Trial Outcomes & Findings for Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Japanese Patients With Type 2 Diabetes Mellitus (NCT NCT02489968)

Last Updated: 2018-09-06

Results Overview

Change from baseline in HbA1c (%) after 24 weeks of treatment with double-blind trial medication. Change was calculated as: HbA1c value at 24-week - HbA1c value at baseline, for each patient. Baseline was defined as the last observation before the first intake of double-blind randomised trial medication. Statistical analysis presented is based on a restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach. Full Analysis Set (Observed Cases) \[FAS (OC)\]: This analysis set consisted of all patients who were randomised and treated with at least 1 dose of trial drug during the double-blind part of the trial and who had a baseline HbA1c assessment and at least 1 on-treatment HbA1c assessment during the 24-week double-blind part of the trial. Observed cases analysis included only the available data that were observed while patients were on treatment, i.e., excluding the missing data.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

880 participants

Primary outcome timeframe

Baseline and 24 week

Results posted on

2018-09-06

Participant Flow

880 subjects started the open label period

Participant milestones

Participant milestones
Measure	Empagliflozin 10 mg OL Patients were administered empagliflozin 10 milligram (mg) tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.	Empagliflozin 25 mg OL Patients were administered empagliflozin 25 mg tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.	Empagliflozin 10 mg + Linagliptin 5 mg Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive a fixed dose combination (FDC) tablet of empagliflozin 10 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 10 mg, orally with water, once daily for 24-weeks of double-blind treatment period.	Empagliflozin 10 mg + Placebo Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive empagliflozin 10 mg along with a matching placebo of the FDC tablet of empagliflozin 10 mg and linagliptin 5 mg, orally with water, once daily for 24-weeks of double-blind treatment period.	Empagliflozin 25 mg + Linagliptin 5 mg Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive a FDC tablet of empagliflozin 25 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 25 mg, orally with water, once daily for 52-weeks of double-blind treatment period.	Empagliflozin 25 mg + Placebo Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive empagliflozin 25 mg along with a matching placebo of the FDC tablet of empagliflozin 25 mg and linagliptin 5 mg, orally with water, once daily for 52-weeks of double-blind treatment period.
Open-label Treatment Period STARTED	439	440	0	0	0	0
Open-label Treatment Period COMPLETED	215	232	0	0	0	0
Open-label Treatment Period NOT COMPLETED	224	208	0	0	0	0
Double-blind Treatment Period STARTED	0	0	107	108	116	116
Double-blind Treatment Period COMPLETED	0	0	105	100	110	108
Double-blind Treatment Period NOT COMPLETED	0	0	2	8	6	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Empagliflozin 10 mg OL Patients were administered empagliflozin 10 milligram (mg) tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.	Empagliflozin 25 mg OL Patients were administered empagliflozin 25 mg tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.	Empagliflozin 10 mg + Linagliptin 5 mg Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive a fixed dose combination (FDC) tablet of empagliflozin 10 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 10 mg, orally with water, once daily for 24-weeks of double-blind treatment period.	Empagliflozin 10 mg + Placebo Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive empagliflozin 10 mg along with a matching placebo of the FDC tablet of empagliflozin 10 mg and linagliptin 5 mg, orally with water, once daily for 24-weeks of double-blind treatment period.	Empagliflozin 25 mg + Linagliptin 5 mg Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive a FDC tablet of empagliflozin 25 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 25 mg, orally with water, once daily for 52-weeks of double-blind treatment period.	Empagliflozin 25 mg + Placebo Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive empagliflozin 25 mg along with a matching placebo of the FDC tablet of empagliflozin 25 mg and linagliptin 5 mg, orally with water, once daily for 52-weeks of double-blind treatment period.
Open-label Treatment Period Adverse Event	14	7	0	0	0	0
Open-label Treatment Period Protocol Violation	2	2	0	0	0	0
Open-label Treatment Period Lost to Follow-up	0	3	0	0	0	0
Open-label Treatment Period Withdrawal by Subject	4	7	0	0	0	0
Open-label Treatment Period Other than specified above	204	189	0	0	0	0
Double-blind Treatment Period Adverse Event	0	0	2	6	4	5
Double-blind Treatment Period Protocol Violation	0	0	0	0	1	1
Double-blind Treatment Period Withdrawal by Subject	0	0	0	2	0	2
Double-blind Treatment Period Other than specified above	0	0	0	0	1	0

Baseline Characteristics

Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Japanese Patients With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Empagliflozin 10 mg OL n=435 Participants Patients were administered empagliflozin 10 milligram (mg) tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.	Empagliflozin 25 mg OL n=433 Participants Patients were administered empagliflozin 25 mg tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.	Total n=868 Participants Total of all reporting groups
Age, Continuous	56.8 Years STANDARD_DEVIATION 10.2 • n=5 Participants	57.5 Years STANDARD_DEVIATION 10.0 • n=7 Participants	57.2 Years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	111 Participants n=5 Participants	124 Participants n=7 Participants	235 Participants n=5 Participants
Sex: Female, Male Male	324 Participants n=5 Participants	309 Participants n=7 Participants	633 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 24 week

Population: FAS (OC)

Outcome measures

Outcome measures
Measure	Empagliflozin 10 mg + Linagliptin 5 mg n=103 Participants Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive a fixed dose combination (FDC) tablet of empagliflozin 10 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 10 mg, orally with water, once daily for 24-weeks of double-blind treatment period.	Empagliflozin 10 mg + Placebo n=96 Participants Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive empagliflozin 10 mg along with a matching placebo of the FDC tablet of empagliflozin 10 mg and linagliptin 5 mg, orally with water, once daily for 24-weeks of double-blind treatment period.	Empagliflozin 25 mg + Linagliptin 5 mg n=111 Participants Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive a FDC tablet of empagliflozin 25 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 25 mg, orally with water, once daily for 52-weeks of double-blind treatment period.	Empagliflozin 25 mg + Placebo n=108 Participants Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive empagliflozin 25 mg along with a matching placebo of the FDC tablet of empagliflozin 25 mg and linagliptin 5 mg, orally with water, once daily for 52-weeks of double-blind treatment period.
Change in Glycated Haemoglobin A1c (HbA1c) (%) From Baseline After 24 Weeks of Treatment	-0.94 Percentage (%) Standard Error 0.05	-0.12 Percentage (%) Standard Error 0.06	-0.91 Percentage (%) Standard Error 0.05	-0.33 Percentage (%) Standard Error 0.05

Adverse Events

Empagliflozin 25 mg + Linagliptin 5 mg

Serious events: 6 serious events

Other events: 54 other events

Deaths: 0 deaths

Empagliflozin 10 mg + Linagliptin 5 mg

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Empagliflozin 25 mg + Placebo

Serious events: 8 serious events

Other events: 51 other events

Deaths: 0 deaths

Empagliflozin 10 mg + Placebo

Serious events: 4 serious events

Other events: 36 other events

Deaths: 0 deaths

Empagliflozin 25 mg OL

Serious events: 11 serious events

Other events: 131 other events

Deaths: 0 deaths

Empagliflozin 10 mg OL

Serious events: 9 serious events

Other events: 120 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Empagliflozin 25 mg + Linagliptin 5 mg n=116 participants at risk Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive a FDC tablet of empagliflozin 25 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 25 mg, orally with water, once daily for 52-weeks of double-blind treatment period.	Empagliflozin 10 mg + Linagliptin 5 mg n=107 participants at risk Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive a fixed dose combination (FDC) tablet of empagliflozin 10 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 10 mg, orally with water, once daily for 24-weeks of double-blind treatment period.	Empagliflozin 25 mg + Placebo n=116 participants at risk Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive empagliflozin 25 mg along with a matching placebo of the FDC tablet of empagliflozin 25 mg and linagliptin 5 mg, orally with water, once daily for 52-weeks of double-blind treatment period.	Empagliflozin 10 mg + Placebo n=108 participants at risk Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive empagliflozin 10 mg along with a matching placebo of the FDC tablet of empagliflozin 10 mg and linagliptin 5 mg, orally with water, once daily for 24-weeks of double-blind treatment period.	Empagliflozin 25 mg OL n=440 participants at risk Patients were administered empagliflozin 25 mg tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.	Empagliflozin 10 mg OL n=439 participants at risk Patients were administered empagliflozin 10 milligram (mg) tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.93% 1/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Infections and infestations Sepsis	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.93% 1/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Infections and infestations Appendicitis	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.45% 2/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Infections and infestations Diabetic gangrene	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Infections and infestations Diverticulitis	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Infections and infestations Viral infection	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph nodes	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.93% 1/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphangioma	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.93% 1/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Blood and lymphatic system disorders Immune thrombocytopenic purpura	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Immune system disorders Anaphylactic shock	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Metabolism and nutrition disorders Dehydration	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Nervous system disorders Cerebral infarction	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Nervous system disorders Lateral medullary syndrome	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Eye disorders Cataract	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Ear and labyrinth disorders Sudden hearing loss	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Cardiac disorders Acute myocardial infarction	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.93% 1/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Cardiac disorders Atrial flutter	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.93% 1/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Cardiac disorders Ventricular hypokinesia	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Gastrointestinal disorders Colitis ischaemic	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Hepatobiliary disorders Cholangitis	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.93% 1/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Hepatobiliary disorders Drug-induced liver injury	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.45% 2/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Renal and urinary disorders Ureterolithiasis	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Renal and urinary disorders Hydronephrosis	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Investigations Glycosylated haemoglobin increased	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Injury, poisoning and procedural complications Rib fracture	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Injury, poisoning and procedural complications Torus fracture	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.23% 1/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Infections and infestations Hepatitis E	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Ear and labyrinth disorders Deafness neurosensory	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Ear and labyrinth disorders Vertigo positional	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Cardiac disorders Angina pectoris	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Respiratory, thoracic and mediastinal disorders Mediastinal cyst	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Gastrointestinal disorders Duodenitis	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.86% 1/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).

