Trial Outcomes & Findings for MGR001 / Advair Diskus Local Equivalence Study in Asthma (NCT NCT02245672)

Last Updated: 2022-02-24

Results Overview

The FEV1 AUEC(0-12) on Day 1 was calculated from FEV1 measurements collected 30 minutes prior to morning dose, 0 minutes prior to morning dose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours following completion of dosing on Day 1 (Visit 3). The baseline for the FEV1 AUEC(0-12) endpoint was the mean of the 2 predose FEV1 measures. To confirm assay sensitivity, both active treatments (MGR001 and Advair Diskus) had to be significantly superior to placebo

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1128 participants

Primary outcome timeframe

0-12 hours after dosing on Day 1

Results posted on

2022-02-24

Participant Flow

Participant milestones

Participant milestones
Measure	MGR001 MGR001 administered two times per day by inhalation throughout the study MGR001 (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the CRC749 inhaler device	Advair Diskus Advair Diskus administered two times per day by inhalation throughout the study Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Diskus inhaler device	Placebo Placebo for Advair Diskus and MGR001 administered two times per day by inhalation throughout the study Placebo: Placebo administered via the CRC749 and Diskus devices
Overall Study STARTED	512	513	103
Overall Study COMPLETED	499	500	98
Overall Study NOT COMPLETED	13	13	5

Reasons for withdrawal

Reasons for withdrawal
Measure	MGR001 MGR001 administered two times per day by inhalation throughout the study MGR001 (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the CRC749 inhaler device	Advair Diskus Advair Diskus administered two times per day by inhalation throughout the study Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Diskus inhaler device	Placebo Placebo for Advair Diskus and MGR001 administered two times per day by inhalation throughout the study Placebo: Placebo administered via the CRC749 and Diskus devices
Overall Study Adverse Event	4	4	4
Overall Study Lost to Follow-up	3	5	1
Overall Study Withdrawal by Subject	6	3	0
Overall Study Randomized in error (not treated)	0	1	0

Baseline Characteristics

MGR001 / Advair Diskus Local Equivalence Study in Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MGR001 n=512 Participants MGR001 administered two times per day by inhalation throughout the study MGR001 (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the CRC749 inhaler device	Advair Diskus n=512 Participants Advair Diskus administered two times per day by inhalation throughout the study Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Diskus inhaler device	Placebo n=103 Participants Placebo for Advair Diskus and MGR001 administered two times per day by inhalation throughout the study Placebo: Placebo administered via the CRC749 and Diskus devices	Total n=1127 Participants Total of all reporting groups
Age, Continuous	42.6 years STANDARD_DEVIATION 14.08 • n=93 Participants	42.5 years STANDARD_DEVIATION 14.21 • n=4 Participants	43.5 years STANDARD_DEVIATION 13.85 • n=27 Participants	42.6 years STANDARD_DEVIATION 14.11 • n=483 Participants
Sex: Female, Male Female	306 Participants n=93 Participants	309 Participants n=4 Participants	64 Participants n=27 Participants	679 Participants n=483 Participants
Sex: Female, Male Male	206 Participants n=93 Participants	203 Participants n=4 Participants	39 Participants n=27 Participants	448 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	102 Participants n=93 Participants	92 Participants n=4 Participants	24 Participants n=27 Participants	218 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	410 Participants n=93 Participants	420 Participants n=4 Participants	79 Participants n=27 Participants	909 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	11 Participants n=93 Participants	11 Participants n=4 Participants	1 Participants n=27 Participants	23 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants
Race (NIH/OMB) Black or African American	92 Participants n=93 Participants	98 Participants n=4 Participants	22 Participants n=27 Participants	212 Participants n=483 Participants
Race (NIH/OMB) White	378 Participants n=93 Participants	372 Participants n=4 Participants	73 Participants n=27 Participants	823 Participants n=483 Participants
Race (NIH/OMB) More than one race	30 Participants n=93 Participants	31 Participants n=4 Participants	6 Participants n=27 Participants	67 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Region of Enrollment United States	512 participants n=93 Participants	512 participants n=4 Participants	103 participants n=27 Participants	1127 participants n=483 Participants
Body Mass Index (BMI)	29.38 kg/m^2 STANDARD_DEVIATION 6.026 • n=93 Participants	29.12 kg/m^2 STANDARD_DEVIATION 5.886 • n=4 Participants	29.37 kg/m^2 STANDARD_DEVIATION 5.890 • n=27 Participants	29.26 kg/m^2 STANDARD_DEVIATION 5.947 • n=483 Participants

PRIMARY outcome

Timeframe: 0-12 hours after dosing on Day 1

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	MGR001 n=508 Participants MGR001 administered two times per day by inhalation throughout the study MGR001 (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the CRC749 inhaler device	Advair Diskus n=510 Participants Advair Diskus administered two times per day by inhalation throughout the study Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Diskus inhaler device	Placebo n=102 Participants Placebo for Advair Diskus and MGR001 administered two times per day by inhalation throughout the study Placebo: Placebo administered via the CRC749 and Diskus devices
Forced Exhaled Volume in 1 Sec (FEV1) Area Under the Effect Curve on Day 1 (Assay Sensitivity)	3.9534 L*hr Standard Error 0.1609	3.4964 L*hr Standard Error 0.1595	0.8191 L*hr Standard Error 0.3477

PRIMARY outcome

Timeframe: 0-12 hours after dosing on Day 1

Population: Per Protocol Set

Outcome measures

Outcome measures
Measure	MGR001 n=497 Participants MGR001 administered two times per day by inhalation throughout the study MGR001 (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the CRC749 inhaler device	Advair Diskus n=494 Participants Advair Diskus administered two times per day by inhalation throughout the study Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Diskus inhaler device	Placebo n=94 Participants Placebo for Advair Diskus and MGR001 administered two times per day by inhalation throughout the study Placebo: Placebo administered via the CRC749 and Diskus devices
Forced Exhaled Volume in 1 Sec (FEV1) Area Under the Effect Curve on Day 1 (Bioequivalence)	3.9734 L*hr Standard Error 0.1704	3.5411 L*hr Standard Error 0.1593	0.8400 L*hr Standard Error 0.2983

PRIMARY outcome

Timeframe: Day 1 and Day 29

Population: Full Analysis Set

Change from baseline in trough (pre-dose) FEV1 at Day 29 was based on 2 pre-dose FEV1 assessments performed 30 minutes apart on Day 29. Baseline was calculated by taking the mean of \[prebronchodilator FEV1 measured at a run-in visit and the mean of 2 predose FEV1 measures taken at Day 1\]. To confirm assay sensitivity, both active treatments (MGR001 and Advair Diskus) had to be significantly superior to placebo.

Outcome measures

Outcome measures
Measure	MGR001 n=504 Participants MGR001 administered two times per day by inhalation throughout the study MGR001 (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the CRC749 inhaler device	Advair Diskus n=505 Participants Advair Diskus administered two times per day by inhalation throughout the study Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Diskus inhaler device	Placebo n=100 Participants Placebo for Advair Diskus and MGR001 administered two times per day by inhalation throughout the study Placebo: Placebo administered via the CRC749 and Diskus devices
FEV1 Trough Value (Assay Sensitivity)	0.2927 L Standard Error 0.0162	0.2720 L Standard Error 0.0161	0.0575 L Standard Error 0.0353

PRIMARY outcome

Timeframe: Day 1 and Day 29

Population: Per Protocol Set

Outcome measures

Outcome measures
Measure	MGR001 n=498 Participants MGR001 administered two times per day by inhalation throughout the study MGR001 (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the CRC749 inhaler device	Advair Diskus n=497 Participants Advair Diskus administered two times per day by inhalation throughout the study Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Diskus inhaler device	Placebo n=99 Participants Placebo for Advair Diskus and MGR001 administered two times per day by inhalation throughout the study Placebo: Placebo administered via the CRC749 and Diskus devices
FEV1 Trough Value (Bioequivalence)	0.2911 L Standard Error 0.0163	0.2728 L Standard Error 0.0162	0.0574 L Standard Error 0.0355

Adverse Events

MGR001

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

Advair Diskus

Serious events: 0 serious events

Other events: 51 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dik Ng, PhD

Mylan Pharma UK Ltd

Phone: +44-7467-941703

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	MGR001 n=512 participants at risk MGR001 administered two times per day by inhalation throughout the study MGR001 (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the CRC749 inhaler device	Advair Diskus n=512 participants at risk Advair Diskus administered two times per day by inhalation throughout the study Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Diskus inhaler device	Placebo n=103 participants at risk Placebo for Advair Diskus and MGR001 administered two times per day by inhalation throughout the study Placebo: Placebo administered via the CRC749 and Diskus devices
Infections and infestations Upper respiratory tract infection	1.4% 7/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	2.1% 11/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.00% 0/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Infections and infestations Nasopharyngitis	0.59% 3/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	1.4% 7/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	1.9% 2/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Infections and infestations Sinusitis	0.59% 3/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.59% 3/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.97% 1/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Infections and infestations Oral candidiasis	0.78% 4/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.39% 2/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.00% 0/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Infections and infestations Urinary tract infection	0.39% 2/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.39% 2/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.00% 0/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Infections and infestations Viral upper respiratory tract	0.20% 1/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.59% 3/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.00% 0/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Infections and infestations Bronchitis	0.39% 2/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.00% 0/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.97% 1/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Infections and infestations Gastroenteritis	0.00% 0/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.59% 3/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.00% 0/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Infections and infestations Viral infection	0.20% 1/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.39% 2/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.00% 0/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Respiratory, thoracic and mediastinal disorders Asthma	1.4% 7/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	2.0% 10/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	4.9% 5/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.59% 3/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.98% 5/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.97% 1/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.20% 1/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.59% 3/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.00% 0/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Respiratory, thoracic and mediastinal disorders Cough	0.20% 1/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.39% 2/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.00% 0/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Gastrointestinal disorders Dyspepsia	0.20% 1/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.39% 2/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.00% 0/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.
Nervous system disorders Headache	0.59% 3/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.98% 5/512 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.	0.00% 0/103 • Adverse events (AEs) were collected from the signing of the ICF but are reported from Day 1 to 30 days after the last dose of double-blind study medication. Subjects were routinely queried for AEs using open-ended questions. Spontaneously reported AEs were also recorded. The most frequent AEs occurring in at least 3 subjects across the 3 treatment groups are reported, equating to 0.2% of subjects in the Safety Set.