Trial Outcomes & Findings for Study of Efficacy and Safety of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in Chronic Hepatitis C Participants With Child-Pugh (CP)-B Hepatic Insufficiency (MK-5172-059) (NCT NCT02115321)

Last Updated: 2019-06-26

Results Overview

SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels below the lower limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

40 participants

Primary outcome timeframe

Week 24

Results posted on

2019-06-26

Participant Flow

The screening period lasted for 60 days. Recruitment was halted after enrolling participants in the two Part A arms, as the current clinical development plan is focused on a fixed-dose combination (FDC) product containing grazoprevir (GZR) 100 mg and elbasvir (EBR) 50 mg. No participants were enrolled in Parts B or C.

Participant milestones

Participant milestones
Measure	Part A: CP-B GZR 50 mg + EBR 50 mg Child-Pugh score 7 to 9 (CP-B) participants take GZR 50 mg + EBR 50 mg once daily (q.d.) by mouth for 12 weeks.	Part A: NC GZR 100 mg + EBR 50 mg Non-cirrhotic (NC) participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Overall Study STARTED	30	10
Overall Study COMPLETED	29	10
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: CP-B GZR 50 mg + EBR 50 mg Child-Pugh score 7 to 9 (CP-B) participants take GZR 50 mg + EBR 50 mg once daily (q.d.) by mouth for 12 weeks.	Part A: NC GZR 100 mg + EBR 50 mg Non-cirrhotic (NC) participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Overall Study Death	1	0

Baseline Characteristics

Study of Efficacy and Safety of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in Chronic Hepatitis C Participants With Child-Pugh (CP)-B Hepatic Insufficiency (MK-5172-059)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: CP-B GZR 50 mg + EBR 50 mg n=30 Participants CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Part A: NC GZR 100 mg + ER 50 mg n=10 Participants NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Total n=40 Participants Total of all reporting groups
Age, Continuous	58.3 Years STANDARD_DEVIATION 7.0 • n=99 Participants	60.4 Years STANDARD_DEVIATION 5.3 • n=107 Participants	58.8 Years STANDARD_DEVIATION 6.6 • n=206 Participants
Sex: Female, Male Female	13 Participants n=99 Participants	5 Participants n=107 Participants	18 Participants n=206 Participants
Sex: Female, Male Male	17 Participants n=99 Participants	5 Participants n=107 Participants	22 Participants n=206 Participants

PRIMARY outcome

Timeframe: Week 24

Population: The Full Analysis Set (FAS) consists of all randomized participants who received at least one dose of study medication.

Outcome measures

Outcome measures
Measure	Part A: NC GZR 100 mg + ER 50 mg n=10 Participants NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Part A: CP-B GZR 50 mg + EBR 50 mg n=30 Participants CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Percentage of Participants Achieving Sustained Viral Response 12 Weeks After Completing Study Therapy (SVR12)	100.0 Percentage of participants Interval 69.2 to 100.0	90.0 Percentage of participants Interval 73.5 to 97.9

PRIMARY outcome

Timeframe: Up to 14 weeks

Population: The All Participants as Treated (APaT) population consisted of all randomized participants who received at least one dose of study medication.

An 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.

Outcome measures

Outcome measures
Measure	Part A: NC GZR 100 mg + ER 50 mg n=10 Participants NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Part A: CP-B GZR 50 mg + EBR 50 mg n=30 Participants CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Number of Participants Experiencing an Adverse Event (AE) During Treatment and First 14 Follow-up Days	8 Number of participants	25 Number of participants

PRIMARY outcome

Timeframe: Up to 12 weeks

Population: The APaT population consisted of all randomized participants who received at least one dose of study medication.

An 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.

Outcome measures

Outcome measures
Measure	Part A: NC GZR 100 mg + ER 50 mg n=10 Participants NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Part A: CP-B GZR 50 mg + EBR 50 mg n=30 Participants CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Number of Participants Discontinuing Study Drug Due to an AE	0 Number of participants	0 Number of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, and 36

Population: All CP-B participants in the FAS (all randomized participants who received at least one dose of study medication) with available data.

The MELD score provides an objective and granular assessment of liver improvement as a continuous variable. The calculation of MELD score is based on three biochemical variables (serum bilirubin, creatinine and international normalized ratio \[INR\] of prothrombin time). The MELD equation is as follows: 9.57 x ln(creatinine mg/dL) +3.78 x ln(bilirubin mg/dL) +11.2 x ln (INR) + 6.43. Scores are multiplied by 10 and rounded to the nearest whole number and range from 6 (less ill) to 40 (gravely ill). MELD scores were determined at Baseline (Day 1) and again at Week 12, Follow-up (FU) Week 12 (Week 24), and FU Week 24 (Week 36). Change from baseline in MELD score = Post-baseline MELD score - baseline MELD score.

Outcome measures

Outcome measures
Measure	Part A: NC GZR 100 mg + ER 50 mg NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Part A: CP-B GZR 50 mg + EBR 50 mg n=30 Participants CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores in CP-B Participants Week 12 (n=30)	—	-0.67 Units on a scale Standard Deviation 1.35
Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores in CP-B Participants FU Week 12 (Week 24) [n=29]	—	-0.38 Units on a scale Standard Deviation 1.74
Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores in CP-B Participants FU Week 24 (Week 36) [n=29]	—	-0.34 Units on a scale Standard Deviation 3.15

SECONDARY outcome

Timeframe: Week 2, 4, and 12

Population: Per protocol, this measure was to be determined in Arm 4 (Part C); however, enrollment was halted after Part A and thus no data are available.

HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2, 4, and 12

Population: Per protocol, this measure was to be determined in Arm 4 (Part C); however, enrollment was halted after Part A and thus no data are available.

HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 16

Population: The FAS consists of all randomized participants who received at least one dose of study medication.

SVR4 was defined as HCV RNA levels \<LLoQ 4 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

Outcome measures

Outcome measures
Measure	Part A: NC GZR 100 mg + ER 50 mg n=10 Participants NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Part A: CP-B GZR 50 mg + EBR 50 mg n=30 Participants CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Percentage of Participants Achieving Sustained Viral Response 4 Weeks After Completing Study Therapy (SVR4)	100.0 Percentage of participants Interval 69.2 to 100.0	93.3 Percentage of participants Interval 77.9 to 99.2

SECONDARY outcome

Timeframe: Week 36

Population: The FAS consists of all randomized participants who received at least one dose of study medication.

SVR24 was defined as HCV RNA levels \<LLoQ 24 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

Outcome measures

Outcome measures
Measure	Part A: NC GZR 100 mg + ER 50 mg n=10 Participants NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Part A: CP-B GZR 50 mg + EBR 50 mg n=30 Participants CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Percentage of Participants Achieving Sustained Viral Response 24 Weeks After Completing Study Therapy (SVR24)	100.0 Percentage of participants Interval 69.2 to 100.0	90.0 Percentage of participants Interval 73.5 to 97.9

Adverse Events

CP-B: GZR 50 mg + EBR 50 mg for 12 Weeks

Serious events: 5 serious events

Other events: 20 other events

Deaths: 0 deaths

Non-cirrhotic: GZR 100 mg + EBR 50 mg for 12 Weeks

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CP-B: GZR 50 mg + EBR 50 mg for 12 Weeks n=30 participants at risk CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Non-cirrhotic: GZR 100 mg + EBR 50 mg for 12 Weeks n=10 participants at risk NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Gastrointestinal disorders Ascites	3.3% 1/30 • Number of events 1 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Infections and infestations Peritonitis bacterial	3.3% 1/30 • Number of events 2 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Nervous system disorders Cerebral infarction	3.3% 1/30 • Number of events 1 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Blood and lymphatic system disorders Anaemia	3.3% 1/30 • Number of events 1 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Gastrointestinal disorders Varices oesophageal	3.3% 1/30 • Number of events 1 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Hepatobiliary disorders Hepatic failure	3.3% 1/30 • Number of events 1 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Metabolism and nutrition disorders Malnutrition	3.3% 1/30 • Number of events 1 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	3.3% 1/30 • Number of events 1 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Nervous system disorders Encephalopathy	3.3% 1/30 • Number of events 1 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.

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 Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation.
Publication restrictions are in place

Restriction type: OTHER

Measure	CP-B: GZR 50 mg + EBR 50 mg for 12 Weeks n=30 participants at risk CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Non-cirrhotic: GZR 100 mg + EBR 50 mg for 12 Weeks n=10 participants at risk NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Blood and lymphatic system disorders Increased tendency to bruise	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Ear and labyrinth disorders Ear discomfort	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Eye disorders Retinal detachment	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Gastrointestinal disorders Abdominal discomfort	3.3% 1/30 • Number of events 1 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Gastrointestinal disorders Abdominal pain	6.7% 2/30 • Number of events 2 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Gastrointestinal disorders Diarrhoea	6.7% 2/30 • Number of events 2 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Gastrointestinal disorders Nausea	10.0% 3/30 • Number of events 3 • Up to 36 weeks. An 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.	20.0% 2/10 • Number of events 2 • Up to 36 weeks. An 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.
Gastrointestinal disorders Vomiting	6.7% 2/30 • Number of events 2 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
General disorders Chills	6.7% 2/30 • Number of events 2 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
General disorders Fatigue	30.0% 9/30 • Number of events 11 • Up to 36 weeks. An 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.	30.0% 3/10 • Number of events 3 • Up to 36 weeks. An 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.
General disorders Feeling abnormal	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
General disorders Pyrexia	10.0% 3/30 • Number of events 3 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Infections and infestations Influenza	10.0% 3/30 • Number of events 3 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Infections and infestations Tooth infection	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Infections and infestations Urinary tract infection	10.0% 3/30 • Number of events 3 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Investigations Blood creatine phosphokinase increased	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 5/30 • Number of events 5 • Up to 36 weeks. An 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.	20.0% 2/10 • Number of events 3 • Up to 36 weeks. An 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.
Musculoskeletal and connective tissue disorders Myalgia	6.7% 2/30 • Number of events 2 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Nervous system disorders Dizziness	6.7% 2/30 • Number of events 2 • Up to 36 weeks. An 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.	0.00% 0/10 • Up to 36 weeks. An 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.
Nervous system disorders Headache	10.0% 3/30 • Number of events 3 • Up to 36 weeks. An 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.	50.0% 5/10 • Number of events 6 • Up to 36 weeks. An 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.
Nervous system disorders Sinus headache	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Psychiatric disorders Affect lability	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Psychiatric disorders Insomnia	6.7% 2/30 • Number of events 2 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Respiratory, thoracic and mediastinal disorders Cough	6.7% 2/30 • Number of events 2 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Skin and subcutaneous tissue disorders Acne	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Gastrointestinal disorders Constipation	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.
Infections and infestations Pneumonia	0.00% 0/30 • Up to 36 weeks. An 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.	10.0% 1/10 • Number of events 1 • Up to 36 weeks. An 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.