Trial Outcomes & Findings for A Study in Asthmatic Patients to Determine if There is Any Difference in Dosing With Fluticasone Furoate/Vilanterol Inhalation Powder in the Morning or Evening on Lung Function (NCT NCT01287065)

Last Updated: 2017-01-11

Results Overview

Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured electronically by spirometry at Day 14. Weighted mean FEV1 was calculated using the Day 14 24-hour serial FEV1 measurements taken at the following time points: pre-dose (Day 14 evening dose), and 3, 6, 9, 12, 15, 18, 21 and 24 hours post-dose (measured in the evening of Day 15). At each time point, the highest of 3 technically acceptable measurements was recorded. The analysis was performed using a mixed effects analysis of covariance model with fixed effect terms for treatment and period; and participant (par.) baseline, period baseline, gender and age fitted as covariates; and par. as a random effect. Par. 122 received FF/VI 100/25 PM in treatment periods 1 and 3 and contributed twice to the summary of FF/VI 100/25 PM (n=25). Par. 123 received Placebo in treatment periods 2 and 3 and contributed twice to the summary of Placebo (n=20).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

Pre-dose on Day 14 to 24 hours post-dose

Results posted on

2017-01-11

Participant Flow

Participant milestones

Participant milestones
Measure	Sequence 1: Placebo, FF/VI 100/25 µg AM, FF/VI 100/25 µg PM Participants received placebo, Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) AM, and FF/VI 100/25 µg PM in Treatment Periods 1, 2, and 3, respectively. Participants received all treatments once a day (OD) in the evening from a Dry Powder Inhaler (DPI) for 14 days. Each 14 day treatment period was followed by a 14-21 day washout period.	Sequence 2: Placebo, FF/VI 100/25 µg PM, FF/VI 100/25 µg AM Participants received placebo, FF/VI 100/25 µg PM, and FF/VI 100/25 µg AM in Treatment Periods 1, 2, and 3, respectively. Participants received all treatments once a day in the evening from a DPI for 14 days. Each 14 day treatment period was followed by a 14-21 day washout period.	Sequence 3: FF/VI 100/25 µg AM, FF/VI 100/25 µg PM, Placebo Participants received FF/VI 100/25 µg AM, FF/VI 100/25 µg PM, and placebo in Treatment Periods 1, 2, and 3, respectively. Participants received all treatments once a day in the evening from a DPI for 14 days. Each 14 day treatment period was followed by a 14-21 day washout period.	Sequence 4: FF/VI 100/25 µg AM, Placebo, FF/VI 100/25 µg PM Participants received FF/VI 100/25 µg AM, placebo, and FF/VI 100/25 µg PM in Treatment Periods 1, 2, and 3, respectively. Participants received all treatments once a day in the evening from a DPI for 14 days. Each 14 day treatment period was followed by a 14-21 day washout period.	Sequence 5: FF/VI 100/25 µg PM, Placebo, FF/VI 100/25 µg AM Participants received FF/VI 100/25 µg PM, placebo, and FF/VI 100/25 µg AM in Treatment Periods 1, 2, and 3, respectively. Participants received all treatments once a day in the evening from a DPI for 14 days. Each 14 day treatment period was followed by a 14-21 day washout period.	Sequence 6: FF/VI 100/25 µg PM, FF/VI 100/25 µg AM, Placebo Participants received FF/VI 100/25 µg PM, FF/VI 100/25 µg AM, and placebo in Treatment Periods 1, 2, and 3, respectively. Participants received all treatments once a day in the evening from a DPI for 14 days. Each 14 day treatment period was followed by a 14-21 day washout period.
