Trial Outcomes & Findings for Safety, Tolerability and Efficacy of Indacaterol in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT00677807)

Last Updated: 2011-08-22

Results Overview

The number of participants with newly occurring or worsening clinically notable vital sign: Pulse Rate in beats per minute (bpm) at anytime post baseline (BL) by treatment. Low Pulse Rate was defined as a pulse rate: \<40 bpm or \<= to 50 bpm and a decrease from baseline \>= to 15 bpm. High Pulse Rate was defined as a pulse rate: \>130 bpm or \>= to 120 bpm and an increase from baseline \>= to 15 bpm.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

415 participants

Primary outcome timeframe

Up to 52 weeks

Results posted on

2011-08-22

Participant Flow

This is an extension study to core study stage 2: CQAB149B2335S (NCT00463567).

Participant milestones

Participant milestones
Measure	Indacaterol 150 µg Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Indacaterol 300 µg Indacaterol 300 µg once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Overall Study STARTED	144	146	125
Overall Study Safety/ITT: Received Study Drug	144	146	124
Overall Study COMPLETED	126	135	105
Overall Study NOT COMPLETED	18	11	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Indacaterol 150 µg Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Indacaterol 300 µg Indacaterol 300 µg once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Overall Study Adverse Event	4	1	6
Overall Study Lack of Efficacy	0	0	2
Overall Study Participant no longer needs study drug	0	0	1
Overall Study Withdrawal by Subject	10	3	6
Overall Study Lost to Follow-up	2	2	2
Overall Study Administrative problems	1	1	2
Overall Study Death	0	1	1
Overall Study Protocol Deviation	1	3	0

Baseline Characteristics

Safety, Tolerability and Efficacy of Indacaterol in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Indacaterol 150 µg n=144 Participants Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Indacaterol 300 µg n=146 Participants Indacaterol 300 µg once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=124 Participants Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Total n=414 Participants Total of all reporting groups
Age Continuous	62.5 years STANDARD_DEVIATION 9.52 • n=5 Participants	62.5 years STANDARD_DEVIATION 9.00 • n=7 Participants	62.8 years STANDARD_DEVIATION 9.18 • n=5 Participants	62.6 years STANDARD_DEVIATION 9.21 • n=4 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	60 Participants n=7 Participants	43 Participants n=5 Participants	160 Participants n=4 Participants
Sex: Female, Male Male	87 Participants n=5 Participants	86 Participants n=7 Participants	81 Participants n=5 Participants	254 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 52 weeks

Population: Extension safety population consisting of all participants who received at least one dose of study drug in the extension study.

Outcome measures

Outcome measures
Measure	Indacaterol 150 µg n=144 Participants Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Indacaterol 300 µg n=146 Participants Indacaterol 300 µg once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=124 Participants Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
The Number of Participants With a Clinically Notable Pulse Rate During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo Low Pulse Rate	3 Participants	3 Participants	2 Participants
The Number of Participants With a Clinically Notable Pulse Rate During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo High Pulse Rate	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 52 weeks

Population: Extension safety population consisting of all participants who received at least one dose of study drug in the extension study.

The number of participants with newly occurring or worsening clinically notable vital sign: Systolic Blood Pressure (mmHg) at anytime post baseline (BL) by treatment. A Low Systolic Blood Pressure was defined as a systolic blood pressure measurement: \<75 mmHg or \<= to 90 mmHg and a decrease from baseline \>= to 20 mmHg. A High Systolic Blood Pressure was defined as a systolic blood pressure measurement: \>200 mmHg or \>= to 180 mmHg and an increase from baseline \>= to 20 mmHg.

Outcome measures

Outcome measures
Measure	Indacaterol 150 µg n=144 Participants Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Indacaterol 300 µg n=146 Participants Indacaterol 300 µg once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=124 Participants Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
The Number of Participants With a Clinically Notable Systolic Blood Pressure During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo High Systolic Blood Pressure	1 participants	2 participants	2 participants
The Number of Participants With a Clinically Notable Systolic Blood Pressure During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo Low Systolic Blood Pressure	2 participants	2 participants	2 participants

PRIMARY outcome

Timeframe: Up to 52 weeks

Population: Extension safety population consisting of all participants who received at least one dose of study drug in the extension study.

The number of participants with newly occurring or worsening clinically notable vital sign: Diastolic Blood Pressure (mmHg) at anytime post baseline (BL) by treatment. A Low Diastolic Blood Pressure was defined as a diastolic blood pressure measurement: \<40 mmHg or \<= to 50 mmHg and a decrease from baseline \>= to 15 mmHg. A High Diastolic Blood Pressure was defined as a diastolic blood pressure measurement: \>115 mmHg or \>= to 105 mmHg and an increase from baseline \>= to 15 mmHg.

Outcome measures

Outcome measures
Measure	Indacaterol 150 µg n=144 Participants Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Indacaterol 300 µg n=146 Participants Indacaterol 300 µg once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=124 Participants Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
The Number of Participants With a Clinically Notable Diastolic Blood Pressure During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo Low Diastolic Blood Pressure	6 participants	3 participants	2 participants
The Number of Participants With a Clinically Notable Diastolic Blood Pressure During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo High Diastolic Blood Pressure	1 participants	0 participants	2 participants

PRIMARY outcome

Timeframe: Up to 52 weeks

Population: Extension safety population consisting of all participants who received at least one dose of study drug in the extension study.

The number of participants with newly occurring or worsening clinically notable QTc Interval value at anytime post baseline. The QTc interval is calculated using Fridericia's formula: QTc= QT/cube root RR. QTc is the interval between the Q and T waves corrected for heart rate and RR is the interval between two R waves in milliseconds (ms). Notable QTC interval= \>450 ms for males and \>470 ms for females. The maximum QTC increase from pre to post dose at any time during the study was also tabulated with absolute and relative frequencies for categories 30- 60 ms and \>60 ms.

Outcome measures

Outcome measures
Measure	Indacaterol 150 µg n=144 Participants Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Indacaterol 300 µg n=146 Participants Indacaterol 300 µg once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=124 Participants Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
The Number of Participants With a Clinically Notable QTc Interval Value During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo Notable QTc	10 participant	9 participant	11 participant
The Number of Participants With a Clinically Notable QTc Interval Value During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo QTc increase from BL: 30-60 ms	28 participant	30 participant	30 participant
The Number of Participants With a Clinically Notable QTc Interval Value During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo QTc increase from BL: >60 ms	1 participant	1 participant	1 participant

PRIMARY outcome

Timeframe: Weeks 12, 26, 36, 44 and 52

Population: Extension safety population consisting of all participants who received at least one dose of study drug in the extension study. "n" in the categories is the number of participants with data at the given time point for each treatment.

The least squares mean of the serum potassium in mmol/L at weeks 12, 26, 36, 44 and 52. Mixed model used baseline serum potassium as a covariate.

Outcome measures

Outcome measures
Measure	Indacaterol 150 µg n=144 Participants Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Indacaterol 300 µg n=146 Participants Indacaterol 300 µg once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=124 Participants Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Serum Potassium (mmol/L) 1 Hour Post-dose at Weeks 12, 26, 36, 44 and 52 Week 12 (n=140, 138, 115)	4.45 mmol/L Standard Error 0.045	4.50 mmol/L Standard Error 0.044	4.45 mmol/L Standard Error 0.050
Serum Potassium (mmol/L) 1 Hour Post-dose at Weeks 12, 26, 36, 44 and 52 Week 26 (n=135, 141, 114)	4.53 mmol/L Standard Error 0.049	4.53 mmol/L Standard Error 0.047	4.55 mmol/L Standard Error 0.053
Serum Potassium (mmol/L) 1 Hour Post-dose at Weeks 12, 26, 36, 44 and 52 Week 36 (n=132, 133, 109)	4.46 mmol/L Standard Error 0.051	4.49 mmol/L Standard Error 0.050	4.55 mmol/L Standard Error 0.057
Serum Potassium (mmol/L) 1 Hour Post-dose at Weeks 12, 26, 36, 44 and 52 Week 44 (n=129, 130, 103)	4.52 mmol/L Standard Error 0.050	4.51 mmol/L Standard Error 0.048	4.55 mmol/L Standard Error 0.055
Serum Potassium (mmol/L) 1 Hour Post-dose at Weeks 12, 26, 36, 44 and 52 Week 52 (n=121, 129, 97)	4.42 mmol/L Standard Error 0.053	4.54 mmol/L Standard Error 0.050	4.49 mmol/L Standard Error 0.059

PRIMARY outcome

Timeframe: Weeks 12, 26, 36, 44 and 52

The least squares mean of the blood glucose in mmol/L at weeks 12, 26, 36, 44 and 52. Mixed model used baseline blood glucose as a covariate.

Outcome measures

Outcome measures
Measure	Indacaterol 150 µg n=144 Participants Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Indacaterol 300 µg n=146 Participants Indacaterol 300 µg once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=124 Participants Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 12, 26, 36, 44 and 52 Week 12 (n=142, 140, 118)	5.50 mmol/L Standard Error 0.139	5.59 mmol/L Standard Error 0.134	5.18 mmol/L Standard Error 0.150
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 12, 26, 36, 44 and 52 Week 26 (n=137, 143, 118)	5.93 mmol/L Standard Error 0.169	5.77 mmol/L Standard Error 0.160	5.49 mmol/L Standard Error 0.180
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 12, 26, 36, 44 and 52 Week 36 (n=134, 136, 111)	5.81 mmol/L Standard Error 0.156	5.75 mmol/L Standard Error 0.151	5.66 mmol/L Standard Error 0.171
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 12, 26, 36, 44 and 52 Week 44 (n=131, 133, 105)	5.70 mmol/L Standard Error 0.189	5.88 mmol/L Standard Error 0.176	5.60 mmol/L Standard Error 0.205
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 12, 26, 36, 44 and 52 Week 52 (n=123, 131, 99)	5.93 mmol/L Standard Error 0.201	5.70 mmol/L Standard Error 0.189	5.55 mmol/L Standard Error 0.221

SECONDARY outcome

Timeframe: Week 52

Population: Participants from the Extension Intent-to-treat population (consisting of all participants who received at least one dose of study drug) for whom data was available for this Outcome Measure. Missing data was imputed Last Observation Carried Forward.

Spirometry was conducted according to internationally accepted standards. The trough FEV1 was defined as the average of the FEV1 measurements taken at 23 hours 10 minutes and 23 hours 45 minutes post dose at week 52. The mixed model used baseline FEV1 as well as FEV1 reversibility components as covariates.

Outcome measures

Outcome measures
Measure	Indacaterol 150 µg n=125 Participants Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Indacaterol 300 µg n=133 Participants Indacaterol 300 µg once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=104 Participants Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 52 of Treatment	1.44 Liters Standard Error 0.034	1.45 Liters Standard Error 0.032	1.27 Liters Standard Error 0.037

SECONDARY outcome

Timeframe: Weeks 36, 44 and 52

Population: Extension Intent-to-treat population consisting of all participants who received at least one dose of study drug. "n" in each of the categories is the number of participants with data at the given time point. Missing data were imputed using LOCF but not by more than 14 weeks and not by carrying forward scores within 4 weeks of treatment start.

The least squares mean of the SGRQ total score at weeks 36, 44 and 52. Mixed model used for analysis used baseline SGRQ total score as well as FEV1 reversibility components as covariates. SGRQ is a health related quality of life questionnaire consisting of 50 items in three domains: symptoms, activity and impacts. The total score is 0 to 100 with a higher score indicating poorer health. A difference from placebo of -4 in the least squares mean SGRQ total score is considered clinically relevant.

Outcome measures

Outcome measures
Measure	Indacaterol 150 µg n=144 Participants Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Indacaterol 300 µg n=146 Participants Indacaterol 300 µg once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=124 Participants Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Quality of Life Assessment With St George's Respiratory Questionnaire (SGRQ) Total Score at Weeks 36, 44 and 52 Week 36 (n=138, 137, 113)	36.62 Score on a Scale Standard Error 1.767	36.37 Score on a Scale Standard Error 1.695	39.56 Score on a Scale Standard Error 1.913
Quality of Life Assessment With St George's Respiratory Questionnaire (SGRQ) Total Score at Weeks 36, 44 and 52 Week 44 (n= 128, 133, 109)	35.98 Score on a Scale Standard Error 1.883	36.18 Score on a Scale Standard Error 1.739	41.67 Score on a Scale Standard Error 2.001
Quality of Life Assessment With St George's Respiratory Questionnaire (SGRQ) Total Score at Weeks 36, 44 and 52 Week 52 (n=126, 132, 104)	35.97 Score on a Scale Standard Error 1.826	37.49 Score on a Scale Standard Error 1.721	39.19 Score on a Scale Standard Error 2.004

Adverse Events

Indacaterol 150 µg

Serious events: 15 serious events

Other events: 86 other events

Deaths: 0 deaths

Indacaterol 300 µg

Serious events: 18 serious events

Other events: 91 other events

Deaths: 0 deaths

Placebo

Serious events: 13 serious events

Other events: 67 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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

Measure	Indacaterol 150 µg n=144 participants at risk Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Indacaterol 300 µg n=146 participants at risk Indacaterol 300 µg once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=124 participants at risk Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Gastrointestinal disorders Diarrhoea	3.5% 5/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	3.4% 5/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	5.6% 7/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Gastrointestinal disorders Nausea	2.8% 4/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	4.1% 6/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	5.6% 7/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Infections and infestations Bronchitis	3.5% 5/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	6.2% 9/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	7.3% 9/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Infections and infestations Influenza	5.6% 8/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	3.4% 5/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	2.4% 3/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Infections and infestations Lower respiratory tract infection	3.5% 5/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	7.5% 11/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	6.5% 8/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Infections and infestations Nasopharyngitis	16.7% 24/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	17.8% 26/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	15.3% 19/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Infections and infestations Sinusitis	6.2% 9/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	7.5% 11/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	2.4% 3/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Infections and infestations Upper respiratory tract infection	11.8% 17/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	13.7% 20/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	8.1% 10/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Infections and infestations Urinary tract infection	3.5% 5/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	5.5% 8/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	3.2% 4/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Musculoskeletal and connective tissue disorders Arthralgia	3.5% 5/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	5.5% 8/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	0.81% 1/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Musculoskeletal and connective tissue disorders Back pain	2.8% 4/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	2.7% 4/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	5.6% 7/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Musculoskeletal and connective tissue disorders Muscle spasms	8.3% 12/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	2.7% 4/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	1.6% 2/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.5% 5/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	5.5% 8/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	0.81% 1/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Nervous system disorders Headache	10.4% 15/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	4.8% 7/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	4.0% 5/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	23.6% 34/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	24.7% 36/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	26.6% 33/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Respiratory, thoracic and mediastinal disorders Cough	11.8% 17/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	10.3% 15/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	6.5% 8/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.2% 9/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	2.7% 4/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	4.8% 6/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.9% 10/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	6.8% 10/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	1.6% 2/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.
Vascular disorders Hypertension	4.2% 6/144 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	2.1% 3/146 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.	5.6% 7/124 • 26 weeks Safety population consisting of all participants who received at least one dose of study drug in the extension study.