Trial Outcomes & Findings for Comparison of Ipilimumab Manufactured by 2 Different Processes in Participants With Advanced Melanoma (NCT NCT00920907)

NCT ID: NCT00920907

Last Updated: 2014-06-20

Results Overview

Single-dose Pharmacokinetic (PK) parameters of ipilimumab were derived from serum concentration versus time data. Cmax was measured from first dose to end of the induction period (4 doses) as micrograms per milliliter (μg/mL). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox \[version 2.6.1\]).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 99 participants
• Primary outcome timeframe: Day 1 to Day 84
• Results posted on: 2014-06-20

Participant Flow

Study started August 3, 2009, ended October 31, 2012; Induction Phase (Weeks 1, 4, 7, 10), Maintenance Phase (participants without immune-related progressive disease (irPD) received ipilimumab every 12 weeks until disease progression, toxicity, pregnancy, death, withdrew consent, lost to follow up); Patients followed for 10 weeks post last dose.

99 participants enrolled; 75 participants randomized and treated. 24 participants not treated due to violations of inclusion or exclusion criteria.

Participant milestones

Measure	Ipilimumab (Process B) Intravenous (IV) solution of 10 milligrams (mg) ipilimumab per kilogram (kg) of body weight was given once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by the Lonza company using material from transfectoma cell line.	Ipilimumab (Process C) Intravenous (IV) solution of 10 milligrams (mg)ipilimumab per kilogram (kg) of body weight was given once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Induction Period STARTED	37	38
Induction Period COMPLETED	15	16
Induction Period NOT COMPLETED	22	22
Maintenance Period STARTED	15	15
Maintenance Period COMPLETED	3	2
Maintenance Period NOT COMPLETED	12	13

Reasons for withdrawal

Measure	Ipilimumab (Process B) Intravenous (IV) solution of 10 milligrams (mg) ipilimumab per kilogram (kg) of body weight was given once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by the Lonza company using material from transfectoma cell line.	Ipilimumab (Process C) Intravenous (IV) solution of 10 milligrams (mg)ipilimumab per kilogram (kg) of body weight was given once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Induction Period Adverse Event	0	2
Induction Period Death	1	1
Induction Period Disease Progression	12	11
Induction Period Study Drug Toxicity	8	6
Induction Period No longer meets study criteria	0	1
Induction Period Withdrawal by Subject	1	1
Maintenance Period Disease Progression	3	7
Maintenance Period Administrative (study closure)	7	2
Maintenance Period Study Drug Toxicity	0	2
Maintenance Period Death	1	1
Maintenance Period Withdrawal by Subject	1	0
Maintenance Period Adverse Event	0	1

Baseline Characteristics

Comparison of Ipilimumab Manufactured by 2 Different Processes in Participants With Advanced Melanoma

Baseline characteristics by cohort

Measure	Ipilimumab (Process B) n=37 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=38 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.	Total n=75 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants	24 Participants n=7 Participants	49 Participants n=5 Participants
Age, Categorical >=65 years	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Age, Continuous	57 years STANDARD_DEVIATION 14 • n=5 Participants	59 years STANDARD_DEVIATION 12 • n=7 Participants	58 years STANDARD_DEVIATION 13 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	24 Participants n=7 Participants	49 Participants n=5 Participants
Region of Enrollment United States	37 participants n=5 Participants	38 participants n=7 Participants	75 participants n=5 Participants
Body Weight	81.3 kg STANDARD_DEVIATION 13.4 • n=5 Participants	80.7 kg STANDARD_DEVIATION 13.3 • n=7 Participants	81.0 kg STANDARD_DEVIATION 13.3 • n=5 Participants
Eastern Cooperative Oncology Group (ECOG) ECOG=0	25 participants n=5 Participants	21 participants n=7 Participants	46 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) ECOG=1	12 participants n=5 Participants	17 participants n=7 Participants	29 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 84

Population: Pharmacokinetic (PK) evaluable Population: All participants who received at least one dose of drug and had adequate PK profiles.

Single-dose Pharmacokinetic (PK) parameters of ipilimumab were derived from serum concentration versus time data. Cmax was measured from first dose to end of the induction period (4 doses) as micrograms per milliliter (μg/mL). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox [version 2.6.1]).