Treatment Period 1 STARTED	4	4	4	4	5	5
Treatment Period 1 COMPLETED	4	4	4	4	4	4
Treatment Period 1 NOT COMPLETED	0	0	0	0	1	1
Washout Period 1 STARTED	4	4	4	4	4	4
Washout Period 1 COMPLETED	4	4	4	4	4	4
Washout Period 1 NOT COMPLETED	0	0	0	0	0	0
Treatment Period 2 STARTED	4	4	4	4	4	4
Treatment Period 2 COMPLETED	4	4	4	4	4	4
Treatment Period 2 NOT COMPLETED	0	0	0	0	0	0
Washout Period 2 STARTED	4	4	4	4	4	4
Washout Period 2 COMPLETED	4	4	4	4	4	4
Washout Period 2 NOT COMPLETED	0	0	0	0	0	0
Treatment Period 3 STARTED	4	4	4	4	4	4
Treatment Period 3 COMPLETED	4	4	4	4	4	4
Treatment Period 3 NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 1: Placebo, FF/VI 100/25 µg AM, FF/VI 100/25 µg PM Participants received placebo, Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) AM, and FF/VI 100/25 µg PM in Treatment Periods 1, 2, and 3, respectively. Participants received all treatments once a day (OD) in the evening from a Dry Powder Inhaler (DPI) for 14 days. Each 14 day treatment period was followed by a 14-21 day washout period.	Sequence 2: Placebo, FF/VI 100/25 µg PM, FF/VI 100/25 µg AM Participants received placebo, FF/VI 100/25 µg PM, and FF/VI 100/25 µg AM in Treatment Periods 1, 2, and 3, respectively. Participants received all treatments once a day in the evening from a DPI for 14 days. Each 14 day treatment period was followed by a 14-21 day washout period.	Sequence 3: FF/VI 100/25 µg AM, FF/VI 100/25 µg PM, Placebo Participants received FF/VI 100/25 µg AM, FF/VI 100/25 µg PM, and placebo in Treatment Periods 1, 2, and 3, respectively. Participants received all treatments once a day in the evening from a DPI for 14 days. Each 14 day treatment period was followed by a 14-21 day washout period.	Sequence 4: FF/VI 100/25 µg AM, Placebo, FF/VI 100/25 µg PM Participants received FF/VI 100/25 µg AM, placebo, and FF/VI 100/25 µg PM in Treatment Periods 1, 2, and 3, respectively. Participants received all treatments once a day in the evening from a DPI for 14 days. Each 14 day treatment period was followed by a 14-21 day washout period.	Sequence 5: FF/VI 100/25 µg PM, Placebo, FF/VI 100/25 µg AM Participants received FF/VI 100/25 µg PM, placebo, and FF/VI 100/25 µg AM in Treatment Periods 1, 2, and 3, respectively. Participants received all treatments once a day in the evening from a DPI for 14 days. Each 14 day treatment period was followed by a 14-21 day washout period.	Sequence 6: FF/VI 100/25 µg PM, FF/VI 100/25 µg AM, Placebo Participants received FF/VI 100/25 µg PM, FF/VI 100/25 µg AM, and placebo in Treatment Periods 1, 2, and 3, respectively. Participants received all treatments once a day in the evening from a DPI for 14 days. Each 14 day treatment period was followed by a 14-21 day washout period.
Treatment Period 1 Adverse Event	0	0	0	0	1	0
Treatment Period 1 Withdrawal by Subject	0	0	0	0	0	1

Baseline Characteristics

A Study in Asthmatic Patients to Determine if There is Any Difference in Dosing With Fluticasone Furoate/Vilanterol Inhalation Powder in the Morning or Evening on Lung Function

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo, FF/VI 100/25 µg AM, FF/VI 100/25 µg PM in 1 of 6 Seq n=26 Participants All participants received one of the following three treatments in one of three treatment periods from the Dry Powder Inhaler (DPI) for 14 days: placebo in the morning (AM) and evening (PM), Fluticasone Furoate (FF)/Vilanterol (VI) inhalation powder 100/25 micrograms (µg) AM and placebo PM, and FF/VI inhalation powder 100/25 µg PM and placebo AM. Participants were randomized to receive treatment in one of the six following sequences (seq): (1) placebo, FF/VI 100/25 µg AM, FF/VI 100/25 µg PM; (2) placebo, FF/VI 100/25 µg PM, FF/VI 100/25 µg AM; (3) FF/VI 100/25 µg AM, FF/VI 100/25 µg PM, placebo; (4) FF/VI 100/25 µg AM, placebo, FF/VI 100/25 µg PM; (5) FF/VI 100/25 µg PM, placebo, FF/VI 100/25 µg AM; (6) FF/VI 100/25 µg PM, FF/VI 100/25 µg AM, placebo. Each 14 day treatment period was followed by a 14-21 day washout period.
Age, Continuous	38.1 Years STANDARD_DEVIATION 11.30 • n=93 Participants
Gender Female	8 Participants n=93 Participants
Gender Male	18 Participants n=93 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	25 Participants n=93 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants n=93 Participants

PRIMARY outcome

Timeframe: Pre-dose on Day 14 to 24 hours post-dose

Population: Intent-to-Treat (ITT) Population: all participants who were randomized and received at least one dose of study medication and provided at least one post-dose peak expiratory flow (PEF) or FEV1 measurement. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received placebo in the morning (AM) and evening (PM) from the Dry Powder Inhaler (DPI) for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.	FF/VI 100/25 µg AM n=24 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) inhalation powder 100/25 micrograms (µg) AM and placebo PM from the DPI for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.	FF/VI 100/25 µg PM n=25 Participants Participants received FF/VI inhalation powder 100/25 µg PM and placebo AM from the DPI for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.
Weighted Mean Forced Expiratory Volume in One Second (FEV1) Over 0-24 Hours Post-dose on Day 14	2.811 Liters Interval 2.729 to 2.893	3.188 Liters Interval 3.112 to 3.265	3.233 Liters Interval 3.159 to 3.306

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants daily in the morning and evening just prior to each dose, using an electronic peak flow meter, throughout the 14-day Treatment Period. Only the averaged daily AM and PM PEF over Days 2 to 12 was analyzed. The analysis was performed using a mixed effect analysis of covariance model with fixed effect terms for treatment and period; baseline PEF AM and PM, gender and age fitted as covariates; and participant as a random effect. Participant 122 received FF/VI 100/25 PM in treatment periods 1 and 3 and contributed twice to the summary of FF/VI 100/25 PM (n=26). Participant 123 received Placebo in treatment periods 2 and 3 and contributed twice to the summary of Placebo (n=24).

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants received placebo in the morning (AM) and evening (PM) from the Dry Powder Inhaler (DPI) for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.	FF/VI 100/25 µg AM n=24 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) inhalation powder 100/25 micrograms (µg) AM and placebo PM from the DPI for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.	FF/VI 100/25 µg PM n=26 Participants Participants received FF/VI inhalation powder 100/25 µg PM and placebo AM from the DPI for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.
Pre-treatment PEF (AM and PM) on Days 1-12. AM Mean PEF, n= 24, 24, 25	466.3 Liters per minute Interval 448.8 to 483.9	510.4 Liters per minute Interval 492.9 to 527.8	535.3 Liters per minute Interval 518.1 to 552.5
Pre-treatment PEF (AM and PM) on Days 1-12. PM Mean PEF , n= 24, 24, 26	453.2 Liters per minute Interval 438.5 to 467.9	517.6 Liters per minute Interval 503.0 to 532.2	521.4 Liters per minute Interval 507.1 to 535.7

SECONDARY outcome

Timeframe: Day 14

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured electronically by spirometry at Day 14. Trough FEV1 is defined as pre-dose (AM and PM) FEV1 measurement taken on Day 14. The analysis was performed using a mixed effects analysis of covariance model with fixed effect terms for treatment and period; and participant baseline, period baseline, gender and age fitted as covariates; and participant as a random effect. Participant 122 received FF/VI 100/25 PM in treatment periods 1 and 3 and contributed twice to the summary of FF/VI 100/25 PM (n=25). Participant 123 received Placebo in treatment periods 2 and 3 and contributed twice to the summary of Placebo (n=23).

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Participants received placebo in the morning (AM) and evening (PM) from the Dry Powder Inhaler (DPI) for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.	FF/VI 100/25 µg AM n=24 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) inhalation powder 100/25 micrograms (µg) AM and placebo PM from the DPI for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.	FF/VI 100/25 µg PM n=25 Participants Participants received FF/VI inhalation powder 100/25 µg PM and placebo AM from the DPI for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.
AM and PM Pre-treatment Trough FEV1 on Day 14 AM, n=22, 24, 25	2.788 Liters Interval 2.684 to 2.892	3.191 Liters Interval 3.087 to 3.295	3.285 Liters Interval 3.187 to 3.383
AM and PM Pre-treatment Trough FEV1 on Day 14 PM, n=23, 24, 25	2.879 Liters Interval 2.775 to 2.982	3.153 Liters Interval 3.049 to 3.258	3.188 Liters Interval 3.088 to 3.288

SECONDARY outcome

Timeframe: From the first dose of the study medication until the Follow-up Visit (up to 18 weeks)

Population: All Subjects Population: all participants who received at least one dose of the study medication.

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, associated with liver injury and impaired liver function defined as alanine aminotransferase \>=3 x upper limit of normal (ULN) and total bilirubin \>=2 x ULN or international normalised ratio \>1.5. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations. Refer to the general AE/SAE module for a list of AEs and SAEs.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Participants received placebo in the morning (AM) and evening (PM) from the Dry Powder Inhaler (DPI) for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.	FF/VI 100/25 µg AM n=24 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) inhalation powder 100/25 micrograms (µg) AM and placebo PM from the DPI for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.	FF/VI 100/25 µg PM n=25 Participants Participants received FF/VI inhalation powder 100/25 µg PM and placebo AM from the DPI for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.
Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) Any AE	8 Participants	11 Participants	12 Participants
Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) Any SAE	0 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

FF/VI 100/25 µg AM

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

FF/VI 100/25 µg PM

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=23 participants at risk Participants received placebo in the morning (AM) and evening (PM) from the Dry Powder Inhaler (DPI) for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.	FF/VI 100/25 µg AM n=24 participants at risk Participants received Fluticasone Furoate (FF)/Vilanterol (VI) inhalation powder 100/25 micrograms (µg) AM and placebo PM from the DPI for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.	FF/VI 100/25 µg PM n=25 participants at risk Participants received FF/VI inhalation powder 100/25 µg PM and placebo AM from the DPI for 14 days during one of the three treatment periods. Each 14 day treatment period was followed by a 14-21 day washout period.
Nervous system disorders Headache	26.1% 6/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	25.0% 6/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	32.0% 8/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Nervous system disorders Paraesthesia	0.00% 0/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.2% 1/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Infections and infestations Nasopharyngitis	13.0% 3/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	12.5% 3/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	8.0% 2/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Infections and infestations Gastroenteritis	0.00% 0/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	8.0% 2/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Infections and infestations Oral herpes	4.3% 1/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Infections and infestations Upper respiratory tract infection	0.00% 0/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.2% 1/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.3% 1/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.2% 1/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.0% 1/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Gastrointestinal disorders Toothache	0.00% 0/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.2% 1/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Gastrointestinal disorders Vomiting	0.00% 0/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.0% 1/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.2% 1/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.0% 1/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
General disorders Influenza like illness	0.00% 0/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.2% 1/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Immune system disorders Seasonal allergy	4.3% 1/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.2% 1/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.2% 1/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Skin and subcutaneous tissue disorders Rash	0.00% 0/23 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/24 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.0% 1/25 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 18). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.