Trial Outcomes & Findings for Taribavirin Phase 2 Dose Finding Study for the Treatment of Hepatitis C Virus (HCV) (NCT NCT00446134)

NCT ID: NCT00446134

Last Updated: 2012-07-27

Results Overview

The primary efficacy endpoint was the numbers of responders at Treatment Week (TW) 12. Responders are defined as patients achieving either viral negativity or a partial response (PR). Viral negativity is defined as \<100 copies/mL serum HCV RNA. A PR is defined as \< 100 copies/mL serum HCV RNA and at least a 2-log decrease from baseline in serum HCV RNA levels. Responder rates with corresponding 95% confidence intervals were estimated for each treatment group.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 278 participants
• Primary outcome timeframe: Treatment Week 12
• Results posted on: 2012-07-27

Participant Flow

Patients who met all entry criteria and signed an informed consent were randomized in a 1:1:1:1 ratio to one of the 4 arms by a central randomization schedule. A total of 51 clinical centers in the United States participated in the study. 278 patients were randomized; 275 patients who receive one dose of study drug were included in all analyses.

Randomization was stratified by screening HCV RNA viral load less than or = to 2 or greater than (>) 2 million copies/mL and body weight (BW) (less than or = 75 or >75 kg). A cap of 70% was set for patients with BWs >75 kg so that at least 30% of the patients in each group have BWs less than or = to 75 kg.

Participant milestones

Measure	Taribavirin 20 mg/kg/Day Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 25 mg/kg/Day Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 30 mg/kg/Day Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Ribavirin 800 mg/Day Oral ribavirin 800 mg/day (body weight \<65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
Overall Study STARTED	69	70	69	70
Overall Study COMPLETED	35	25	26	25
Overall Study NOT COMPLETED	34	45	43	45

Reasons for withdrawal

Measure	Taribavirin 20 mg/kg/Day Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 25 mg/kg/Day Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 30 mg/kg/Day Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Ribavirin 800 mg/Day Oral ribavirin 800 mg/day (body weight \<65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
Overall Study Adverse Event	7	17	13	18
Overall Study Lack of Efficacy	19	19	24	19
Overall Study Protocol Violation	0	2	1	0
Overall Study Lost to Follow-up	1	3	1	1
Overall Study Withdrawal by Subject	3	3	1	3
Overall Study Physician Decision	0	0	0	2
Overall Study Adverse Event-Diarrhea	1	1	2	0
Overall Study Reason Not Completed	3	0	1	2

Baseline Characteristics

Taribavirin Phase 2 Dose Finding Study for the Treatment of Hepatitis C Virus (HCV)

Baseline characteristics by cohort

Measure	Taribavirin 20 mg/kg/Day n=67 Participants Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 25 mg/kg/Day n=70 Participants Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 30 mg/kg/Day n=68 Participants Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Ribavirin 800 mg/Day n=70 Participants Oral ribavirin 800 mg/day (body weight \<65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Total n=275 Participants Total of all reporting groups
Age Continuous	48.5 years STANDARD_DEVIATION 9.39 • n=5 Participants	47.5 years STANDARD_DEVIATION 9.42 • n=7 Participants	49.6 years STANDARD_DEVIATION 7.24 • n=5 Participants	49.7 years STANDARD_DEVIATION 8.30 • n=4 Participants	48.8 years STANDARD_DEVIATION 8.63 • n=21 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	25 Participants n=7 Participants	25 Participants n=5 Participants	22 Participants n=4 Participants	107 Participants n=21 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	45 Participants n=7 Participants	43 Participants n=5 Participants	48 Participants n=4 Participants	168 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	11 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	14 Participants n=7 Participants	13 Participants n=5 Participants	12 Participants n=4 Participants	49 Participants n=21 Participants
Race (NIH/OMB) White	50 Participants n=5 Participants	41 Participants n=7 Participants	42 Participants n=5 Participants	45 Participants n=4 Participants	178 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	11 Participants n=4 Participants	37 Participants n=21 Participants
Weight	81.5 kilograms STANDARD_DEVIATION 16.9 • n=5 Participants	82.6 kilograms STANDARD_DEVIATION 16.8 • n=7 Participants	82.2 kilograms STANDARD_DEVIATION 18.0 • n=5 Participants	82.3 kilograms STANDARD_DEVIATION 17.1 • n=4 Participants	82.1 kilograms STANDARD_DEVIATION 17.09 • n=21 Participants
Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) (log 10)	6.6 Copies/mL STANDARD_DEVIATION 0.71 • n=5 Participants	6.6 Copies/mL STANDARD_DEVIATION 0.78 • n=7 Participants	6.6 Copies/mL STANDARD_DEVIATION 0.78 • n=5 Participants	6.5 Copies/mL STANDARD_DEVIATION 0.84 • n=4 Participants	6.6 Copies/mL STANDARD_DEVIATION 0.77 • n=21 Participants

PRIMARY outcome

Timeframe: Treatment Week 12

Population: The primary efficacy analysis was performed using the Intent-to-Treat (ITT) population and 275 patients who received at least one dose of study drug were analyzed for efficacy.

The primary efficacy endpoint was the numbers of responders at Treatment Week (TW) 12. Responders are defined as patients achieving either viral negativity or a partial response (PR). Viral negativity is defined as <100 copies/mL serum HCV RNA. A PR is defined as < 100 copies/mL serum HCV RNA and at least a 2-log decrease from baseline in serum HCV RNA levels. Responder rates with corresponding 95% confidence intervals were estimated for each treatment group.

Outcome measures

Measure	Taribavirin 20 mg/kg/Day n=67 Participants Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 25 mg/kg/Day n=70 Participants Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 30 mg/kg/Day n=68 Participants Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Ribavirin 800 mg/Day n=70 Participants Oral ribavirin 800 mg/day (body weight \<65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
Patients With Either Undetectable Serum HCV RNA (<100 Copies/ml) or at Least a 2-log Decrease From Baseline in Serum Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Treatment Week 12. Early Virologic Response (EVR) (less than 100)	43 Participants	40 Participants	37 Participants	36 Participants
Patients With Either Undetectable Serum HCV RNA (<100 Copies/ml) or at Least a 2-log Decrease From Baseline in Serum Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Treatment Week 12. No EVR (non-responder, Total)	24 Participants	30 Participants	31 Participants	34 Participants
Patients With Either Undetectable Serum HCV RNA (<100 Copies/ml) or at Least a 2-log Decrease From Baseline in Serum Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Treatment Week 12. Detectable (greater than 100 copies/mL at TW 12)	17 Participants	17 Participants	21 Participants	19 Participants
Patients With Either Undetectable Serum HCV RNA (<100 Copies/ml) or at Least a 2-log Decrease From Baseline in Serum Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Treatment Week 12. Discontinued (Prior to TW 12)	7 Participants	12 Participants	10 Participants	15 Participants
Patients With Either Undetectable Serum HCV RNA (<100 Copies/ml) or at Least a 2-log Decrease From Baseline in Serum Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Treatment Week 12. Missing (No value at TW 12)	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Treatment Week Follow-Up 24

Population: The secondary analysis was performed using the Safety Population and 275 patients who received at least one dose of study drug were analyzed for safety.

The primary safety endpoint will be the numbers of patients with hemoglobin <10 g/dL (anemia) at any time during the treatment period. The comparison of anemia rates between taribavirin and ribavirin groups will be carried out using the Fisher's exact test or Chi-square test. The 95% confidence interval of the difference in proportion will be analyzed.

Outcome measures

Measure	Taribavirin 20 mg/kg/Day n=67 Participants Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 25 mg/kg/Day n=70 Participants Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 30 mg/kg/Day n=68 Participants Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Ribavirin 800 mg/Day n=70 Participants Oral ribavirin 800 mg/day (body weight \<65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
Patients With Anemia (Hemoglobin <10 g/dL) Up to Follow-up Week 24	11 Participants	11 Participants	19 Participants	23 Participants

SECONDARY outcome

Timeframe: Treatment Week Follow-Up 24

Population: This analysis was performed using the Intent-to-Treat Population (ITT); undetectable HCV RNA defined as \<100 copies/mL;Patients with a missing value at TW 12, TW 24 were considered Non-responders (detectable); a responder is defined as a patient with undetectable HCV RNA at FW 24 after achieving EVR at TW 12 and undetectable status at TW 24

Outcome measures

Measure	Taribavirin 20 mg/kg/Day n=67 Participants Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 25 mg/kg/Day n=70 Participants Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 30 mg/kg/Day n=68 Participants Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Ribavirin 800 mg/Day n=70 Participants Oral ribavirin 800 mg/day (body weight \<65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
Patients With Undetected Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) (<100 Copies/mL) at Treatment Week Follow-Up 24 Discontinued Week Follow-Up Week 24	34 Participants	36 Participants	33 Participants	37 Participants
Patients With Undetected Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) (<100 Copies/mL) at Treatment Week Follow-Up 24 Responder Follow-Up Week 24	19 Participants	19 Participants	19 Participants	19 Participants
Patients With Undetected Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) (<100 Copies/mL) at Treatment Week Follow-Up 24 Non-Responder Follow-Up Week 24	48 Participants	51 Participants	49 Participants	51 Participants
Patients With Undetected Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) (<100 Copies/mL) at Treatment Week Follow-Up 24 Detectable HCV RNA Follow-Up Week 24	14 Participants	15 Participants	16 Participants	14 Participants

SECONDARY outcome

Timeframe: Follow-Up Week 24

Population: The analysis was performed using patients who had undetectable HVC RNA at their last visit on drug.

Includes patients who had undetectable Hepatitis Virus C (HVC) Ribonucleic Acid (RNA) at their last visit on drug.

Outcome measures

Measure	Taribavirin 20 mg/kg/Day n=29 Participants Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 25 mg/kg/Day n=24 Participants Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 30 mg/kg/Day n=22 Participants Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Ribavirin 800 mg/Day n=24 Participants Oral ribavirin 800 mg/day (body weight \<65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
Relapsers at Follow-Up Visit 24	10 Participants Interval -10.08 to 20.86	5 Participants Interval -22.98 to 10.23	3 Participants Interval -28.87 to 17.66	5 Participants

Adverse Events

Taribavirin 20 mg/kg/Day

Serious events: 7 serious events

Other events: 66 other events

Deaths: 0 deaths

Taribavirin 25 mg/kg/Day

Serious events: 6 serious events

Other events: 68 other events

Deaths: 0 deaths

Taribavirin 30 mg/kg/Day

Serious events: 6 serious events

Other events: 68 other events

Deaths: 0 deaths

Ribavirin 800 mg/Day

Serious events: 9 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Measure	Taribavirin 20 mg/kg/Day n=67 participants at risk Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 25 mg/kg/Day n=70 participants at risk Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 30 mg/kg/Day n=68 participants at risk Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Ribavirin 800 mg/Day n=70 participants at risk Oral ribavirin 800 mg/day (body weight \<65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
Infections and infestations Pneumonia	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/68 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Infections and infestations Appendicitis	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Infections and infestations Sepsis	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Infections and infestations Abscess Jaw	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Infections and infestations Injection Site Cellulitis	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Infections and infestations Empyema	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Cardiac disorders Angina Pectoris	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Cardiac disorders Atrial Fibrillation	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Delirium	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Intentional Self-injury	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Suicidal Ideation	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.3% 3/70 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Depression	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Anxiety	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Mental Status Changes	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Suicide Attempt	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Diarrhoea	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Upper Gastrointestinal Haemorrhage	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Colitis	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Metabolism and nutrition disorders Dehydration	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Nervous system disorders Metabolic Encaphalopathy	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Nervous system disorders Status Epilepticus	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Nervous system disorders Cerebrovascular Accident	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Nervous system disorders Convulsion	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Nervous system disorders Migraine	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Nervous system disorders Syncope	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Distress Disorder	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
General disorders Chest Pain	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
General disorders Asthenia	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Hepatobiliary disorders Cholecystitis	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Injury, poisoning and procedural complications Accidental Overdose	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Injury, poisoning and procedural complications Fibula Fracture	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Injury, poisoning and procedural complications Tibia Fracture	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric Cancer	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal Adenocarcinoma	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal Squamous Cell Carcinoma	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Vascular disorders Deep Vein Thrombosis	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.

Other adverse events

Measure	Taribavirin 20 mg/kg/Day n=67 participants at risk Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 25 mg/kg/Day n=70 participants at risk Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Taribavirin 30 mg/kg/Day n=68 participants at risk Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Ribavirin 800 mg/Day n=70 participants at risk Oral ribavirin 800 mg/day (body weight \<65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
General disorders Fatigue	65.7% 44/67 • Number of events 44 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	52.9% 37/70 • Number of events 37 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	63.2% 43/68 • Number of events 43 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	51.4% 36/70 • Number of events 36 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Nausea	44.8% 30/67 • Number of events 30 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	34.3% 24/70 • Number of events 24 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	42.6% 29/68 • Number of events 29 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	41.4% 29/70 • Number of events 29 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
General disorders Influenza-like Illness	29.9% 20/67 • Number of events 20 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	30.0% 21/70 • Number of events 21 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	39.7% 27/68 • Number of events 27 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	34.3% 24/70 • Number of events 24 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Diarrhoea	40.3% 27/67 • Number of events 27 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	38.6% 27/70 • Number of events 27 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	36.8% 25/68 • Number of events 25 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	22.9% 16/70 • Number of events 16 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Insomnia	34.3% 23/67 • Number of events 23 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	37.1% 26/70 • Number of events 26 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	33.8% 23/68 • Number of events 23 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	24.3% 17/70 • Number of events 17 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Nervous system disorders Headache	44.8% 30/67 • Number of events 30 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	50.0% 35/70 • Number of events 35 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	32.4% 22/68 • Number of events 22 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	40.0% 28/70 • Number of events 28 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
General disorders Chills	25.4% 17/67 • Number of events 17 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	22.9% 16/70 • Number of events 16 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	30.9% 21/68 • Number of events 21 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	20.0% 14/70 • Number of events 14 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Irritability	23.9% 16/67 • Number of events 16 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	17.1% 12/70 • Number of events 12 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	26.5% 18/68 • Number of events 18 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	22.9% 16/70 • Number of events 16 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Musculoskeletal and connective tissue disorders Myalgia	31.3% 21/67 • Number of events 21 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	15.7% 11/70 • Number of events 11 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	25.0% 17/68 • Number of events 17 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	20.0% 14/70 • Number of events 14 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Metabolism and nutrition disorders Decreased Appetite	16.4% 11/67 • Number of events 11 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.1% 5/70 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	25.0% 17/68 • Number of events 17 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	14.3% 10/70 • Number of events 10 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Depression	19.4% 13/67 • Number of events 13 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	34.3% 24/70 • Number of events 24 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	23.5% 16/68 • Number of events 16 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	14.3% 10/70 • Number of events 10 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Musculoskeletal and connective tissue disorders Arthralgia	20.9% 14/67 • Number of events 14 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	15.7% 11/70 • Number of events 11 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	22.1% 15/68 • Number of events 15 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	24.3% 17/70 • Number of events 17 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
General disorders Injection Site Erythema	29.9% 20/67 • Number of events 20 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	12.9% 9/70 • Number of events 9 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	22.1% 15/68 • Number of events 15 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	24.3% 17/70 • Number of events 17 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Blood and lymphatic system disorders Anaemia	11.9% 8/67 • Number of events 8 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	20.0% 14/70 • Number of events 14 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	22.1% 15/68 • Number of events 15 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	32.9% 23/70 • Number of events 23 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Nervous system disorders Dizziness	14.9% 10/67 • Number of events 10 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	25.7% 18/70 • Number of events 18 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	19.1% 13/68 • Number of events 13 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	21.4% 15/70 • Number of events 15 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Skin and subcutaneous tissue disorders Alopecia	11.9% 8/67 • Number of events 8 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	15.7% 11/70 • Number of events 11 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	17.6% 12/68 • Number of events 12 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	25.7% 18/70 • Number of events 18 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
General disorders Pyrexia	16.4% 11/67 • Number of events 11 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	15.7% 11/70 • Number of events 11 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	17.6% 12/68 • Number of events 12 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	25.7% 18/70 • Number of events 18 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Skin and subcutaneous tissue disorders Rash	16.4% 11/67 • Number of events 11 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	18.6% 13/70 • Number of events 13 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	17.6% 12/68 • Number of events 12 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	17.1% 12/70 • Number of events 12 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Skin and subcutaneous tissue disorders Dry Skin	10.4% 7/67 • Number of events 7 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	20.0% 14/70 • Number of events 14 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	16.2% 11/68 • Number of events 11 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	11.4% 8/70 • Number of events 8 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Blood and lymphatic system disorders Neutropenia	14.9% 10/67 • Number of events 10 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	8.6% 6/70 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	16.2% 11/68 • Number of events 11 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	8.6% 6/70 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
General disorders Pain	9.0% 6/67 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	12.9% 9/70 • Number of events 9 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	14.7% 10/68 • Number of events 10 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	11.4% 8/70 • Number of events 8 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Abdominal Pain	10.4% 7/67 • Number of events 7 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	14.3% 10/70 • Number of events 10 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	14.7% 10/68 • Number of events 10 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.1% 5/70 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.9% 10/67 • Number of events 10 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	13.2% 9/68 • Number of events 9 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	14.3% 10/70 • Number of events 10 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Vomiting	16.4% 11/67 • Number of events 11 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	17.1% 12/70 • Number of events 12 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	13.2% 9/68 • Number of events 9 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.1% 5/70 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Respiratory, thoracic and mediastinal disorders Cough	16.4% 11/67 • Number of events 11 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	14.3% 10/70 • Number of events 10 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	11.8% 8/68 • Number