Outcome measures

Measure	Ipilimumab (Process B) n=36 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=38 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Maximum Observed Serum Concentration (Cmax) of Ipilimumab Manufactured by Process C Relative to the Cmax of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population	252.68 μg/mL Geometric Coefficient of Variation 29	251.26 μg/mL Geometric Coefficient of Variation 24

PRIMARY outcome

Timeframe: Day 1 to Day 84

Population: PK evaluable Population: All participants who received at least one dose of drug and had adequate PK profiles.

The single-dose pharmacokinetic parameters of ipilimumab were derived from serum concentration versus time data. AUC(0-21d) was measured from first dose to end of the induction period as micrograms*hours per milliliter (μg*h/mL). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox [version 2.6.1]).

Outcome measures

Measure	Ipilimumab (Process B) n=33 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=36 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Area Under the Serum Concentration-time Curve (AUC) From Time Zero to Day 21, AUC(0-21d), of Ipilimumab Manufactured by Process C Relative to the AUC(0-21d) of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population	40374.47 μg*h/mL Geometric Coefficient of Variation 25	40085.9 μg*h/mL Geometric Coefficient of Variation 29

SECONDARY outcome

Timeframe: Day 1 to Day 84

Population: PK evaluable Population: All participants who received at least one dose of drug and had adequate PK profiles.

The single-dose Pharmacokinetic parameters of ipilimumab were derived from serum concentration versus time data. Tmax was measured from first dose to end of the induction period (4 doses) in hours (h). Samples were obtained at 0 h (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox [version 2.6.1]).

Outcome measures

Measure	Ipilimumab (Process B) n=36 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=38 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Time of Maximum Observed Serum Concentration (Tmax) of Ipilimumab Manufactured by Process C Relative to the Tmax of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population	2.00 h Interval 1.4 to 6.0	2.50 h Interval 1.4 to 6.0

SECONDARY outcome

Timeframe: Day 1 to Day 84

Population: PK evaluable Population: All participants who received at least one dose of drug and had adequate PK profiles.

The single-dose Pharmacokinetic parameters of ipilimumab were derived from serum concentration versus time data. T-HALF was measured from first dose to end of the induction period (4 doses) in day(s). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox [version 2.6.1]).

Outcome measures

Measure	Ipilimumab (Process B) n=33 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=36 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Terminal Elimination Half Life (T-HALF) of Ipilimumab Manufactured by Process C Relative to the T-HALF of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population	15.45 days Standard Deviation 6.93	15.23 days Standard Deviation 8.73

SECONDARY outcome

Timeframe: Day 1 to Day 84

Population: PK evaluable Population: All participants who received at least one dose of drug and had adequate PK profiles.

The single-dose Pharmacokinetic parameters of ipilimumab were derived from serum concentration versus time data. CLT was measured from first dose to end of the induction period (4 doses) in milliliters per hour (mL/h). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox [version 2.6.1]).

Outcome measures

Measure	Ipilimumab (Process B) n=33 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=36 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Clearance (CLT) of Ipilimumab Manufactured by Process C Relative to the CLT of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population	12.590 mL/h Geometric Coefficient of Variation 45	12.934 mL/h Geometric Coefficient of Variation 53

SECONDARY outcome

Timeframe: Day 1 to Day 84

Population: PK evaluable Population: All participants who received at least one dose of drug and had adequate PK profiles.

The single-dose Pharmacokinetic parameters of ipilimumab were derived from serum concentration versus time data. Vss was measured from first dose to end of the induction period (4 doses) in liter(s) (L). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox [version 2.6.1]).

Outcome measures

Measure	Ipilimumab (Process B) n=33 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=36 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Volume of Distribution at Steady State (Vss) of Ipilimumab Manufactured by Process C Relative to the Vss of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population	6.06 L Geometric Coefficient of Variation 21	5.96 L Geometric Coefficient of Variation 32

SECONDARY outcome

Timeframe: Day 1 to last patient, last visit, approximately 3 years

Population: All participants randomized to a treatment arm who received at least 1 dose of ipilimumab as randomized with measurable disease at baseline, at least one baseline assessment and one on-treatment tumor assessment, no resection of index lesions.

