A Crossover Study to Determine the 24 Hour Lung Function Profile of Indacaterol in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)

A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, 3-period, 14-day Crossover Study to Determine the 24 Hour Lung Function Profile of Indacaterol (300 µg Once Daily [od]) in Patients With Moderate-to-severe COPD, Using Open-label Salmeterol (50 µg Twice Daily [Bis in Die, Bid]) as Active Control

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00622635

Enrollment

Registered

2008-02-25

Start date

2008-01-31

Completion date

2008-07-31

Last updated

2011-08-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

chronic obstructive pulmonary disease, COPD, indacaterol

Brief summary

This study was conducted to provide detailed information on the efficacy of indacaterol in terms of its effect on spirometry assessed forced expiratory volume in 1 second (FEV1) over a 24 hour time period.

Interventions

DRUGIndacaterol 300 μg

Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).

DRUGPlacebo to indacaterol

Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).

DRUGSalmeterol 50 μg

Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

40 Years to No maximum

Healthy volunteers

Inclusion criteria

* Diagnosis of chronic obstructive pulmonary disease (COPD) (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2006) and: 1. Smoking history of at least 20 pack-years 2. Post-bronchodilator forced expiratory volume in 1 second (FEV1) \< 80% and ≥ 30% of the predicted normal value 3. Post-bronchodilator FEV1/FVC (forced vital capacity) \< 70%

Exclusion criteria

* Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to screening or during the run-in period * Patients requiring long-term oxygen therapy (\> 15 hours a day) for chronic hypoxemia * Patients who have had a respiratory tract infection within 6 weeks prior to screening * Patients with concomitant pulmonary disease * Patients with a history of asthma * Patients with diabetes Type I or uncontrolled diabetes Type II * Any patient with lung cancer or a history of lung cancer * Any patient with active cancer or a history of cancer with less than 5 years disease-free survival time * Patients with a history of long QT syndrome or whose QTc interval (Bazett's) measured at screening or randomization is prolonged * Patients who have been vaccinated with live attenuated vaccines within 30 days prior to screening or during the run-in period * Patients unable to successfully use a dry powder inhaler device or perform spirometry measurements Other protocol-defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Each Treatment Period (Day 15)	After 14 days	FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of each treatment period. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.

Secondary

Measure	Time frame	Description
Forced Expiratory Volume in 1 Second (FEV1) 15 Minutes Post-dose at the End of Each Treatment Period (Day 14)	15 minutes post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 30 Minutes Post-dose at the End of Each Treatment Period (Day 14)	30 minutes post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 1 Hour Post-dose at the End of Each Treatment Period (Day 14)	1 hour post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 2 Hours Post-dose at the End of Each Treatment Period (Day 14)	2 hours post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 3 Hours Post-dose at the End of Each Treatment Period (Day 14)	3 hours post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 4 Hours Post-dose at the End of Each Treatment Period (Day 14)	4 hours post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 5 Hours Post-dose at the End of Each Treatment Period (Day 14)	5 hours post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 6 Hours Post-dose at the End of Each Treatment Period (Day 14)	6 hours post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 8 Hours Post-dose at the End of Each Treatment Period (Day 14)	8 hours post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 5 Minutes Post-dose at the End of Each Treatment Period (Day 14)	5 minutes post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 11 Hours 10 Minutes Post-dose at the End of Each Treatment Period (Day 14)	11 hours 10 minutes post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 11 Hours 45 Minutes Post-dose at the End of Each Treatment Period (Day 14)	11 hours 45 minutes post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 14 Hours Post-dose at the End of Each Treatment Period (Day 14)	14 hours post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 20 Hours 10 Minutes Post-dose at the End of Each Treatment Period (Day 15)	20 hours 10 minutes post-dose at the end of each treatment period (Day 15)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 20 Hours 45 Minutes Post-dose at the End of Each Treatment Period (Day 15)	20 hours 45 minutes post-dose at the end of each treatment period (Day 15)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 22 Hours Post-dose at the End of Each Treatment Period (Day 15)	22 hours post-dose at the end of each treatment period (Day 15)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 23 Hours 10 Minutes Post-dose at the End of Each Treatment Period (Day 15)	23 hours 10 minutes post-dose at the end of each treatment period (Day 15)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 23 Hours 45 Minutes Post-dose at the End of Each Treatment Period (Day 15)	23 hours 45 minutes post-dose at the end of each treatment period (Day 15)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
Forced Expiratory Volume in 1 Second (FEV1) 10 Hours Post-dose at the End of Each Treatment Period (Day 14)	10 hours post-dose at the end of each treatment period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.

Countries

Belgium, Spain, United States

Participant flow

Participants by arm

Arm	Count
Entire Study Population The entire study population included all 6 treatment groups who received indacaterol 300 µg once daily, placebo to indacaterol once daily, and salmeterol 50 µg twice daily via a single-dose (indacaterol and placebo to indacaterol) or multi-dose (salmeterol) dry-powder inhaler in 6 different sequences. Patients received each treatment for 14 days with a 14 day washout between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	68
Total	68

Arm

Count

Entire Study Population

The entire study population included all 6 treatment groups who received indacaterol 300 µg once daily, placebo to indacaterol once daily, and salmeterol 50 µg twice daily via a single-dose (indacaterol and placebo to indacaterol) or multi-dose (salmeterol) dry-powder inhaler in 6 different sequences. Patients received each treatment for 14 days with a 14 day washout between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Total

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Treatment Period 1	Abnormal test procedure result(s)	0	0	0	0	1
Treatment Period 1	Adverse Event	0	0	1	0	0
Treatment Period 1	Withdrawal by Subject	0	1	0	0	0
Treatment Period 2	Adverse Event	1	0	0	0	0
Treatment Period 3	Adverse Event	0	0	0	2	0
Treatment Period 3	Withdrawal by Subject	0	0	0	1	0

Baseline characteristics

Characteristic	Entire Study Population
Age Continuous	65.6 years STANDARD_DEVIATION 9.03
Sex: Female, Male Female	16 Participants
Sex: Female, Male Male	52 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	0 / 66	0 / 65	4 / 66
serious Total, serious adverse events	1 / 66	0 / 65	0 / 66

Outcome results

Primary

Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Each Treatment Period (Day 15)

FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of each treatment period. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.

Time frame: After 14 days