Trial Outcomes & Findings for Confirmatory Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT00876694)

NCT ID: NCT00876694

Last Updated: 2011-11-08

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: 186 participants
• Primary outcome timeframe: 52 weeks
• Results posted on: 2011-11-08

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	125	61
Overall Study COMPLETED	104	49
Overall Study NOT COMPLETED	21	12

Reasons for withdrawal

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

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Indacaterol 300 μg n=125 Participants 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.	Salmeterol 50 μg n=61 Participants 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.	Total n=186 Participants Total of all reporting groups
Age Continuous	70 years STANDARD_DEVIATION 7.81 • n=93 Participants	67.3 years STANDARD_DEVIATION 8.05 • n=4 Participants	69.1 years STANDARD_DEVIATION 7.97 • n=27 Participants
Sex: Female, Male Female	9 Participants n=93 Participants	1 Participants n=4 Participants	10 Participants n=27 Participants
Sex: Female, Male Male	116 Participants n=93 Participants	60 Participants n=4 Participants	176 Participants n=27 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: The safety population included all patients who received at least one dose of study drug.

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.

Outcome measures

Measure	Indacaterol 300 μg n=125 Participants 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.	Salmeterol 50 μg n=61 Participants 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.
The Number of Participants With a Clinically Notable Pulse Rate During 52 Weeks of Treatment Low Pulse Rate:	1 Participants	0 Participants
The Number of Participants With a Clinically Notable Pulse Rate During 52 Weeks of Treatment High Pulse Rate:	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: The safety population included all patients who received at least one dose of study drug.

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

Measure	Indacaterol 300 μg n=125 Participants 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.	Salmeterol 50 μg n=61 Participants 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.
The Number of Participants With a Clinically Notable Systolic Blood Pressure During 52 Weeks of Treatment Low Systolic Blood Pressure:	0 Participants	0 Participants
The Number of Participants With a Clinically Notable Systolic Blood Pressure During 52 Weeks of Treatment High Systolic Blood Pressure:	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: The safety population included all patients who received at least one dose of study drug.

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

Measure	Indacaterol 300 μg n=125 Participants 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.	Salmeterol 50 μg n=61 Participants 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.
The Number of Participants With a Clinically Notable Diastolic Blood Pressure During 52 Weeks of Treatment Low Diastolic Blood Pressure:	0 Participants	1 Participants
The Number of Participants With a Clinically Notable Diastolic Blood Pressure During 52 Weeks of Treatment High Diastolic Blood Pressure:	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: The safety population included all patients who received at least one dose of study drug.

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.

Outcome measures

Measure	Indacaterol 300 μg n=125 Participants 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.	Salmeterol 50 μg n=61 Participants 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.
The Number of Participants With a Clinically Notable QTc Interval Value During 52 Weeks of Treatment Notable QTc	6 Participants	3 Participants
The Number of Participants With a Clinically Notable QTc Interval Value During 52 Weeks of Treatment QTc increase from BL: 30-60 ms	12 Participants	3 Participants
The Number of Participants With a Clinically Notable QTc Interval Value During 52 Weeks of Treatment QTc increase from BL: >60 ms	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 4, 8, 12, 24, 36, 44, and 52 weeks

Population: The safety population included all patients who received at least one dose of study drug.

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.

Outcome measures

Measure	Indacaterol 300 μg n=125 Participants 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.	Salmeterol 50 μg n=61 Participants 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.
Serum Potassium (mmol/L) at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 8 (n= 121, 56)	4.30 mmol/L Standard Error 0.032	4.27 mmol/L Standard Error 0.044
Serum Potassium (mmol/L) at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 4 (n= 122, 57)	4.26 mmol/L Standard Error 0.028	4.28 mmol/L Standard Error 0.039
Serum Potassium (mmol/L) at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 12 (n= 118, 56)	4.28 mmol/L Standard Error 0.033	4.35 mmol/L Standard Error 0.044
Serum Potassium (mmol/L) at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 24 (n= 113, 52)	4.34 mmol/L Standard Error 0.035	4.27 mmol/L Standard Error 0.048
Serum Potassium (mmol/L) at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 36 (n= 106, 50)	4.35 mmol/L Standard Error 0.032	4.29 mmol/L Standard Error 0.044
Serum Potassium (mmol/L) at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 44 (n= 104, 50)	4.31 mmol/L Standard Error 0.033	4.27 mmol/L Standard Error 0.044
Serum Potassium (mmol/L) at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 52 (n= 104, 49)	4.32 mmol/L Standard Error 0.035	4.31 mmol/L Standard Error 0.048

PRIMARY outcome

Timeframe: 4, 8, 12, 24, 36, 44, and 52 weeks

Population: The safety population included all patients who received at least one dose of study drug.

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.

Outcome measures

Measure	Indacaterol 300 μg n=125 Participants 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.	Salmeterol 50 μg n=61 Participants 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.
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 52 (n= 104, 49)	5.96 mmol/L Standard Error 0.220	6.65 mmol/L Standard Error 0.296
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 4 (n= 122, 57)	6.10 mmol/L Standard Error 0.187	5.96 mmol/L Standard Error 0.260
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 8 (n= 121, 56)	5.92 mmol/L Standard Error 0.159	6.30 mmol/L Standard Error 0.220
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 12 (n= 118, 56)	5.97 mmol/L Standard Error 0.199	6.59 mmol/L Standard Error 0.262
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 24 (n= 113, 52)	6.16 mmol/L Standard Error 0.195	6.13 mmol/L Standard Error 0.271
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 36 (n= 106, 50)	5.95 mmol/L Standard Error 0.137	6.26 mmol/L Standard Error 0.189
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 4, 8, 12, 24, 36, 44, and 52 Week 44 (n= 104, 50)	6.09 mmol/L Standard Error 0.226	6.42 mmol/L Standard Error 0.309

SECONDARY outcome

Timeframe: After 12, 24 and 52 weeks

Population: The intention-to-treat (ITT) population included all randomized patients who received at least one dose of study drug.

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.

Outcome measures

Measure	Indacaterol 300 μg n=125 Participants 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.	Salmeterol 50 μg n=61 Participants 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.
Trough Forced Expiratory Volume in 1 Second (FEV1) After 12, 24 and 52 Weeks Week 12 (n= 122, 56)	1.40 Liters Standard Error 0.013	1.33 Liters Standard Error 0.019
Trough Forced Expiratory Volume in 1 Second (FEV1) After 12, 24 and 52 Weeks Week 24 (n= 112, 51)	1.40 Liters Standard Error 0.016	1.34 Liters Standard Error 0.022
Trough Forced Expiratory Volume in 1 Second (FEV1) After 12, 24 and 52 Weeks Week 52 (n= 105, 49)	1.39 Liters Standard Error 0.017	1.31 Liters Standard Error 0.023

Adverse Events

Indacaterol 300 μg

Serious events: 16 serious events

Other events: 61 other events

Deaths: 0 deaths

Salmeterol 50 μg

Serious events: 4 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Measure	Indacaterol 300 μg n=125 participants at risk 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.	Salmeterol 50 μg n=61 participants at risk 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.
Cardiac disorders Angina pectoris	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Eye disorders Retinal haemorrhage	0.00% 0/125 • 52 weeks Safety population.	1.6% 1/61 • 52 weeks Safety population.
Eye disorders Uveitis	0.00% 0/125 • 52 weeks Safety population.	1.6% 1/61 • 52 weeks Safety population.
Gastrointestinal disorders Colonic polyp	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
General disorders Sudden death	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Infections and infestations Appendicitis	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Infections and infestations Bronchitis	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Infections and infestations Herpes zoster	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Infections and infestations Pneumonia	2.4% 3/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Infections and infestations Upper respiratory tract infection	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Injury, poisoning and procedural complications Meniscus lesion	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Investigations Computerised tomogram abnormal	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Metabolism and nutrition disorders Decreased appetite	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Metabolism and nutrition disorders Dehydration	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Nervous system disorders Cerebral infarction	0.00% 0/125 • 52 weeks Safety population.	1.6% 1/61 • 52 weeks Safety population.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.4% 3/125 • 52 weeks Safety population.	1.6% 1/61 • 52 weeks Safety population.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.
Vascular disorders Arteriosclerosis obliterans	0.80% 1/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.

Other adverse events

Measure	Indacaterol 300 μg n=125 participants at risk 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.	Salmeterol 50 μg n=61 participants at risk 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.
Infections and infestations Bronchitis	4.0% 5/125 • 52 weeks Safety population.	6.6% 4/61 • 52 weeks Safety population.
Infections and infestations Nasopharyngitis	27.2% 34/125 • 52 weeks Safety population.	21.3% 13/61 • 52 weeks Safety population.
Infections and infestations Upper respiratory tract infection	6.4% 8/125 • 52 weeks Safety population.	4.9% 3/61 • 52 weeks Safety population.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	20.8% 26/125 • 52 weeks Safety population.	23.0% 14/61 • 52 weeks Safety population.
Respiratory, thoracic and mediastinal disorders Cough	11.2% 14/125 • 52 weeks Safety population.	0.00% 0/61 • 52 weeks Safety population.

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