Overall Response (OR) was determined as the combination of assessments of index and non-index lesions using mWHO criteria which were: Complete Response=complete disappearance of all lesions; Partial Response=decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions, in the absence of Complete Response; Stable Disease=does not meet criteria for complete or partial response, in the absence of progressive disease, or a decrease or tumor stabilization of one or more non-index lesions; Progressive Disease (Progression)=at least 25% increase in the sum of the products of all index lesions (taking as reference the smallest sum recorded at or following baseline) and/or the appearance of any new lesion(s), or progression of non-index lesion(s). OR was measured across the entire study from Day 1 to the last patient, last visit (2009 to 2012)

Outcome measures

Measure	Ipilimumab (Process B) n=36 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=37 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Best Overall Tumor Response Per Investigator Based on Modified World Health Organization (mWHO) Criteria - All Randomized Participants Complete Response mWHO	0 participants	1 participants
Best Overall Tumor Response Per Investigator Based on Modified World Health Organization (mWHO) Criteria - All Randomized Participants Partial Response mWHO	4 participants	10 participants
Best Overall Tumor Response Per Investigator Based on Modified World Health Organization (mWHO) Criteria - All Randomized Participants Stable Disease mWHO	11 participants	7 participants
Best Overall Tumor Response Per Investigator Based on Modified World Health Organization (mWHO) Criteria - All Randomized Participants Progression mWHO	14 participants	17 participants
Best Overall Tumor Response Per Investigator Based on Modified World Health Organization (mWHO) Criteria - All Randomized Participants Unable to determine mWHO	7 participants	2 participants

SECONDARY outcome

Timeframe: Day 1 to last patient, last visit, approximately 3 years

Population: All participants randomized to a treatment arm who received at least 1 dose of ipilimumab as randomized with measurable disease at baseline, at least one baseline assessment and one on-treatment tumor assessment, no resection of index lesions, and for irRC, no resection of new lesions.

ir RC=modifications of mWHO criteria reflecting clinical experience with ipilimumab in over 20 completed and/or ongoing clinical studies. irRC were designed to capture clinical activity of ipilimumab immunotherapy that may not be adequately addressed by the mWHO criteria. irComplete Response (irCR): Complete disappearance of all index and non-index lesions. irPartial Response (irPR): Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index and all new measurable lesions in the absence of irCR, non-index lesions not considered. irStable Disease (irSD): Does not meet criteria for irCR or irPR, in the absence of progressive disease (irPD). irProgressive Disease (irPD): At least 25% increase in Tumor Burden when compared to sum of the products of diameters of lesions at nadir.

Outcome measures

Measure	Ipilimumab (Process B) n=33 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=34 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Best Overall Tumor Response Per Investigator Based on Immune-related (ir) Response Criteria (RC) - All Randomized Participants ir Complete Response	0 participants	1 participants
Best Overall Tumor Response Per Investigator Based on Immune-related (ir) Response Criteria (RC) - All Randomized Participants ir Partial Response	2 participants	9 participants
Best Overall Tumor Response Per Investigator Based on Immune-related (ir) Response Criteria (RC) - All Randomized Participants ir Stable Disease	11 participants	8 participants
Best Overall Tumor Response Per Investigator Based on Immune-related (ir) Response Criteria (RC) - All Randomized Participants ir Progression	14 participants	14 participants
Best Overall Tumor Response Per Investigator Based on Immune-related (ir) Response Criteria (RC) - All Randomized Participants Unable to determine	6 participants	2 participants

SECONDARY outcome

Timeframe: Week 1 (first dose) to last patient, last visit, approximately 3 years

Population: All participants who received at least one dose of ipilimumab.

Overall survival (OS) was defined as the time between the first dose of study treatment and death and was analyzed using Kaplan-Meier methods, with participants who had not died censored at the last date known to be alive. Overall survival was measured in months.

Outcome measures

Measure	Ipilimumab (Process B) n=37 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=38 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Median Overall Survival Following First Ipilimumab Dose - All Treated Participants	20.58 months Interval 8.55 to survival plateau close to 50%, therefore upper limit was not calculable	24.79 months Interval 21.04 to 36.57

SECONDARY outcome

Timeframe: Day 0 (prior to first dose) to Day 84

Population: All participants in the Pharmacodynamic data set with: (1) a baseline ALC evaluation; and (2) at least 1 post-baseline ALC evaluation (after the date of first dose).

Absolute lymphocyte counts (ALC) were obtained throughout the study as part of the hematology panel. Results collected from 28 days prior to the first infusion of ipilimumab through the end of the Induction-Dosing Period were included in the analyses of ALC. Mean ALC was estimated via an extended linear model, with linear splines and a spatial exponential within-patient correlation structure. Lymphocytes were measured as 1000 cells per micro liter (c/µL).

Outcome measures

Measure	Ipilimumab (Process B) n=37 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=38 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Model Estimates of Mean Absolute Lymphocyte Count at Each Nominal Ipilimumab Induction Dose and at End of the Induction Dosing Period 0 days since first dose	1.26 1000 c/µL Interval 0.99 to 1.53	1.18 1000 c/µL Interval 0.92 to 1.45
Model Estimates of Mean Absolute Lymphocyte Count at Each Nominal Ipilimumab Induction Dose and at End of the Induction Dosing Period 21 days since first dose	1.67 1000 c/µL Interval 1.4 to 1.94	1.74 1000 c/µL Interval 1.47 to 2.0
Model Estimates of Mean Absolute Lymphocyte Count at Each Nominal Ipilimumab Induction Dose and at End of the Induction Dosing Period 42 days since first dose	1.79 1000 c/µL Interval 1.51 to 2.07	1.86 1000 c/µL Interval 1.58 to 2.13
Model Estimates of Mean Absolute Lymphocyte Count at Each Nominal Ipilimumab Induction Dose and at End of the Induction Dosing Period 63 days since first dose	2.07 1000 c/µL Interval 1.79 to 2.36	1.94 1000 c/µL Interval 1.66 to 2.22
Model Estimates of Mean Absolute Lymphocyte Count at Each Nominal Ipilimumab Induction Dose and at End of the Induction Dosing Period 84 days since first dose	1.89 1000 c/µL Interval 1.52 to 2.27	2.01 1000 c/µL Interval 1.62 to 2.39

SECONDARY outcome

Timeframe: Day 1 to last patient, last visit, approximately 3 years

Population: All participants who received at least 1 dose of ipilimumab.

Adverse events (AEs) and Serious AEs (SAEs) were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events version 3.0. Medical Dictionary for Regulatory Activities (MedDRA) version 15.1 was used. Note there is a difference in number of participants with an SAE in this outcome measure and the number listed in the Adverse Events Section of this document. This is because the SAEs reported in the xml upload of the Adverse Events section includes additional participants who reported SAEs after the clinical study report database was closed.

Outcome measures

Measure	Ipilimumab (Process B) n=37 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=38 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation Participants with at least 1 AE	37 participants	38 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation Participants with at least 1 treatment related AE	33 participants	36 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation Participants with at least 1 SAE	22 participants	24 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation Participants with at least 1 treatment related SAE	10 participants	13 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation AE leading to discontinuation	14 participants	12 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation Participants who died	17 participants	20 participants

SECONDARY outcome

Timeframe: Prior to start of drug Week 1 to Week 24 on treatment or end of treatment

Population: Participants who received study drug and had HAHA data prior to infusion in Week 1 and while on treatment.

Electrochemiluminescent (ECL) Immunoassay was used to detect human anti-human ipilimumab antibodies (HAHA) in serum. Blood samples were collected prior to the start of each ipilimumab infusion at Weeks 1, 4, 7, 10, 24, and at end of treatment. Those participants who were positive HAHA on treatment were then tested for presence of neutralizing antibodies.

Outcome measures

Measure	Ipilimumab (Process B) n=34 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=36 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Number of Participants Who Developed Antibodies and Neutralizing Antibodies Positive HAHA on treatment	0 participants	2 participants
Number of Participants Who Developed Antibodies and Neutralizing Antibodies Neutralizing antibodies present	0 participants	0 participants

SECONDARY outcome

Timeframe: Screening to data cut off for July 2010, approximately 36 Weeks

Population: All participants who received at least 1 dose of ipilimumab and had available data at baseline and the specific timepoint.

Systolic and Diastolic blood pressure were measured in millimeters of mercury (mmHg) and were obtained after the participant had been seated for 5 minutes. Vital sign measurements were collected at Screening (baseline), Weeks 1, 4, 7, 10, 12, 24 and every 12 weeks thereafter in the Maintenance Phase, and at the End of Treatment visit. The change from baseline in blood pressure one hour post end of infusion at the end of induction Period, Week 36 of Maintenance Period, and end of treatment, up to data cutoff for July 2010 are presented below.

Outcome measures

Measure	Ipilimumab (Process B) n=10 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=12 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants up to Data Cutoff Diastolic at End of Induction (N=10, 12)	-1.6 mmHg Standard Deviation 10.1	-1.4 mmHg Standard Deviation 9.7
Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants up to Data Cutoff Diastolic at Week 36 of Maintenance (N=7, 7)	-7.0 mmHg Standard Deviation 14.1	-5.6 mmHg Standard Deviation 6.8
Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants up to Data Cutoff Diastolic at End of Treatment (N=6,7)	7.5 mmHg Standard Deviation 7.1	2.3 mmHg Standard Deviation 12.4
Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants up to Data Cutoff Systolic at End of Induction (N=10, 12)	-4.1 mmHg Standard Deviation 19.6	-8.6 mmHg Standard Deviation 21.0
Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants up to Data Cutoff Systolic at Week 36 of Maintenance (N=7, 7)	-5.7 mmHg Standard Deviation 31.5	-8.3 mmHg Standard Deviation 18.3
Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants up to Data Cutoff Systolic at End of Treatment (N=6,7)	11.5 mmHg Standard Deviation 13.3	-2.1 mmHg Standard Deviation 14.7

SECONDARY outcome

Timeframe: Screening to data cut off for July 2010, approximately 36 Weeks

Population: All participants who received at least 1 dose of ipilimumab and had available data at baseline and the specific timepoint.

Pulse Rate was measured in beats per minute (bpm) and was obtained after the participant had been seated for 5 minutes. Vital sign measurements were collected at Screening (baseline), Weeks 1, 4, 7, 10, 12, 24 and every 12 weeks thereafter in the Maintenance Phase, and at the End of Treatment visit. The change from baseline in blood pressure one hour post end of infusion at the end of induction Period, Week 36 of Maintenance Period, and end of treatment, up to data cutoff for July 2010 are presented below.

Outcome measures

Measure	Ipilimumab (Process B) n=10 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=24 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Mean Change From Baseline in Sitting Pulse Rate - All Treated Participants up to Data Cutoff Pulse Rate at End of Induction (N=10, 24)	-4.3 bpm Standard Deviation 11.1	-3.3 bpm Standard Deviation 11.1
Mean Change From Baseline in Sitting Pulse Rate - All Treated Participants up to Data Cutoff Pulse Rate at Week 36 (N=7,7))	-7.7 bpm Standard Deviation 15.3	-7.1 bpm Standard Deviation 8.8
Mean Change From Baseline in Sitting Pulse Rate - All Treated Participants up to Data Cutoff Pulse Rate at end of treatment (N=6,7)	25.5 bpm Standard Deviation 15.8	12.3 bpm Standard Deviation 10.5

SECONDARY outcome

Timeframe: Screening to data cut off for July 2010, approximately 36 Weeks

Population: All participants who received at least 1 dose of ipilimumab and had available data at baseline and post baseline.

Common Terminology Criteria (CTC), Version 3 used to assess parameters. Lower limit of normal (LLN); grams per deciliter (g/dL); Grade (GR); cells per microliter (c/µL). Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Absolute neutrophil (ANC) and ANC plus bands: Gr 1:<LLN to 1.5*10^3 c/µL, Gr 2:<1.5 to 1.0*10^3 c/µL, Gr 3:<1.0 to 0.5*10^3 c/µL, Gr 4:<0.5*10^3 c/µL. Platelet count Gr 1:LLN to 75.0*10^9 c/L, Gr 2:<75.0 to 50.0*10^9 c/L, Gr 3:<50.0 to 25.0*10^9 c/L, Gr 4:<25.0 to 10^9 c/L. Lymphocytes Gr 1: <1.5 to 0.8 *10^3 c/µL, Gr 2 <0.8 to 0.5 *10^3 c/µL, Gr 3: <0.5 to 0.2 *10^3 c/µL, Gr 4: <0.2*10^3 c/µL. Leukocytes Gr 1:<LLN to 3.0 *10^3 c/µL, Gr 2; <3.0 to 2.0 *10^3 c/µL, Gr 3: <2.0 to 1.0 *10^3 c/µL, Gr 4: <1.0 *10^3 c/µL. Baseline is screening or Day 1, prior to dosing.

Outcome measures

Measure	Ipilimumab (Process B) n=37 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=38 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Hematology Laboratory Safety Tests - All Treated Participants Hemoglobin (N=37, 38)	2 participants	3 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Hematology Laboratory Safety Tests - All Treated Participants Lymphocytes (N=37, 38)	3 participants	3 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Hematology Laboratory Safety Tests - All Treated Participants Neutrophils, Absolute (N=31, 36)	0 participants	2 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Hematology Laboratory Safety Tests - All Treated Participants Neutrophils + bands, Absolute (N=31, 36)	0 participants	1 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Hematology Laboratory Safety Tests - All Treated Participants Platelet Count (N=37, 38)	0 participants	1 participants

SECONDARY outcome

Timeframe: Screening to data cut off for July 2010, approximately 36 Weeks

Population: All participants who received at least 1 dose of ipilimumab and had available data at baseline and post baseline.

Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP); upper limits of normal (ULN). ALT Gr 1:>1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. AST Gr 1: >1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Total bilirubin Gr 1: >1.0 to 1.5*ULN; Gr 2: >1.5 to 3.0*ULN; Gr 3: >3.0 to 10..0*ULN; Gr 4: >10.0.0*ULN. ALP (U/L) Gr1:>1.0 to 2.5*ULN, Gr2:>2.5 to 5.0*ULN, Gr3:>5.0 to 20.0*ULN, Gr4:>20.0*ULN. Albumin (low) Gr 1:<LLN to 3 g/dL; Gr 2: <3.0 - 2.0 g/L; Gr 3: < 2 g/dL. Creatinine Gr 1: >1 - 1.5*ULN; Gr 2: >1.5 - 3.0*ULN; Gr 3: >3.0- 6.0*ULN; Gr 4: >6.0*ULN. Lipase (U/L) Gr 1: 1.0 to 1.5*ULN; Gr 2: >1.5 to 2.0*ULN; Gr 3: 2.0 to 5; Gr 4: >5*ULN. Amylase (U/L) Gr 1: >ULN to 1.5*ULN; Grade 2 >1.5 to 2.0*ULN, Grade 3 >2.0 to 5.0*ULN, Grade 4 >5.0*ULN. Baseline was screening or Day 1, prior to first dose of drug.

Outcome measures

Measure	Ipilimumab (Process B) n=37 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=38 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Chemistry Laboratory Safety Tests (Non-electrolyte) - All Treated Participants ALT (N=36, 37)	2 participants	1 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Chemistry Laboratory Safety Tests (Non-electrolyte) - All Treated Participants AST (N=36, 37)	2 participants	1 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Chemistry Laboratory Safety Tests (Non-electrolyte) - All Treated Participants Alkaline Phosphatase (N=36, 37)	2 participants	1 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Chemistry Laboratory Safety Tests (Non-electrolyte) - All Treated Participants Amylase (N=35, 35)	0 participants	2 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Chemistry Laboratory Safety Tests (Non-electrolyte) - All Treated Participants Lipase (N=10, 14)	0 participants	1 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Chemistry Laboratory Safety Tests (Non-electrolyte) - All Treated Participants Albumin (N=36, 37)	7 participants	8 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Chemistry Laboratory Safety Tests (Non-electrolyte) - All Treated Participants Creatinine (N= 37, 37)	2 participants	1 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Chemistry Laboratory Safety Tests (Non-electrolyte) - All Treated Participants Bilirubin (N=36, 37)	2 participants	0 participants

SECONDARY outcome

Timeframe: Screening to data cut off for July 2010, approximately 36 Weeks

Population: All participants who received at least 1 dose of ipilimumab and had available data at baseline and post baseline.

Sodium high (H) Gr 1:>ULN - 150; Gr 2: >150 - 155; Gr 3: >155 - 160; Gr 4: >160 mmol/L; Sodium low(L) Gr 1:<LLN - 130; Gr 3: <130 - 120; Gr 4: <120 mmol/L. Potassium (H) Gr 1: >ULN - 5.5; Gr 2: >5.5 - 6.0; Gr 3: > 6.0 - 7.0; Gr 4: >7.0 mmol/L; Potassium (L) Gr 1: <LLN - 3.0; Gr 2: <LLN - 3.0; Gr 3: < 3.0 - 2.5; Gr 4: <2.5 mmol/L. Bicarbonate Gr1: 16-<LLN, Gr2: 11-16, Gr3, 8-11, Gr4: <8 milliequivalents per liter (mEq/L). Phosphorus Gr 1: 2.5 - <LLN, Gr2 2.0-<2.5, Gr3: 1.0-<2.0, Gr4: <1.0. Calcium (L) Gr 1: <LLN to 8.0; Gr2: 7.0 - 8.0; Gr3: 6.0-7.0; Gr 4: <6.0 mg/dL; calcium (H) Gr1:>ULN - 11.5, Gr2:>11.5 - 12.5, Gr3: 12.5 - 13.5, Gr4: >13.5. Baseline is screening or Day 1, prior to first dose of drug.

Outcome measures

Measure	Ipilimumab (Process B) n=37 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=38 Participants 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Electrolyte Laboratory Safety Tests - All Treated Participants Inorganic Phosphorus (N=37,37)	9 participants	7 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Electrolyte Laboratory Safety Tests - All Treated Participants Sodium (low) (N=37, 37)	4 participants	6 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Electrolyte Laboratory Safety Tests - All Treated Participants Potassium (low) (N=36, 37)	1 participants	2 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Electrolyte Laboratory Safety Tests - All Treated Participants Potassium (high) (N=36, 37)	0 participants	1 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Electrolyte Laboratory Safety Tests - All Treated Participants Calcium (low) (N=37, 37)	1 participants	7 participants
Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Electrolyte Laboratory Safety Tests - All Treated Participants Bicarbonate (N=37, 37)	0 participants	1 participants

Adverse Events

Ipilimumab (Process B)

Serious events: 24 serious events

Other events: 37 other events

Deaths: 0 deaths

Ipilimumab (Process C)

Serious events: 26 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ipilimumab (Process B) n=37 participants at risk 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=38 participants at risk 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Gastrointestinal disorders Abdominal distension	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Chest pain	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Guillain-Barre syndrome	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Hepatobiliary disorders Hepatic function abnormal	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Endocrine disorders Hypophysitis	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Vascular disorders Hypotension	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Myasthenia gravis	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Pseudomonas infection	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Vomiting	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Psychiatric disorders Alcohol withdrawal syndrome	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Cardiac disorders Atrial flutter	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Gastritis	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Endocrine disorders Hypopituitarism	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Hepatobiliary disorders Bile duct obstruction	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Cognitive disorder	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Dehydration	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Dizziness	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Encephalopathy	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Fatigue	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations H1N1 influenza	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Intestinal perforation	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Lethargy	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Localised oedema	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Psychiatric disorders Mental status changes	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Musculoskeletal and connective tissue disorders Neck pain	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Oedema peripheral	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Eye disorders Uveitis	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Abdominal pain	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Endocrine disorders Adrenal insufficiency	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Cerebral haemorrhage	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Generalised oedema	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Haemorrhage intracranial	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Nausea	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Pyrexia	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Renal and urinary disorders Renal failure acute	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer metastatic	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Asthenia	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Headache	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to adrenals	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Pneumonia	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Septic shock	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Cardiac disorders Acute myocardial infarction	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Cellulitis	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Colitis	10.8% 4/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	21.1% 8/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Psychiatric disorders Confusional state	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Platelet count decreased	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Musculoskeletal and connective tissue disorders Polymyalgia rheumatica	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Sepsis	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Spinal cord compression	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Vascular disorders Temporal arteritis	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Amylase increased	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Ascites	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Hepatobiliary disorders Autoimmune hepatitis	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Infection	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	32.4% 12/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	15.8% 6/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic squamous cell carcinoma	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Pancreatitis	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Renal and urinary disorders Renal failure	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Colonic obstruction	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Diarrhoea	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Musculoskeletal and connective tissue disorders Flank pain	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Lipase increased	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Tremor	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Wound infection	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.

Other adverse events

Measure	Ipilimumab (Process B) n=37 participants at risk 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process B, ipilimumab was manufactured by Lonza using material from transfectoma cell line.	Ipilimumab (Process C) n=38 participants at risk 10 mg/kg ipilimumab was given IV once every 3 weeks (up to 4 doses) in the induction phase (Weeks 1, 4, 7, and 10); it was given once every 12 weeks in the maintenance phase for 48 weeks. In Process C, ipilimumab was manufactured by the Sponsor using material from a sub-clone of the original transfectoma cell line, modified cell culture and purification steps.
Gastrointestinal disorders Abdominal distension	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Blastocystis infection	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Chest pain	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Chills	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	10.5% 4/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.8% 4/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	21.1% 8/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Hypoaesthesia	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Endocrine disorders Hypophysitis	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Vascular disorders Hypotension	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Influenza like illness	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Mucosal inflammation	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	10.5% 4/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Renal and urinary disorders Pollakiuria	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Syncope	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Vomiting	18.9% 7/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	34.2% 13/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations White blood cell count decreased	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Upper respiratory tract infection	16.2% 6/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	10.5% 4/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Musculoskeletal and connective tissue disorders Back pain	18.9% 7/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	21.1% 8/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Candidiasis	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Psychiatric disorders Depression	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Hepatobiliary disorders Hyperbilirubinaemia	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Oral herpes	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Peripheral sensory neuropathy	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	10.5% 4/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Abdominal pain upper	10.8% 4/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Alanine aminotransferase increased	16.2% 6/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	10.5% 4/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Injury, poisoning and procedural complications Contusion	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Dehydration	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	13.2% 5/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Dizziness	10.8% 4/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Dysphagia	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Fatigue	78.4% 29/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	57.9% 22/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Haemoglobin decreased	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	13.2% 5/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Musculoskeletal and connective tissue disorders Myalgia	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Musculoskeletal and connective tissue disorders Neck pain	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	15.8% 6/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Oedema peripheral	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	18.4% 7/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Pain	16.2% 6/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	10.5% 4/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Renal and urinary disorders Urinary retention	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Eye disorders Uveitis	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Abdominal pain	13.5% 5/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	31.6% 12/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Psychiatric disorders Agitation	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Skin and subcutaneous tissue disorders Alopecia	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Cough	18.9% 7/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	21.1% 8/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Dysgeusia	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Flatulence	10.8% 4/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Hypocalcaemia	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Hyponatraemia	16.2% 6/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	13.2% 5/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Nasopharyngitis	13.5% 5/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Nausea	37.8% 14/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	50.0% 19/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Neutrophil count decreased	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Pyrexia	18.9% 7/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	18.4% 7/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Skin and subcutaneous tissue disorders Rash pruritic	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Rhinitis	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Skin and subcutaneous tissue disorders Vitiligo	21.6% 8/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Musculoskeletal and connective tissue disorders Arthralgia	21.6% 8/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	18.4% 7/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Asthenia	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Decreased appetite	37.8% 14/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	36.8% 14/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Dyspepsia	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	18.4% 7/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Haemorrhoids	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Headache	24.3% 9/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	36.8% 14/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Vascular disorders Hot flush	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Hyperglycaemia	13.5% 5/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	18.4% 7/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Hyperkalaemia	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Hypomagnesaemia	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Endocrine disorders Hypothyroidism	10.8% 4/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	13.2% 5/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Psychiatric disorders Mood swings	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Musculoskeletal and connective tissue disorders Muscular weakness	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	13.2% 5/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Oedema	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Pneumonia	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Sinus congestion	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Abdominal discomfort	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Blood and lymphatic system disorders Anaemia	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Aspartate aminotransferase increased	13.5% 5/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	13.2% 5/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Blood creatinine increased	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Blood testosterone decreased	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Bronchial secretion retention	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Cellulitis	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Colitis	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Psychiatric disorders Confusional state	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Vascular disorders Flushing	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	0.00% 0/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Influenza	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Neuropathy peripheral	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Platelet count decreased	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Skin and subcutaneous tissue disorders Pruritus	51.4% 19/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	63.2% 24/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Stomatitis	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Weight increased	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Amylase increased	10.8% 4/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Ascites	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Blood alkaline phosphatase increased	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Blood bilirubin increased	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Constipation	24.3% 9/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	42.1% 16/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Skin and subcutaneous tissue disorders Dry skin	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Hypercalcaemia	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Hypokalaemia	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Psychiatric disorders Insomnia	18.9% 7/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Musculoskeletal and connective tissue disorders Pain in extremity	13.5% 5/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	15.8% 6/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Respiratory, thoracic and mediastinal disorders Productive cough	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Skin and subcutaneous tissue disorders Rash	56.8% 21/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	65.8% 25/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Sinusitis	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Urinary tract infection	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Psychiatric disorders Anxiety	10.8% 4/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	10.5% 4/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Eye disorders Conjunctivitis	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Skin and subcutaneous tissue disorders Decubitus ulcer	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Gastrointestinal disorders Diarrhoea	48.6% 18/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	68.4% 26/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Metabolism and nutrition disorders Hypoalbuminaemia	10.8% 4/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	10.5% 4/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Lipase increased	10.8% 4/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
General disorders Nodule	5.4% 2/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	7.9% 3/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Infections and infestations Oral candidiasis	8.1% 3/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	2.6% 1/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Nervous system disorders Paraesthesia	0.00% 0/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	5.3% 2/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Eye disorders Vision blurred	2.7% 1/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	10.5% 4/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.
Investigations Weight decreased	16.2% 6/37 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.	13.2% 5/38 • Day 1 to last patient, last visit, approximately 3 years. SAEs and AEs 5% threshold up to last patient, last visit (31 Oct 2012) were in primary endpoint posting. Therefore, SAEs and AEs have not changed with this current PRS update from Maintenance Period. SAE/AE upload includes SAEs reported after the data cut off for the clinical study report and thus differs slightly from data in Outcome measure 11.

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