Confirmatory Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)

A 52-week Treatment, Multi-center, Randomized, Open Label, Parallel Group Study to Assess the Long Term Safety and Efficacy of Indacaterol (300 µg o.d.) Using Salmeterol (50 µg b.i.d.) as an Active Control in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00876694

Enrollment

186

Registered

2009-04-07

Start date

2009-03-31

Completion date

2010-10-31

Last updated

2011-11-08

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

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

COPD, Chronic Obstructive Pulmonary Disease, Indacaterol, long acting β2-agonist

Brief summary

This study is designed to collect long term safety data of indacaterol (300 µg o.d.) in Japanese patients with moderate to severe COPD. Data from this study will be used for the registration of indacaterol in Japan.

Interventions

DRUGIndacaterol 300 µg

Indacaterol 300 µg once daily (od) via SDDPI

DRUGSalmeterol 50 µg

Salmeterol 50 µg twice daily (bid) via Diskus®

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

40 Years to No maximum

Healthy volunteers

Inclusion criteria

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

Exclusion criteria

1. Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period 2. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1 3. Patients with concomitant pulmonary disease 4. Patients with a history of asthma 5. Patients with diabetes Type I or uncontrolled diabetes Type II 6. Any patient with lung cancer or a history of lung cancer 7. Patients with a history of certain cardiovascular comorbid conditions 8. Patients who have been exposed to indacaterol previously. (Except for any patient who enrolled in Study CQAB149B1302) Other protocol-defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
The Number of Participants With a Clinically Notable Diastolic Blood Pressure During 52 Weeks of Treatment	52 weeks	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.
The Number of Participants With a Clinically Notable Pulse Rate During 52 Weeks of Treatment	52 weeks	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.
The Number of Participants With a Clinically Notable Systolic Blood Pressure During 52 Weeks of Treatment	52 weeks	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.
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 4, 8, 12, 24, 36, 44, and 52	4, 8, 12, 24, 36, 44, and 52 weeks	The least squares mean of the blood glucose in mmol/L at weeks 4, 8, 12, 24, 36, 44 and 52. Mixed model used baseline blood glucose as a covariate.
The Number of Participants With a Clinically Notable QTc Interval Value During 52 Weeks of Treatment	52 weeks	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 baseline at any time during the study was also tabulated with absolute and relative frequencies for categories 30- 60 ms and \>60 ms.
Serum Potassium (mmol/L) at Weeks 4, 8, 12, 24, 36, 44, and 52	4, 8, 12, 24, 36, 44, and 52 weeks	The least squares mean of the serum potassium in mmol/L at weeks 4, 8, 12, 24, 36, 44 and 52. Mixed model used baseline serum potassium as a covariate.

Secondary

Measure	Time frame	Description
Trough Forced Expiratory Volume in 1 Second (FEV1) After 12, 24 and 52 Weeks	After 12, 24 and 52 weeks	Trough FEV1 was defined as the mean of the values at 23 h 10 min and 23 h 45 min after dosing at clinic on the previous day. Trough FEV1 was analyzed after 12, 24 and 52 weeks using a mixed model which contained the baseline FEV1 measurement, FEV1 prior to inhalation and FEV1 30 minutes post inhalation of salbutamol as covariates.

Countries

Japan

Participant flow

Participants by arm

Arm	Count
Indacaterol 300 μg Indacaterol 300 μg once a day (o.d.) delivered via single dose dry powder inhaler (SDDPI). Daily ICS monotherapy, if needed, was allowed to remain stable throughout study. Salbutamol was available for rescue use throughout study.	125
Salmeterol 50 μg Salmeterol 50 μg twice a day (b.i.d.) delivered via Diskus®. Daily ICS monotherapy, if needed, was allowed to remain stable throughout study. Salbutamol was available for rescue use throughout study.	61
Total	186

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Abnormal test procedure result(s)	1	0
Overall Study	Administrative problems	1	1
Overall Study	Adverse Event	10	7
Overall Study	Death	1	0
Overall Study	Subject withdrew consent	6	4
Overall Study	Unsatisfactory therapeutic effect	2	0

Baseline characteristics

Characteristic	Indacaterol 300 μg	Salmeterol 50 μg	Total
Age Continuous	70 years STANDARD_DEVIATION 7.81	67.3 years STANDARD_DEVIATION 8.05	69.1 years STANDARD_DEVIATION 7.97
Sex: Female, Male Female	9 Participants	1 Participants	10 Participants
Sex: Female, Male Male	116 Participants	60 Participants	176 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	61 / 125	26 / 61
serious Total, serious adverse events	16 / 125	4 / 61

Outcome results

Primary

Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 4, 8, 12, 24, 36, 44, and 52

The least squares mean of the blood glucose in mmol/L at weeks 4, 8, 12, 24, 36, 44 and 52. Mixed model used baseline blood glucose as a covariate.

Time frame: 4, 8, 12, 24, 36, 44, and 52 weeks