Trial Outcomes & Findings for Bronchodilatory Efficacy of a Single Dose QMF149 (Indacaterol Maleate/Mometasone Furoate) Via the Twisthaler® Device in Adult Patients With Asthma (NCT NCT00556673)

NCT ID: NCT00556673

Last Updated: 2013-04-22

Results Overview

FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from the period baseline to 24 hour post dose trough FEV1 after 1 day of treatment was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose FEV1 as covariate.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 31 participants
• Primary outcome timeframe: Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16).
• Results posted on: 2013-04-22

Participant Flow

Participant milestones

Measure	Indacaterol/Mometasone - Placebo In Treatment Period 1 (Day 1) participants received 2 inhalations of indacaterol maleate 250 μg/mometasone furoate 200 μg once a day in the morning via the Twisthaler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of placebo via the Twisthaler device once a day in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg/salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.	Placebo - Indacaterol/Mometasone In Treatment Period 1 (Day 1) participants received 2 inhalations of placebo in the morning via the Twisthaler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of indacaterol maleate 250 μg/mometasone furoate 200 μg via the Twisthaler device in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg/salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.
Overall Study STARTED	16	15
Overall Study Pharmacodynamic (PD) Population	12	12
Overall Study COMPLETED	13	13
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Measure	Indacaterol/Mometasone - Placebo In Treatment Period 1 (Day 1) participants received 2 inhalations of indacaterol maleate 250 μg/mometasone furoate 200 μg once a day in the morning via the Twisthaler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of placebo via the Twisthaler device once a day in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg/salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.	Placebo - Indacaterol/Mometasone In Treatment Period 1 (Day 1) participants received 2 inhalations of placebo in the morning via the Twisthaler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of indacaterol maleate 250 μg/mometasone furoate 200 μg via the Twisthaler device in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg/salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.
Overall Study Protocol deviation	3	2

Baseline Characteristics

Bronchodilatory Efficacy of a Single Dose QMF149 (Indacaterol Maleate/Mometasone Furoate) Via the Twisthaler® Device in Adult Patients With Asthma

Baseline characteristics by cohort

Measure	Indacaterol/Mometasone - Placebo n=16 Participants In Treatment Period 1 (Day 1) participants received 2 inhalations of indacaterol maleate 250 μg/mometasone furoate 200 μg once a day in the morning via the Twisthaler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of placebo via the Twisthaler device once a day in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg/salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.	Placebo - Indacaterol/Mometasone n=15 Participants In Treatment Period 1 (Day 1) participants received 2 inhalations of placebo in the morning via the Twisthaler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of indacaterol maleate 250 μg/mometasone furoate 200 μg via the Twisthaler device in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg/salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.	Total n=31 Participants Total of all reporting groups
Age Continuous	39.1 years STANDARD_DEVIATION 11.93 • n=5 Participants	41.5 years STANDARD_DEVIATION 7.23 • n=7 Participants	40.3 years STANDARD_DEVIATION 9.85 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16).

Population: Pharmacodynamic population included all patients randomized that received at least one dose of study drug and completed the first two treatment periods with evaluable data for the primary efficacy variable, and with no major protocol deviations. 7 patients who were inadvertently unblinded by the investigator were excluded from the PD analysis.

FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from the period baseline to 24 hour post dose trough FEV1 after 1 day of treatment was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose FEV1 as covariate.

Outcome measures

Measure	Indacaterol/Mometasone n=24 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo n=24 Participants Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol n=24 Participants Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Change From Period Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)	0.27 liters Interval 0.19 to 0.36	-0.12 liters Interval -0.21 to -0.04	0.37 liters Interval 0.28 to 0.47

SECONDARY outcome

Timeframe: Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose.

Population: Pharmacodynamic population

FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Peak FEV1 is defined as the peak FEV1 between 0 and 4 hours post-dose. The change from baseline in peak FEV1 was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose FEV1 as covariate.

Outcome measures

Measure	Indacaterol/Mometasone n=24 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo n=24 Participants Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol n=24 Participants Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)	0.64 liters Interval 0.55 to 0.73	0.26 liters Interval 0.17 to 0.34	0.62 liters Interval 0.54 to 0.71

SECONDARY outcome

Timeframe: Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16).

Population: Pharmacodynamic population

Trough FEV1 was measured 24 hours post-dose. The FEV1 percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 % predicted indicates improvement in lung function. Change from baseline in trough FEV1 % predicted was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose value as covariate.

Outcome measures

Measure	Indacaterol/Mometasone n=24 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo n=24 Participants Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol n=24 Participants Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Change From Period Baseline in Trough Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)	6.95 Percent of predicted Interval 4.68 to 9.22	-2.87 Percent of predicted Interval -5.14 to -0.59	9.85 Percent of predicted Interval 7.58 to 12.12

SECONDARY outcome

Timeframe: Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose.

Population: Pharmacodynamic population

Peak FEV1 was defined as the peak FEV1 up to 4 hours post-dose. The FEV1 percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 % predicted indicates improvement in lung function. Change from baseline in peak FEV1 % predicted was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose value as covariate.

Outcome measures

Measure	Indacaterol/Mometasone n=24 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo n=24 Participants Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol n=24 Participants Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Change From Period Baseline in Peak Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)	16.27 Percent of predicted Interval 14.24 to 18.29	6.85 Percent of predicted Interval 4.83 to 8.88	16.49 Percent of predicted Interval 14.47 to 18.51

SECONDARY outcome

Timeframe: Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16).

Population: Pharmacodynamic population

Vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Trough FVC was measured 24 hours post-dose. Change form baseline in trough FVC was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose value as covariate.

Outcome measures

Measure	Indacaterol/Mometasone n=24 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo n=24 Participants Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol n=24 Participants Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Change From Period Baseline in Trough Forced Vital Capacity (FVC)	0.22 liters Interval 0.13 to 0.31	-0.14 liters Interval -0.23 to -0.05	0.17 liters Interval 0.08 to 0.27

SECONDARY outcome

Timeframe: Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose.

Population: Pharmacodynamic population

Vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Peak FVC was measured up to 4 hours post-dose. Change from baseline in peak FVC was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose value as covariate.

Outcome measures

Measure	Indacaterol/Mometasone n=24 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo n=24 Participants Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol n=24 Participants Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Change From Period Baseline in Peak Forced Vital Capacity (FVC)	0.47 liters Interval 0.38 to 0.55	0.20 liters Interval 0.12 to 0.29	0.35 liters Interval 0.27 to 0.44

SECONDARY outcome

Timeframe: Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16).

Population: Pharmacodynamic population

The forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio represents the proportion of a person's vital capacity that they are able to expire in the first second of an expiration. Trough FEV1/FVC was calculated from measurements taken 24 hours post-dose. Change from baseline in trough FEV1/FVC ratio was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose value as covariate.

Outcome measures

Measure	Indacaterol/Mometasone n=24 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo n=24 Participants Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol n=24 Participants Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Change From Period Baseline in Trough FEV1/FVC Ratio	2.50 ratio Interval 2.28 to 2.72	2.15 ratio Interval 1.93 to 2.37	2.65 ratio Interval 2.43 to 2.87

SECONDARY outcome

Timeframe: Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose.

Population: Pharmacodynamic population

The forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio represents the proportion of a person's vital capacity that they are able to expire in the first second of an expiration. Peak FEV1/FVC was calculated from spirometry measurements taken up to 4 hours post-dose. Change from baseline in peak FEV1/FVC ratio was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose value as covariate.

Outcome measures

Measure	Indacaterol/Mometasone n=24 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo n=24 Participants Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol n=24 Participants Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Change From Period Baseline in Peak FEV1/FVC Ratio	2.86 ratio Interval 2.63 to 3.1	2.53 ratio Interval 2.3 to 2.76	2.90 ratio Interval 2.67 to 3.14

SECONDARY outcome

Timeframe: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, and 12 hours post-dose.

Population: All participants with evaluable pharmacokinetic (PK) parameter data were included in the PK data analysis.

Outcome measures

Measure	Indacaterol/Mometasone n=29 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Area Under the Concentration-time Curve From Time 0 to 12 Hours Post-dose for Mometasone Furoate	287 pg*h/mL Standard Deviation 140	—	—

SECONDARY outcome

Timeframe: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.

Population: All participants with evaluable pharmacokinetic (PK) parameter data were included in the PK data analysis.

Outcome measures

Measure	Indacaterol/Mometasone n=29 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose for Mometasone Furoate	389 pg*h/mL Standard Deviation 191	—	—

SECONDARY outcome

Timeframe: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.

Population: All participants with evaluable pharmacokinetic (PK) parameter data were included in the PK data analysis.

Outcome measures

Measure	Indacaterol/Mometasone n=28 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose for Indacaterol	1331 pg*h/mL Standard Deviation 712	—	—

SECONDARY outcome

Timeframe: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.

Population: All participants with evaluable pharmacokinetic (PK) parameter data were included in the PK data analysis.

Outcome measures

Measure	Indacaterol/Mometasone n=29 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Maximum (Peak) Plasma Concentration (Cmax) of Mometasone Furoate	47.3 pg/mL Standard Deviation 20.9	—	—

SECONDARY outcome

Timeframe: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.

Population: All participants with evaluable pharmacokinetic (PK) parameter data were included in the PK data analysis.

Outcome measures

Measure	Indacaterol/Mometasone n=28 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Maximum (Peak) Plasma Concentration (Cmax) of Indacaterol	289 pg/mL Standard Deviation 133	—	—

SECONDARY outcome

Timeframe: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.

Population: All participants with evaluable pharmacokinetic (PK) parameter data were included in the PK data analysis.

Outcome measures

Measure	Indacaterol/Mometasone n=29 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Time to Reach Peak or Maximum Concentration Following Drug Administration for Mometasone Furoate	1.05 hours Interval 0.25 to 2.08	—	—

SECONDARY outcome

Timeframe: Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.

Population: All participants with evaluable pharmacokinetic (PK) parameter data were included in the PK data analysis.

Outcome measures

Measure	Indacaterol/Mometasone n=28 Participants Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Time to Reach Peak or Maximum Concentration Following Drug Administration for Indacaterol	0.325 hours Interval 0.267 to 0.617	—	—

Adverse Events

Indacaterol/Mometasone

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Fluticasone/Salmeterol

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Indacaterol/Mometasone n=29 participants at risk Participants received a single dose of indacaterol/mometasone 500/400 μg delivered via the TWISTHALER device (2 inhalations of 250/200 μg) in the morning.	Placebo n=28 participants at risk Participants received 2 inhalations of placebo to indacaterol/mometasone via the TWISTHALER device in the morning.	Fluticasone/Salmeterol n=26 participants at risk Participants received fluticasone/salmeterol 250/50 μg via dry powder inhaler (DPI), one inhalation in the morning and one inhalation the following evening.
Gastrointestinal disorders Dyspepsia	0.00% 0/29	3.6% 1/28	0.00% 0/26
Gastrointestinal disorders Nausea	3.4% 1/29	0.00% 0/28	0.00% 0/26
Gastrointestinal disorders Tongue coated	3.4% 1/29	3.6% 1/28	0.00% 0/26
General disorders Catheter site haematoma	3.4% 1/29	0.00% 0/28	0.00% 0/26
Infections and infestations Nasopharyngitis	0.00% 0/29	0.00% 0/28	3.8% 1/26
Infections and infestations Oral candidiasis	3.4% 1/29	0.00% 0/28	0.00% 0/26
Infections and infestations Rhinitis	0.00% 0/29	3.6% 1/28	0.00% 0/26
Infections and infestations Vulvovaginal mycotic infection	3.4% 1/29	0.00% 0/28	0.00% 0/26
Musculoskeletal and connective tissue disorders Neck pain	3.4% 1/29	0.00% 0/28	0.00% 0/26
Musculoskeletal and connective tissue disorders Torticollis	0.00% 0/29	3.6% 1/28	0.00% 0/26
Nervous system disorders Headache	13.8% 4/29	10.7% 3/28	3.8% 1/26
Psychiatric disorders Restlessness	3.4% 1/29	0.00% 0/28	0.00% 0/26
Reproductive system and breast disorders Premenstrual syndrome	3.4% 1/29	0.00% 0/28	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Cough	17.2% 5/29	3.6% 1/28	0.00% 0/26

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER