Trial Outcomes & Findings for Study to Evaluate the Safety and Efficacy of Stribild Versus Atripla in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults (NCT NCT01095796)

NCT ID: NCT01095796

Last Updated: 2015-11-11

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

707 participants

Primary outcome timeframe

Week 48

Results posted on

2015-11-11

Participant Flow

Participants were enrolled at sites in the United States and Puerto Rico. The first participant was screened on 16 March 2010. The last study visit occurred on 02 September 2014.

917 participants were screened.

Participant milestones

Participant milestones
Measure	Stribild Stribild® (elvitegravir (EVG) 150 mg/cobicistat (COBI) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg) single-tablet regimen (STR) once daily plus placebo to match Atripla once daily prior to bedtime	Atripla Atripla® (efavirenz (EFV) 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily
Overall Study STARTED	353	354
Overall Study COMPLETED	58	65
Overall Study NOT COMPLETED	295	289

Reasons for withdrawal

Reasons for withdrawal
Measure	Stribild Stribild® (elvitegravir (EVG) 150 mg/cobicistat (COBI) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg) single-tablet regimen (STR) once daily plus placebo to match Atripla once daily prior to bedtime	Atripla Atripla® (efavirenz (EFV) 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily
Overall Study Randomized but Not Treated	5	2
Overall Study Adverse Event	9	19
Overall Study Death	3	2
Overall Study Pregnancy	2	0
Overall Study Lack of Efficacy	5	3
Overall Study Investigator's Discretion	7	2
Overall Study Withdrew Consent	16	22
Overall Study Lost to Follow-up	27	29
Overall Study Participant Noncompliance	5	10
Overall Study Protocol Violation	1	0
Overall Study Participant Transferred to Another Study	215	200

Baseline Characteristics

Study to Evaluate the Safety and Efficacy of Stribild Versus Atripla in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stribild n=348 Participants Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime	Atripla n=352 Participants Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily	Total n=700 Participants Total of all reporting groups
Age, Continuous	38 years STANDARD_DEVIATION 10.4 • n=5 Participants	38 years STANDARD_DEVIATION 10.6 • n=7 Participants	38 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	36 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Male	307 Participants n=5 Participants	316 Participants n=7 Participants	623 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized Asian	6 participants n=5 Participants	10 participants n=7 Participants	16 participants n=5 Participants
Race/Ethnicity, Customized Black or African Heritage	106 participants n=5 Participants	91 participants n=7 Participants	197 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized White	214 participants n=5 Participants	227 participants n=7 Participants	441 participants n=5 Participants
Race/Ethnicity, Customized Other	16 participants n=5 Participants	19 participants n=7 Participants	35 participants n=5 Participants
Region of Enrollment United States	348 participants n=5 Participants	352 participants n=7 Participants	700 participants n=5 Participants
HIV Disease Status Asymptomatic	290 participants n=5 Participants	295 participants n=7 Participants	585 participants n=5 Participants
HIV Disease Status Symptomatic HIV Infections	30 participants n=5 Participants	33 participants n=7 Participants	63 participants n=5 Participants
HIV Disease Status AIDS	28 participants n=5 Participants	24 participants n=7 Participants	52 participants n=5 Participants
Hepatitis B Virus (HBV) Infection Status Negative	343 participants n=5 Participants	343 participants n=7 Participants	686 participants n=5 Participants
Hepatitis B Virus (HBV) Infection Status Positive	5 participants n=5 Participants	9 participants n=7 Participants	14 participants n=5 Participants
Hepatitis C Virus (HCV) Infection Status Negative	331 participants n=5 Participants	337 participants n=7 Participants	668 participants n=5 Participants
Hepatitis C Virus (HCV) Infection Status Positive	17 participants n=5 Participants	15 participants n=7 Participants	32 participants n=5 Participants
HIV-1 RNA Category (copies/mL) ≤ 100,000	230 participants n=5 Participants	236 participants n=7 Participants	466 participants n=5 Participants
HIV-1 RNA Category (copies/mL) > 100,000	118 participants n=5 Participants	116 participants n=7 Participants	234 participants n=5 Participants
CD4 Cell Count (/µL) ≤ 50	7 participants n=5 Participants	6 participants n=7 Participants	13 participants n=5 Participants
CD4 Cell Count (/µL) 51 to ≤ 200	36 participants n=5 Participants	45 participants n=7 Participants	81 participants n=5 Participants
CD4 Cell Count (/µL) 201 to ≤ 350	112 participants n=5 Participants	96 participants n=7 Participants	208 participants n=5 Participants
CD4 Cell Count (/µL) 351 to ≤ 500	113 participants n=5 Participants	136 participants n=7 Participants	249 participants n=5 Participants
CD4 Cell Count (/µL) > 500	80 participants n=5 Participants	69 participants n=7 Participants	149 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: Intent-to-treat (ITT) Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	Stribild n=348 Participants Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime	Atripla n=352 Participants Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily
The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48	87.6 percentage of participants	84.1 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: ITT Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	Stribild n=348 Participants Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime	Atripla n=352 Participants Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily
The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96	84.2 percentage of participants	81.5 percentage of participants

SECONDARY outcome

Timeframe: Week 144

Population: ITT Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	Stribild n=348 Participants Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime	Atripla n=352 Participants Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily
The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144	80.2 percentage of participants	75.3 percentage of participants

SECONDARY outcome

Timeframe: Week 192

Population: Week 192 Modified Intent-to-treat (MITT) Analysis Set: Participants in the ITT analysis set, excluding those who either 1) transferred to other Gilead-sponsored studies after completing their Week 144 Visit and before the lower limit of the Week 192 analysis window, or 2) prematurely discontinued study drug prior to the Week 144 Visit.

Outcome measures

Outcome measures
Measure	Stribild n=71 Participants Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime	Atripla n=73 Participants Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily
The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192	76.1 percentage of participants	78.1 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: ITT Analysis Set

Outcome measures

Outcome measures
Measure	Stribild n=348 Participants Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime	Atripla n=352 Participants Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily
The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm	85.9 percentage of participants	83.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Weeks 48, 96, 144, and 192

Population: ITT Analysis Set. The missing = excluded (M = E) method was used in which all participants with missing data were excluded from analysis.

Change = value of the relevant time point minus the baseline value

Outcome measures

Outcome measures
Measure	Stribild n=348 Participants Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime	Atripla n=352 Participants Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily
The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 Change at Wk 48 (Stribild, n=325; Atripla, n=315)	239 cells/µL Standard Deviation 167.2	206 cells/µL Standard Deviation 153.4
The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 Change at Wk 96 (Stribild, n=307; Atripla, n=302)	295 cells/µL Standard Deviation 213.3	273 cells/µL Standard Deviation 189.7
The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 Change at Wk 144 (Stribild, n=294; Atripla, n=283)	321 cells/µL Standard Deviation 227.0	300 cells/µL Standard Deviation 202.3
The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 Change at Wk 192 (Stribild, n=62; Atripla, n=69)	360 cells/µL Standard Deviation 285.9	328 cells/µL Standard Deviation 227.6

SECONDARY outcome

Timeframe: Week 48

Population: ITT Analysis Set. The missing = failure (M = F) method was used in which all missing data were considered as failure (HIV-1 RNA ≥ 50 copies/mL).

Outcome measures

Outcome measures
Measure	Stribild n=348 Participants Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime	Atripla n=352 Participants Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily
The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48	88.8 percentage of participants	85.5 percentage of participants

Adverse Events

Stribild

Serious events: 69 serious events

Other events: 313 other events

Deaths: 0 deaths

Atripla

Serious events: 50 serious events

Other events: 326 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Disclosures

Gilead Sciences, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Measure	Stribild n=348 participants at risk Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime	Atripla n=352 participants at risk Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily
Blood and lymphatic system disorders Lymphadenopathy	4.6% 16/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	5.1% 18/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	6.9% 24/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	5.1% 18/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Gastrointestinal disorders Constipation	6.3% 22/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	4.0% 14/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	26.7% 93/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	25.9% 91/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	5.5% 19/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	2.8% 10/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.5% 19/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	4.0% 14/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Gastrointestinal disorders Haemorrhoids	6.6% 23/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	3.7% 13/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Gastrointestinal disorders Nausea	23.0% 80/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	16.8% 59/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Gastrointestinal disorders Vomiting	8.0% 28/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	6.5% 23/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
General disorders Fatigue	15.2% 53/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	17.3% 61/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
General disorders Pyrexia	6.0% 21/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	6.5% 23/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Infections and infestations Bronchitis	11.8% 41/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	10.5% 37/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Infections and infestations Chlamydial infection	6.6% 23/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	3.7% 13/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Infections and infestations Folliculitis	4.9% 17/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	5.1% 18/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Infections and infestations Gonorrhoea	6.3% 22/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	2.6% 9/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Infections and infestations Herpes zoster	5.5% 19/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	2.6% 9/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Infections and infestations Influenza	4.3% 15/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	5.4% 19/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Infections and infestations Nasopharyngitis	10.9% 38/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	9.7% 34/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Infections and infestations Pharyngitis	4.6% 16/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	6.2% 22/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Infections and infestations Sinusitis	11.8% 41/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	13.1% 46/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Infections and infestations Syphilis	9.8% 34/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	9.4% 33/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	26.4% 92/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	22.2% 78/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	5.2% 18/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	4.3% 15/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	9.5% 33/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	6.2% 22/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	10.9% 38/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	7.4% 26/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	6.0% 21/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	6.8% 24/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anorectal human papilloma virus infection	5.7% 20/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	3.7% 13/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Nervous system disorders Dizziness	8.3% 29/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	26.7% 94/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Nervous system disorders Headache	17.8% 62/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	12.8% 45/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Nervous system disorders Somnolence	2.0% 7/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	8.0% 28/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Psychiatric disorders Abnormal dreams	16.1% 56/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	28.7% 101/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Psychiatric disorders Anxiety	8.6% 30/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	9.4% 33/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Psychiatric disorders Depression	16.1% 56/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	16.8% 59/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Psychiatric disorders Insomnia	13.5% 47/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	17.9% 63/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Reproductive system and breast disorders Erectile dysfunction	3.7% 13/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	6.0% 21/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	11.2% 39/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	7.4% 26/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.6% 23/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	9.1% 32/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Sinus congestion	6.3% 22/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	4.0% 14/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis	4.6% 16/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	5.7% 20/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	10.1% 35/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	15.1% 53/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Vascular disorders Hypertension	6.0% 21/348 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.	6.2% 22/352 • Up to 218 weeks plus 30 days Safety Analysis Set: participants were randomized and received at least one dose of study drug.