of events 8 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	17.1% 12/70 • Number of events 12 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Skin and subcutaneous tissue disorders Pruritis	16.4% 11/67 • Number of events 11 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	11.4% 8/70 • Number of events 8 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	11.8% 8/68 • Number of events 8 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	18.6% 13/70 • Number of events 13 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Anxiety	11.9% 8/67 • Number of events 8 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	10.0% 7/70 • Number of events 7 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	11.8% 8/68 • Number of events 8 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	10.0% 7/70 • Number of events 7 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Loose Stools	10.4% 7/67 • Number of events 7 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.3% 3/70 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	8.8% 6/68 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Musculoskeletal and connective tissue disorders Back Pain	7.5% 5/67 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	11.4% 8/70 • Number of events 8 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.4% 5/68 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Metabolism and nutrition disorders Anorexia	7.5% 5/67 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.4% 5/68 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	11.4% 8/70 • Number of events 8 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Nervous system disorders Dysgeusia	13.4% 9/67 • Number of events 9 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.4% 5/68 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
General disorders Injection Site Reaction	9.0% 6/67 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	8.6% 6/70 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.4% 3/68 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	11.4% 8/70 • Number of events 8 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Skin and subcutaneous tissue disorders Hypotrichosis	10.4% 7/67 • Number of events 7 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/70 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.4% 3/68 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.1% 5/70 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Constipation	10.4% 7/67 • Number of events 7 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	8.6% 6/70 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/68 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.1% 5/70 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Infections and infestations Sinusitis	13.4% 9/67 • Number of events 9 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	8.6% 6/70 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Investigations Weight Decreased	9.0% 6/67 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.4% 5/68 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.3% 3/70 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Nervous system disorders Disturbance in Attention	9.0% 6/67 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/70 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	8.8% 6/68 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/70 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal Pain	9.0% 6/67 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.4% 3/68 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/70 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Eye disorders Vision Blurred	4.5% 3/67 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.1% 5/70 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.4% 5/68 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.3% 3/70 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
General disorders Asthenia	7.5% 5/67 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.3% 3/70 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.9% 4/68 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.3% 3/70 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Dyspepsia	4.5% 3/67 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.4% 5/68 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.3% 3/70 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Haemorrhoids	4.5% 3/67 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.3% 3/70 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.4% 5/68 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Infection	6.0% 4/67 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	8.6% 6/70 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.1% 5/70 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	6.0% 4/67 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.3% 3/70 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/68 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Respiratory, thoracic and mediastinal disorders Herpes Simplex	6.0% 4/67 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/70 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.4% 3/68 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/70 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Vascular disorders Hypertension	7.5% 5/67 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.4% 3/68 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.3% 3/70 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Infections and infestations Urinary Tract Infection	6.0% 4/67 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/70 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.4% 3/68 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.1% 5/70 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Abdominal Pain Upper	3.0% 2/67 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/68 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.1% 5/70 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
General disorders Injection Site Rash	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.4% 3/68 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Libido Decreased	4.5% 3/67 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Metabolism and nutrition disorders Dehydration	3.0% 2/67 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.9% 4/68 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Skin and subcutaneous tissue disorders Dermatitis	3.0% 2/67 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.0% 2/67 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.3% 3/70 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Nervous system disorders Memory Impairment	6.0% 4/67 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/68 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Mood Swings	3.0% 2/67 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.3% 3/70 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Musculoskeletal and connective tissue disorders Pain in Extremity	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.9% 4/68 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Nervous system disorders Paraesthesia	6.0% 4/67 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Psychiatric disorders Anger	6.0% 4/67 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Flatulence	6.0% 4/67 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Skin and subcutaneous tissue disorders Hyperhidrosis	6.0% 4/67 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/70 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
General disorders Injection Site Pruritus	6.0% 4/67 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Respiratory, thoracic and mediastinal disorders Respiratory Tract Congestion	6.0% 4/67 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Gastrointestinal disorders Dysphagia	3.0% 2/67 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/70 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.1% 5/70 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea Exertional	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/68 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Eye disorders Eye Pain	0.00% 0/67 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	4.4% 3/68 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	7.1% 5/70 • Number of events 5 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
General disorders Non-cardiac Chest Pain	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.4% 1/70 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	2.9% 2/68 • Number of events 2 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	8.6% 6/70 • Number of events 6 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Ear and labyrinth disorders Vertigo	4.5% 3/67 • Number of events 3 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/68 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Infections and infestations Tooth Abscess	1.5% 1/67 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	0.00% 0/70 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	1.5% 1/68 • Number of events 1 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.	5.7% 4/70 • Number of events 4 • Treatment Week Follow-Up 24 A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.

Additional Information

Senior Director Clinical Development

Valeant Pharmaceuticals International, Inc.

Phone: 908-927-1782

Email: ralph.doyle@valeant.com

Results disclosure agreements

• Principal investigator is a sponsor employee Agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Valeant supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER