Trial Outcomes & Findings for A Safety and Efficacy Study of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects Participating in an Intensive Behavior Modification Program (NCT NCT00456521)

NCT ID: NCT00456521

Last Updated: 2014-12-17

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

793 participants

Primary outcome timeframe

Baseline, 56 weeks

Results posted on

2014-12-17

Participant Flow

Participant milestones

Participant milestones
Measure	NB32 Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo Placebo
Overall Study STARTED	591	202
Overall Study COMPLETED	342	118
Overall Study NOT COMPLETED	249	84

Reasons for withdrawal

Reasons for withdrawal
Measure	NB32 Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo Placebo
Overall Study Adverse Event	150	25
Overall Study Withdrawal by Subject	43	24
Overall Study Lost to Follow-up	22	17
Overall Study Lack of Efficacy	3	6
Overall Study Protocol Violation	4	0
Overall Study Pregnancy	1	1
Overall Study Drug non-compliance, moved, other	26	11

Baseline Characteristics

A Safety and Efficacy Study of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects Participating in an Intensive Behavior Modification Program

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NB32 n=591 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=202 Participants Placebo	Total n=793 Participants Total of all reporting groups
Age, Continuous	45.89 years STANDARD_DEVIATION 10.42 • n=5 Participants	45.59 years STANDARD_DEVIATION 11.35 • n=7 Participants	45.82 years STANDARD_DEVIATION 10.66 • n=5 Participants
Sex: Female, Male Female	528 Participants n=5 Participants	185 Participants n=7 Participants	713 Participants n=5 Participants
Sex: Female, Male Male	63 Participants n=5 Participants	17 Participants n=7 Participants	80 Participants n=5 Participants
Race/Ethnicity, Customized White	405 participants n=5 Participants	149 participants n=7 Participants	554 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	145 participants n=5 Participants	44 participants n=7 Participants	189 participants n=5 Participants
Race/Ethnicity, Customized Asian	6 participants n=5 Participants	2 participants n=7 Participants	8 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	7 participants n=5 Participants	1 participants n=7 Participants	8 participants n=5 Participants
Race/Ethnicity, Customized Other	27 participants n=5 Participants	6 participants n=7 Participants	33 participants n=5 Participants
Weight	100.16 kg STANDARD_DEVIATION 15.42 • n=5 Participants	101.88 kg STANDARD_DEVIATION 14.96 • n=7 Participants	100.60 kg STANDARD_DEVIATION 15.31 • n=5 Participants
BMI	36.34 kg/m^2 STANDARD_DEVIATION 4.16 • n=5 Participants	36.96 kg/m^2 STANDARD_DEVIATION 4.18 • n=7 Participants	36.50 kg/m^2 STANDARD_DEVIATION 4.17 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT (Full Analysis Set): Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Outcome measures
Measure	NB32 n=482 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=193 Participants Placebo
Co-primary: Body Weight- Mean Percent Change	-9.29 percentage of body weight Standard Error 0.40	-5.08 percentage of body weight Standard Error 0.60

PRIMARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Outcome measures
Measure	NB32 n=482 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=193 Participants Placebo
Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease	66.39 percentage of participants Interval 62.17 to 70.61	42.49 percentage of participants Interval 35.51 to 49.46

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Outcome measures

Outcome measures
Measure	NB32 n=482 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=193 Participants Placebo
Body Weight- Proportion of Subjects With ≥10% Decrease	41.49 percentage of participants Interval 37.1 to 45.89	20.21 percentage of participants Interval 14.54 to 25.87

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Outcome measures

Outcome measures
Measure	NB32 n=391 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=141 Participants Placebo
Change in Waist Circumference	-9.98 cm Standard Error 0.48	-6.77 cm Standard Error 0.75

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Outcome measures

Outcome measures
Measure	NB32 n=392 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=144 Participants Placebo
Change in Fasting Triglycerides Levels, Using Log-transformed Data	-16.62 percent change Interval -19.66 to -13.47	-8.51 percent change Interval -13.67 to -3.03

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Outcome measures

Outcome measures
Measure	NB32 n=386 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=144 Participants Placebo
Change in Fasting Insulin Levels, Using Log-transformed Data	-27.98 percent change Interval -32.36 to -23.31	-15.45 percent change Interval -23.29 to -6.81

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Outcome measures

Outcome measures
Measure	NB32 n=392 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=144 Participants Placebo
Change in Fasting HDL Cholesterol Levels	4.10 mg/dL Standard Error 0.51	0.87 mg/dL Standard Error 0.80

SECONDARY outcome

Timeframe: Baseline, 56 weeks

IWQOL-Lite= Impact of Weight on Quality of Life-Lite Questionnaire Total score is based on a scale from 0 to 100, with 0 representing the poorest and 100 the best quality of life and where a score of 71-79 indicates moderate impairment

Outcome measures

Outcome measures
Measure	NB32 n=448 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=178 Participants Placebo
Change in IWQOL-Lite Total Scores	13.43 units on a scale Standard Error 0.56	10.29 units on a scale Standard Error 0.86

SECONDARY outcome

Timeframe: Baseline, 56 weeks

HOMA-IR= Homeostasis Model Assessment-Insulin Resistance

Outcome measures

Outcome measures
Measure	NB32 n=385 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=143 Participants Placebo
Change in HOMA-IR Levels, Using Log-transformed Data	-29.93 percent change Interval -34.59 to -24.93	-16.56 percent change Interval -25.02 to -7.14

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Outcome measures

Outcome measures
Measure	NB32 n=386 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=143 Participants Placebo
Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data	-25.87 percent change Interval -32.58 to -18.49	-16.89 percent change Interval -28.31 to -3.66

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Outcome measures

Outcome measures
Measure	NB32 n=393 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=144 Participants Placebo
Change in Fasting Blood Glucose Levels	-2.36 mg/dL Standard Error 0.62	-1.08 mg/dL Standard Error 0.96

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Outcome measures

Outcome measures
Measure	NB32 n=392 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=143 Participants Placebo
Change in Fasting LDL Cholesterol	5.43 mg/dL Standard Error 1.36	8.13 mg/dL Standard Error 2.13

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Outcome measures

Outcome measures
Measure	NB32 n=482 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=193 Participants Placebo
Change in Systolic Blood Pressure	-1.32 mmHg Standard Error 0.47	-3.87 mmHg Standard Error 0.71

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Outcome measures

Outcome measures
Measure	NB32 n=482 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=193 Participants Placebo
Change in Diastolic Blood Pressure	-1.41 mmHg Standard Error 0.33	-2.78 mmHg Standard Error 0.50

SECONDARY outcome

Timeframe: Baseline, 56 weeks

IDS-SR= Inventory of Depressive Symptoms-Subject Rated IDS-SR total score is based on 30 items. The total score can range from 0-84, with 0 being no depressive symptoms and 84 being very severe depressive symptoms. A total score ≤ 13 indicates no depression.

Outcome measures

Outcome measures
Measure	NB32 n=482 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=193 Participants Placebo
Change in IDS-SR Total Scores	0.09 units on a scale Standard Error 0.23	-0.00 units on a scale Standard Error 0.35

SECONDARY outcome

Timeframe: Baseline, 56 weeks

The Food Craving Inventory is a 33-item self-report measure designed to assess specific food cravings and is organized into 4 subscales (high fats, sweets, carbohydrates/starches, and fast-food fats). A craving was defined as an intense desire to consume a particular food (or food type) that was difficult to resist over the past month. Subjects rated their frequency of cravings for each of the 33 items using a 5-point scale, where 1=never, 2=rarely, 3=sometimes, 4=often, and 5=always. The sweets subscale consisted of 8 items and the score ranges from 8 (better outcome) to 40 (worse outcome).

Outcome measures

Outcome measures
Measure	NB32 n=448 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=180 Participants Placebo
Change in Food Craving Inventory Sweets Subscale Scores	-2.54 units on a scale Standard Error 0.22	-2.43 units on a scale Standard Error 0.33

SECONDARY outcome

Timeframe: Baseline, 56 weeks

The Food Craving Inventory is a 33-item self-report measure designed to assess specific food cravings and is organized into 4 subscales (high fats, sweets, carbohydrates/starches, and fast-food fats). A craving was defined as an intense desire to consume a particular food (or food type) that was difficult to resist over the past month. Subjects rated their frequency of cravings for each of the 33 items using a 5-point scale, where 1=never, 2=rarely, 3=sometimes, 4=often, and 5=always. The carbohydrates subscale consisted of 8 items and the score ranges from 8 (better outcome) to 40 (worse outcome).

Outcome measures

Outcome measures
Measure	NB32 n=448 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=180 Participants Placebo
Change in Food Craving Inventory Carbohydrates Subscale Scores	-2.06 units on a scale Standard Error 0.20	-1.97 units on a scale Standard Error 0.31

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Question 19: Generally, how difficult has it been to control your eating? Scoring: 0=not at all difficult; 100=extremely difficult

Outcome measures

Outcome measures
Measure	NB32 n=436 Participants Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=178 Participants Placebo
Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire	-13.75 units on a scale Standard Error 1.17	-8.46 units on a scale Standard Error 1.75

Adverse Events

NB32

Serious events: 22 serious events

Other events: 465 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 132 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Head of Global Development

Orexigen Therapeutics, Inc.

Phone: (858) 875-8600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If not already published by Sponsor as part of a multi-center publication, 18 months after conclusion of the study at all study centers, PI may publish the results for PI's study center individually. Prior to such publication, PI must provide Sponsor with at least 60 days to review and comment on the proposed publication. The review period may be extended by an additional 30 days upon request. Sponsor may delay publication for up to an additional 6 month period to file for patent protection.
Publication restrictions are in place

Restriction type: OTHER

Measure	NB32 n=584 participants at risk Naltrexone SR 32 mg/ bupropion SR 360 mg/ day	Placebo n=200 participants at risk Placebo
Ear and labyrinth disorders Tinnitus	5.3% 31/584 • Number of events 33 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	0.50% 1/200 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Gastrointestinal disorders Abdominal pain upper	5.5% 32/584 • Number of events 33 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	1.5% 3/200 • Number of events 4 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Gastrointestinal disorders Constipation	24.1% 141/584 • Number of events 157 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	14.0% 28/200 • Number of events 32 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Gastrointestinal disorders Diarrhoea	7.4% 43/584 • Number of events 45 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	7.5% 15/200 • Number of events 16 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Gastrointestinal disorders Dry mouth	8.0% 47/584 • Number of events 48 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	3.0% 6/200 • Number of events 6 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Gastrointestinal disorders Nausea	34.1% 199/584 • Number of events 228 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	10.5% 21/200 • Number of events 21 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Gastrointestinal disorders Vomiting	11.0% 64/584 • Number of events 76 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	6.5% 13/200 • Number of events 13 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
General disorders Fatigue	5.3% 31/584 • Number of events 35 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	6.5% 13/200 • Number of events 13 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Infections and infestations Nasopharyngitis	6.2% 36/584 • Number of events 41 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	7.5% 15/200 • Number of events 18 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Infections and infestations Upper respiratory tract infection	6.5% 38/584 • Number of events 40 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	9.0% 18/200 • Number of events 19 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Musculoskeletal and connective tissue disorders Back pain	4.8% 28/584 • Number of events 33 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	6.0% 12/200 • Number of events 12 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Nervous system disorders Dizziness	14.6% 85/584 • Number of events 96 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	4.5% 9/200 • Number of events 10 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Nervous system disorders Headache	23.8% 139/584 • Number of events 167 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	17.5% 35/200 • Number of events 42 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Nervous system disorders Tremor	5.8% 34/584 • Number of events 41 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	1.0% 2/200 • Number of events 2 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Psychiatric disorders Anxiety	5.1% 30/584 • Number of events 34 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	3.5% 7/200 • Number of events 7 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Psychiatric disorders Insomnia	8.7% 51/584 • Number of events 51 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	6.0% 12/200 • Number of events 13 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Respiratory, thoracic and mediastinal disorders Cough	4.8% 28/584 • Number of events 35 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	7.5% 15/200 • Number of events 18 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.4% 20/584 • Number of events 23 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	5.0% 10/200 • Number of events 12 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	5.0% 29/584 • Number of events 36 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	8.5% 17/200 • Number of events 19 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.
Respiratory, thoracic and mediastinal disorders Sinus congestion	3.1% 18/584 • Number of events 20 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.	6.5% 13/200 • Number of events 15 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study.Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 30 days post last dose.