Trial Outcomes & Findings for Safety and Efficacy of Boceprevir/Peginterferon Alfa-2a/Ribavirin in Interleukin-28B CC Allele-Positive Chronic Hepatitis C Virus (HCV) Genotype 1 Participants (P07755) (NCT NCT01544920)

Last Updated: 2018-09-11

Results Overview

SVR24 rates were determined for all participants in Arm 1 and Arm 2. HCV RNA viral load was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan HCV Test v1.0, which has a lower limit of quantification of 43 IU/mL.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

737 participants

Primary outcome timeframe

Up to Week 74

Results posted on

2018-09-11

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1: Peg-IFN + RBV Participants received an initial 4 week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, participants with undetectable HCV RNA received open label peg-IFN + RBV for an additional 18 weeks (total of 24 weeks of peg-IFN/RBV therapy) \[Arm 1a\]. Participants with detectable HCV RNA at Week 4 had BOC added to the peg-IFN + RBV regimen at Week 6 and then followed the Response Guided Therapy (RGT) regimen for BOC + peg-IFN + RBV \[Arm 1b\].	Arm 2: BOC + Peg-IFN + RBV Participants received an initial 4-week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, all participants had BOC added to the peg-IFN + RBV regimen at Week 6 regardless of HCV RNA levels. Participants who had undetectable HCV RNA at Week 4 continued on the BOC + peg-IFN + RBV regimen for an additional 20 weeks (total of 24 weeks of BOC + peg-IFN + RBV therapy) \[Arm 2a\]. Participants with detectable HCV RNA at Week 4 followed the RGT regimen for BOC + peg-IFN + RBV \[Arm 2b\].
Overall Study STARTED	368	369
Overall Study COMPLETED	349	346
Overall Study NOT COMPLETED	19	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1: Peg-IFN + RBV Participants received an initial 4 week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, participants with undetectable HCV RNA received open label peg-IFN + RBV for an additional 18 weeks (total of 24 weeks of peg-IFN/RBV therapy) \[Arm 1a\]. Participants with detectable HCV RNA at Week 4 had BOC added to the peg-IFN + RBV regimen at Week 6 and then followed the Response Guided Therapy (RGT) regimen for BOC + peg-IFN + RBV \[Arm 1b\].	Arm 2: BOC + Peg-IFN + RBV Participants received an initial 4-week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, all participants had BOC added to the peg-IFN + RBV regimen at Week 6 regardless of HCV RNA levels. Participants who had undetectable HCV RNA at Week 4 continued on the BOC + peg-IFN + RBV regimen for an additional 20 weeks (total of 24 weeks of BOC + peg-IFN + RBV therapy) \[Arm 2a\]. Participants with detectable HCV RNA at Week 4 followed the RGT regimen for BOC + peg-IFN + RBV \[Arm 2b\].
Overall Study Adverse Event	0	3
Overall Study Death	0	1
Overall Study Lost to Follow-up	11	12
Overall Study Protocol Violation	0	2
Overall Study Physician Decision	4	1
Overall Study Withdrawal by Subject	4	4

Baseline Characteristics

Safety and Efficacy of Boceprevir/Peginterferon Alfa-2a/Ribavirin in Interleukin-28B CC Allele-Positive Chronic Hepatitis C Virus (HCV) Genotype 1 Participants (P07755)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Peg-IFN + RBV n=368 Participants Participants received an initial 4 week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, participants with undetectable HCV RNA received open label peg-IFN + RBV for an additional 18 weeks (total of 24 weeks of peg-IFN/RBV therapy) \[Arm 1a\]. Participants with detectable HCV RNA at Week 4 had BOC added to the peg-IFN + RBV regimen at Week 6 and then followed the Response Guided Therapy (RGT) regimen for BOC + peg-IFN + RBV \[Arm 1b\].	Arm 2: BOC + Peg-IFN + RBV n=369 Participants Participants received an initial 4-week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, all participants had BOC added to the peg-IFN + RBV regimen at Week 6 regardless of HCV RNA levels. Participants who had undetectable HCV RNA at Week 4 continued on the BOC + peg-IFN + RBV regimen for an additional 20 weeks (total of 24 weeks of BOC + peg-IFN + RBV therapy) \[Arm 2a\]. Participants with detectable HCV RNA at Week 4 followed the RGT regimen for BOC + peg-IFN + RBV \[Arm 2b\].	Total n=737 Participants Total of all reporting groups
Age, Continuous	43.9 Years STANDARD_DEVIATION 12.0 • n=5 Participants	42.4 Years STANDARD_DEVIATION 12.4 • n=7 Participants	43.1 Years STANDARD_DEVIATION 12.2 • n=5 Participants
Sex: Female, Male Female	167 Participants n=5 Participants	148 Participants n=7 Participants	315 Participants n=5 Participants
Sex: Female, Male Male	201 Participants n=5 Participants	221 Participants n=7 Participants	422 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 74

Population: The Full Analysis Set (FAS) consisted of all participants who completed the 4-week peg-IFN + RBV lead-in and who were randomized at Week 4.

Outcome measures

Outcome measures
Measure	Arm 1: Peg-IFN + RBV n=368 Participants Participants received an initial 4 week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, participants with undetectable HCV RNA received open label peg-IFN + RBV for an additional 18 weeks (total of 24 weeks of peg-IFN/RBV therapy) \[Arm 1a\]. Participants with detectable HCV RNA at Week 4 had BOC added to the peg-IFN + RBV regimen at Week 6 and then followed the Response Guided Therapy (RGT) regimen for BOC + peg-IFN + RBV \[Arm 1b\].	Arm 2: BOC + Peg-IFN + RBV n=369 Participants Participants received an initial 4-week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, all participants had BOC added to the peg-IFN + RBV regimen at Week 6 regardless of HCV RNA levels. Participants who had undetectable HCV RNA at Week 4 continued on the BOC + peg-IFN + RBV regimen for an additional 20 weeks (total of 24 weeks of BOC + peg-IFN + RBV therapy) \[Arm 2a\]. Participants with detectable HCV RNA at Week 4 followed the RGT regimen for BOC + peg-IFN + RBV \[Arm 2b\].
Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) 24 Weeks After Completing Study Treatment (SVR24)	86.7 Percentage of participants	88.3 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: The Full Analysis Set (FAS) consisted of all participants who completed the 4-week peg-IFN + RBV lead-in, who were randomized at Week 4, and also had undetectable HCV RNA at Week 4.

SVR24 rates were determined for only participants that had undetectable HCV RNA at Week 4 of treatment (Arm 1a and Arm 2a). HCV RNA viral load was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan HCV Test v1.0, which has a lower limit of quantification of 43 IU/mL.

Outcome measures

Outcome measures
Measure	Arm 1: Peg-IFN + RBV n=108 Participants Participants received an initial 4 week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, participants with undetectable HCV RNA received open label peg-IFN + RBV for an additional 18 weeks (total of 24 weeks of peg-IFN/RBV therapy) \[Arm 1a\]. Participants with detectable HCV RNA at Week 4 had BOC added to the peg-IFN + RBV regimen at Week 6 and then followed the Response Guided Therapy (RGT) regimen for BOC + peg-IFN + RBV \[Arm 1b\].	Arm 2: BOC + Peg-IFN + RBV n=107 Participants Participants received an initial 4-week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, all participants had BOC added to the peg-IFN + RBV regimen at Week 6 regardless of HCV RNA levels. Participants who had undetectable HCV RNA at Week 4 continued on the BOC + peg-IFN + RBV regimen for an additional 20 weeks (total of 24 weeks of BOC + peg-IFN + RBV therapy) \[Arm 2a\]. Participants with detectable HCV RNA at Week 4 followed the RGT regimen for BOC + peg-IFN + RBV \[Arm 2b\].
Percentage of Participants Who Had Undetectable HCV RNA at Week 4 Achieving SVR24	87.0 Percentage of participants	97.2 Percentage of participants

Adverse Events

Arm 1: Peg-IFN + RBV

Serious events: 27 serious events

Other events: 348 other events

Deaths: 0 deaths

Arm 2: BOC + Peg-IFN + RBV

Serious events: 37 serious events

Other events: 351 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees not to publish or publicly present any interim results of the trial without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Arm 1: Peg-IFN + RBV n=368 participants at risk Participants received an initial 4 week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, participants with undetectable HCV RNA received open label peg-IFN + RBV for an additional 18 weeks (total of 24 weeks of peg-IFN/RBV therapy) \[Arm 1a\]. Participants with detectable HCV RNA at Week 4 had BOC added to the peg-IFN + RBV regimen at Week 6 and then followed the Response Guided Therapy (RGT) regimen for BOC + peg-IFN + RBV \[Arm 1b\].	Arm 2: BOC + Peg-IFN + RBV n=369 participants at risk Participants received an initial 4-week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, all participants had BOC added to the peg-IFN + RBV regimen at Week 6 regardless of HCV RNA levels. Participants who had undetectable HCV RNA at Week 4 continued on the BOC + peg-IFN + RBV regimen for an additional 20 weeks (total of 24 weeks of BOC + peg-IFN + RBV therapy) \[Arm 2a\]. Participants with detectable HCV RNA at Week 4 followed the RGT regimen for BOC + peg-IFN + RBV \[Arm 2b\].
Blood and lymphatic system disorders Neutropenia	0.82% 3/368 • Number of events 4 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Pancytopenia	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Cardiac disorders Atrioventricular block first degree	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Endocrine disorders Autoimmune thyroiditis	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Endocrine disorders Hyperthyroidism	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Anaemia	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.54% 2/369 • Number of events 3 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Gastric ulcer	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Haemorrhoids	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Inflammatory bowel disease	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Oral pain	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Pancreatitis	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 2 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
General disorders Malaise	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
General disorders Pyrexia	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.54% 2/369 • Number of events 2 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis chronic	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Bronchitis viral	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Gastroenteritis	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.54% 2/369 • Number of events 2 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Gastrointestinal infection	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Herpes pharyngitis	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Lobar pneumonia	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Perineal abscess	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Peritonsillar abscess	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Pneumonia	1.1% 4/368 • Number of events 4 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.81% 3/369 • Number of events 3 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Pulmonary tuberculosis	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Pyelonephritis acute	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.54% 2/369 • Number of events 2 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Pyelonephritis chronic	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Salmonellosis	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Tooth infection	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	0.27% 1/368 • Number of events 2 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Alcohol poisoning	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Concussion	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/368 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.27% 1/369 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Ligament sprain	0.27% 1/368 • Number of events 1 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	0.00% 0/369 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.

Other adverse events
Measure	Arm 1: Peg-IFN + RBV n=368 participants at risk Participants received an initial 4 week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, participants with undetectable HCV RNA received open label peg-IFN + RBV for an additional 18 weeks (total of 24 weeks of peg-IFN/RBV therapy) \[Arm 1a\]. Participants with detectable HCV RNA at Week 4 had BOC added to the peg-IFN + RBV regimen at Week 6 and then followed the Response Guided Therapy (RGT) regimen for BOC + peg-IFN + RBV \[Arm 1b\].	Arm 2: BOC + Peg-IFN + RBV n=369 participants at risk Participants received an initial 4-week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, all participants had BOC added to the peg-IFN + RBV regimen at Week 6 regardless of HCV RNA levels. Participants who had undetectable HCV RNA at Week 4 continued on the BOC + peg-IFN + RBV regimen for an additional 20 weeks (total of 24 weeks of BOC + peg-IFN + RBV therapy) \[Arm 2a\]. Participants with detectable HCV RNA at Week 4 followed the RGT regimen for BOC + peg-IFN + RBV \[Arm 2b\].
Blood and lymphatic system disorders Anaemia	45.9% 169/368 • Number of events 219 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	45.5% 168/369 • Number of events 210 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukopenia	10.6% 39/368 • Number of events 66 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	8.9% 33/369 • Number of events 46 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	29.6% 109/368 • Number of events 194 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	29.3% 108/369 • Number of events 161 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	5.2% 19/368 • Number of events 24 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	6.5% 24/369 • Number of events 28 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	4.9% 18/368 • Number of events 18 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	6.0% 22/369 • Number of events 26 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	6.0% 22/368 • Number of events 26 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	3.8% 14/369 • Number of events 18 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	16.8% 62/368 • Number of events 77 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	13.3% 49/369 • Number of events 55 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Dry mouth	6.8% 25/368 • Number of events 26 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	7.0% 26/369 • Number of events 28 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	6.2% 23/368 • Number of events 25 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	9.5% 35/369 • Number of events 39 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	27.2% 100/368 • Number of events 117 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	25.5% 94/369 • Number of events 112 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	12.5% 46/368 • Number of events 68 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	14.4% 53/369 • Number of events 78 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
General disorders Asthenia	22.3% 82/368 • Number of events 108 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	20.1% 74/369 • Number of events 90 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
General disorders Chills	9.8% 36/368 • Number of events 39 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	7.0% 26/369 • Number of events 32 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
General disorders Fatigue	32.1% 118/368 • Number of events 135 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	31.7% 117/369 • Number of events 154 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
General disorders Influenza like illness	9.2% 34/368 • Number of events 39 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	9.5% 35/369 • Number of events 48 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
General disorders Pyrexia	27.4% 101/368 • Number of events 148 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	40.1% 148/369 • Number of events 243 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Investigations Haemoglobin decreased	6.5% 24/368 • Number of events 29 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	8.4% 31/369 • Number of events 33 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	6.5% 24/368 • Number of events 30 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	7.9% 29/369 • Number of events 41 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	14.7% 54/368 • Number of events 60 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	14.4% 53/369 • Number of events 55 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	12.0% 44/368 • Number of events 49 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	12.2% 45/369 • Number of events 52 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	16.6% 61/368 • Number of events 79 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	15.7% 58/369 • Number of events 74 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Nervous system disorders Dizziness	12.5% 46/368 • Number of events 51 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	11.4% 42/369 • Number of events 48 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	17.7% 65/368 • Number of events 69 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	25.5% 94/369 • Number of events 95 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Nervous system disorders Headache	32.1% 118/368 • Number of events 152 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	27.1% 100/369 • Number of events 148 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	7.1% 26/368 • Number of events 29 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	3.8% 14/369 • Number of events 14 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Psychiatric disorders Depression	7.9% 29/368 • Number of events 38 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	5.4% 20/369 • Number of events 22 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	19.0% 70/368 • Number of events 73 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	14.4% 53/369 • Number of events 57 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Psychiatric disorders Irritability	10.3% 38/368 • Number of events 43 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	7.6% 28/369 • Number of events 28 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	17.9% 66/368 • Number of events 83 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	14.1% 52/369 • Number of events 56 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.2% 34/368 • Number of events 36 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	9.2% 34/369 • Number of events 38 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.0% 11/368 • Number of events 13 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	5.4% 20/369 • Number of events 22 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	19.6% 72/368 • Number of events 76 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	19.0% 70/369 • Number of events 74 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dry skin	12.0% 44/368 • Number of events 45 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	11.1% 41/369 • Number of events 41 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	20.4% 75/368 • Number of events 85 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	20.9% 77/369 • Number of events 84 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	18.8% 69/368 • Number of events 82 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.	18.2% 67/369 • Number of events 85 • Up to 78 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All Participants as Treated (APaT) population includes all participants who received at least one dose of study drug.