Other adverse events

Other adverse events
Measure	Empagliflozin 25 mg + Linagliptin 5 mg n=116 participants at risk Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive a FDC tablet of empagliflozin 25 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 25 mg, orally with water, once daily for 52-weeks of double-blind treatment period.	Empagliflozin 10 mg + Linagliptin 5 mg n=107 participants at risk Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive a fixed dose combination (FDC) tablet of empagliflozin 10 mg and linagliptin 5 mg along with a matching placebo of empagliflozin 10 mg, orally with water, once daily for 24-weeks of double-blind treatment period.	Empagliflozin 25 mg + Placebo n=116 participants at risk Patients who received empagliflozin 25 mg during open-label stabilisation period were randomized to receive empagliflozin 25 mg along with a matching placebo of the FDC tablet of empagliflozin 25 mg and linagliptin 5 mg, orally with water, once daily for 52-weeks of double-blind treatment period.	Empagliflozin 10 mg + Placebo n=108 participants at risk Patients who received empagliflozin 10 mg during open-label stabilisation period were randomized to receive empagliflozin 10 mg along with a matching placebo of the FDC tablet of empagliflozin 10 mg and linagliptin 5 mg, orally with water, once daily for 24-weeks of double-blind treatment period.	Empagliflozin 25 mg OL n=440 participants at risk Patients were administered empagliflozin 25 mg tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.	Empagliflozin 10 mg OL n=439 participants at risk Patients were administered empagliflozin 10 milligram (mg) tablets, orally with water, once daily for 16-weeks of open-label stabilisation period.
Renal and urinary disorders Pollakiuria	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.93% 1/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	8.0% 35/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	6.8% 30/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Investigations Blood ketone body increased	13.8% 16/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	1.9% 2/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	7.8% 9/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	10.2% 11/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	9.1% 40/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	5.9% 26/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Investigations Weight decreased	1.7% 2/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	6.0% 7/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.93% 1/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	2.3% 10/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	3.6% 16/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Infections and infestations Viral upper respiratory tract infection	26.7% 31/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	15.0% 16/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	29.3% 34/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	22.2% 24/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	10.5% 46/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	10.7% 47/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Infections and infestations Periodontitis	2.6% 3/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	5.2% 6/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.93% 1/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.45% 2/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.46% 2/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Gastrointestinal disorders Constipation	4.3% 5/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	1.9% 2/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	5.2% 6/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.00% 0/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	2.5% 11/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	2.3% 10/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Musculoskeletal and connective tissue disorders Back pain	6.0% 7/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	2.8% 3/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	1.7% 2/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	2.8% 3/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	1.1% 5/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.46% 2/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).
Injury, poisoning and procedural complications Contusion	3.4% 4/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	2.8% 3/107 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	5.2% 6/116 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.93% 1/108 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.68% 3/440 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).	0.91% 4/439 • From first drug administration till two weeks after last drug administration; up to 72 weeks (including 16 weeks open-label, 2 weeks run-in period and 52 weeks double-blind treatment period). All patients who were randomised and treated with at least 1 dose of trial drug during open-label and double-blind part of the trial. Adverse events were coded using the MedDRA coding system version 19.1 (Week 24 analysis) and version 20.0 (Week 52 analysis).

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