4 mmHg Standard Deviation 15.29	74.7 mmHg Standard Deviation 8.33	—

SECONDARY outcome

Timeframe: Baseline, Day 1

Population: All participants who received at least 1 dose or any partial dose of nivolumab and had available blood pressure at baseline and post-infusion were analyzed.

Systolic blood pressures (SBPs) measured in millimeters of mercury (mmHg) were obtained while the participant was seated. Baseline, Infusion (0 minutes) and Post infusion SBPs are presented in the 1 mg, 3 mg and 10 mg cohorts at: 15, 30, 45, 60, 75, and 90 minutes post infusion and at 1, 2, 3, 4, 6, 8 hours post infusion. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. Mean SBPs on Day 1 for first dose (cycle 1) are presented below.

Outcome measures

Measure	0.3 mg/kg Nivolumab n=6 Participants 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 Participants 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=21 Participants 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population Baseline (n=6, 6, 21)	133.2 mmHg Standard Deviation 2.86	121.3 mmHg Standard Deviation 13.11	128.8 mmHg Standard Deviation 19.29	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population Infusion (0 minutes) (n=6, 5, 19)	138.8 mmHg Standard Deviation 10.65	116.4 mmHg Standard Deviation 8.56	129.5 mmHg Standard Deviation 17.38	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population 15 minutes post infusion (n=6,6,21)	136.7 mmHg Standard Deviation 12.03	117.3 mmHg Standard Deviation 8.64	125.5 mmHg Standard Deviation 16.54	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population 30 minutes post infusion (n=6,6,21)	139.2 mmHg Standard Deviation 6.71	119.8 mmHg Standard Deviation 10.82	124.0 mmHg Standard Deviation 14.00	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population 45 minutes post infusion (n=6,6,21)	141.2 mmHg Standard Deviation 12.19	111.5 mmHg Standard Deviation 5.79	123.5 mmHg Standard Deviation 14.38	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population 60 minutes post infusion (n=6,6,21)	142.3 mmHg Standard Deviation 3.78	115.0 mmHg Standard Deviation 5.69	124.8 mmHg Standard Deviation 14.39	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population 75 minutes post infusion (n=5,3,12)	134.0 mmHg Standard Deviation 8.69	119.3 mmHg Standard Deviation 10.21	126.2 mmHg Standard Deviation 18.01	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population 90 minutes post infusion (n=4,4,14)	134.0 mmHg Standard Deviation 7.62	119.0 mmHg Standard Deviation 8.76	126.1 mmHg Standard Deviation 14.24	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population 1 hour post infusion (n= 6,5,21)	141.2 mmHg Standard Deviation 5.74	120.6 mmHg Standard Deviation 15.69	121.2 mmHg Standard Deviation 16.72	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population 2 hour post infusion (n= 6,6,21)	131.3 mmHg Standard Deviation 9.91	119.7 mmHg Standard Deviation 11.04	123.4 mmHg Standard Deviation 14.76	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population 3 hour post infusion (n= 6,5,19)	133.5 mmHg Standard Deviation 9.79	122.2 mmHg Standard Deviation 12.24	125.4 mmHg Standard Deviation 15.29	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population 4 hour post infusion (n= 6,6,21)	133.0 mmHg Standard Deviation 9.94	128.5 mmHg Standard Deviation 19.61	125.9 mmHg Standard Deviation 13.20	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population 6 hour post infusion (n= 6,6,21)	137.0 mmHg Standard Deviation 11.63	130.0 mmHg Standard Deviation 14.21	124.6 mmHg Standard Deviation 15.77	—
Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population 8 hour post infusion (n= 5,5,21)	144.8 mmHg Standard Deviation 13.81	130.6 mmHg Standard Deviation 19.36	130.6 mmHg Standard Deviation 12.21	—

Adverse Events

0.3 mg/kg Nivolumab

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

1 mg/kg Nivolumab

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

3 mg/kg Nivolumab

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

10 mg/kg Nivolumab

Serious events: 11 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	0.3 mg/kg Nivolumab n=6 participants at risk 0.3 mg of nivolumab per kg of body weight was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 participants at risk 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=6 participants at risk 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=21 participants at risk 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Renal and urinary disorders Bladder obstruction	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Anorexia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Psychiatric disorders Confusional state	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Abdominal pain upper	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Central nervous system lesion	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Injury, poisoning and procedural complications Fracture	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Reproductive system and breast disorders Pelvic pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Renal and urinary disorders Renal failure	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Myoclonus	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Pneumonia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Blood and lymphatic system disorders Anaemia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Brain oedema	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Dehydration	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Ileus	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Sepsis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Renal and urinary disorders Ureteric obstruction	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Alanine aminotransferase increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Dizziness	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Spinal cord compression	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Ascites	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Colitis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Psychiatric disorders Mood altered	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Hepatobiliary disorders Acute hepatic failure	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Gastritis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Intestinal obstruction	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Psychiatric disorders Anxiety	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Aphasia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Renal and urinary disorders Nephrolithiasis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009

Other adverse events

Measure	0.3 mg/kg Nivolumab n=6 participants at risk 0.3 mg of nivolumab per kg of body weight was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	1 mg/kg Nivolumab n=6 participants at risk 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	3 mg/kg Nivolumab n=6 participants at risk 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.	10 mg/kg Nivolumab n=21 participants at risk 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Anorexia	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Injury, poisoning and procedural complications Back injury	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	42.9% 9/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood chloride decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood thyroid stimulating hormone increased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Carbon dioxide decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	28.6% 6/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Psychiatric disorders Confusional state	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Crystal urine present	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Electrocardiogram ST-T change	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Electrocardiogram abnormal	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Flatulence	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Glucose urine	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Hyperhidrosis	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Hypoaesthesia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hypocalcaemia	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	38.1% 8/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Vascular disorders Hypotension	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Infection	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Blood and lymphatic system disorders Leukopenia	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Non-cardiac chest pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Oral candidiasis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Injury, poisoning and procedural complications Procedural pain	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Sinus headache	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Infusion site oedema	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Urinary tract infection	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Lipase increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Vomiting	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	42.9% 9/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Melaena	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Weight decreased	83.3% 5/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	42.9% 9/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Abdominal pain upper	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood uric acid decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations CD4 lymphocytes decreased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	66.7% 14/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Monocyte count decreased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 7/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Crystal urine	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Psychiatric disorders Depression	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Diarrhoea haemorrhagic	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Dry mouth	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 7/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Dysphagia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Eosinophil count increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Erythema	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	23.8% 5/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Frequent bowel movements	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Groin pain	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hyperphosphataemia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations T-lymphocyte count decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Cardiac disorders Tachycardia	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Injury, poisoning and procedural complications Wound secretion	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Abdominal distension	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Cardiac disorders Atrial fibrillation	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations B-lymphocyte count increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Bacteria urine	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Bacteriuria	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	23.8% 5/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood creatinine increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood phosphorus increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood potassium decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood urine present	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Candidiasis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Chills	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Decreased appetite	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Renal and urinary disorders Dysuria	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Eosinophil count decreased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Eye disorders Eye pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Haematocrit decreased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Haemoglobin decreased	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Herpes zoster	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Blood and lymphatic system disorders Hypergammaglobulinaemia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Immune system disorders Hypersensitivity	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hypoalbuminaemia	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hypokalaemia	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hyponatraemia	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	23.8% 5/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Influenza like illness	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Psychiatric disorders Insomnia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Mean cell volume decreased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Monocyte count increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Blood and lymphatic system disorders Neutropenia	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Renal and urinary disorders Nocturia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Pruritus ani	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Rash pustular	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Rheumatoid factor	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Rheumatoid factor positive	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations White blood cell count increased	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations White blood cells urine	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Blood and lymphatic system disorders Anaemia	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	57.1% 12/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood bicarbonate decreased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	23.8% 5/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood bilirubin increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood lactate dehydrogenase increased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood magnesium decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations C-reactive protein increased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	38.1% 8/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Catheter site erythema	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Flank pain	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Folliculitis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Gingival pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Hepatobiliary disorders Hepatomegaly	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Injection site reaction	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Joint stiffness	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Mouth ulceration	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Cardiac disorders Palpitations	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Protein total decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Rash	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 7/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Reproductive system and breast disorders Scrotal swelling	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Skin exfoliation	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Stomatitis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Thyroxine decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Tremor	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Renal and urinary disorders Urinary incontinence	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Renal and urinary disorders Urinary retention	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Urine colour abnormal	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Weight increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Alanine aminotransferase increased	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Ataxia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations B-lymphocyte count decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood sodium decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	23.8% 5/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood urea decreased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations CD8 lymphocytes decreased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Carbon dioxide increased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Chest pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Dizziness	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	23.8% 5/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Dyspepsia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	28.6% 6/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Ear and labyrinth disorders Eustachian tube dysfunction	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Furuncle	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Headache	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 7/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Hepatobiliary disorders Hyperbilirubinaemia	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hyperkalaemia	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Neutrophil count increased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	23.8% 5/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Oedema	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Oedema peripheral	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Pain in extremity	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Pyrexia	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Sinus disorder	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Urinary sediment present	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 7/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Apraxia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Ascites	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Aspartate aminotransferase increased	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	28.6% 6/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Asthenia	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood alkaline phosphatase increased	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	61.9% 13/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Breath sounds abnormal	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations CD4 lymphocytes increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Cheilitis	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Colitis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	23.8% 5/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	23.8% 5/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Fatigue	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	83.3% 5/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	57.1% 12/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Renal and urinary disorders Haematuria	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hypermagnesaemia	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Vascular disorders Hypertension	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Blood and lymphatic system disorders Hypochromasia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Lethargy	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Mean cell haemoglobin concentration decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Blood and lymphatic system disorders Microcytosis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Nausea	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	52.4% 11/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Renal and urinary disorders Proteinuria	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	38.1% 8/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Red blood cell count decreased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Red blood cells urine	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Rheumatoid factor increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Sinusitis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Specific gravity urine increased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Upper respiratory tract infection	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations White blood cells urine positive	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood albumin decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood calcium decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood chloride increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood creatine phosphokinase increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood glucose increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 7/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood urea increased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood uric acid increased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Diarrhoea	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Dysgeusia	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	23.8% 5/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Facial wasting	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
General disorders Gait disturbance	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Gastritis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Haemorrhoids	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Hordeolum	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Vascular disorders Hot flush	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hyperglycaemia	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Blood and lymphatic system disorders Leukocytosis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Hepatobiliary disorders Liver disorder	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Blood and lymphatic system disorders Lymphopenia	66.7% 4/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	42.9% 9/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Mean cell haemoglobin decreased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Nervous system disorders Peripheral sensory neuropathy	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Platelet count increased	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	28.6% 6/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Pleural effusion	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Troponin increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Eye disorders Vision blurred	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Antinuclear antibody positive	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Psychiatric disorders Anxiety	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood phosphorus decreased	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood potassium increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Blood thyroid stimulating hormone decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	23.8% 5/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Bronchitis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Gastrointestinal disorders Constipation	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	47.6% 10/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Injury, poisoning and procedural complications Contusion	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Skin and subcutaneous tissue disorders Hypoaesthesia facial	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Interleukin level increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Hepatobiliary disorders Jaundice	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Lymphocyte count decreased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	50.0% 3/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	28.6% 6/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Muscle atrophy	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Injury, poisoning and procedural complications Muscle strain	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Musculoskeletal and connective tissue disorders Muscular weakness	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Postnasal drip	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	14.3% 3/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Infections and infestations Rhinitis	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Injury, poisoning and procedural complications Sunburn	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	9.5% 2/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations Thyroxine free increased	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	4.8% 1/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009
Investigations White blood cell count decreased	33.3% 2/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	16.7% 1/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	0.00% 0/6 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009	19.0% 4/21 • Day 1 through long-term follow-up until either progressive disease or 2 years elapsed. Study was initiated in 2006 and completed in 2009

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