Efficacy, Safety, Tolerability, and Pharmacokinetics of Indacaterol Maleate Via Concept1 or Simoon Devices
- Registration Number
- NCT01012739
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This study assessed the efficacy, safety, tolerability, and pharmacokinetics of two different formulations of indacaterol, one administered via the Concept1 device and one administered via the Simoon device. The study aimed to determine whether the novel formulation (Simoon) had a similar profile to that of the established formulation (Concept1).
- Detailed Description
This study was double-blind with regards to the Concept1, where placebo for the lactose-blended indacaterol was available. However, with regards to the Simoon, neither the subject nor the investigator was blinded due to lack of a placebo to the PulmoSphere formulation. Hence, the overall designation of the study was partially-blind.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Indacaterol 120μg-Indacaterol 60μg-placebo-Indacaterol 150μg Indacaterol 120 μg via the Simoon dry-powder inhaler In treatment period 1, patients received indacaterol 120 μg via the Simoon dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 60 μg via the Simoon DPI; in treatment period 3, patients received placebo to indacaterol via the Concept1 DPI; and in treatment period 4, patients received indacaterol 150 μg via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Indacaterol 150μg-placebo-Indacaterol 60μg-Indacaterol 120μg Indacaterol 150 μg via the Concept1 dry-powder inhaler In treatment period 1, patients received indacaterol 150 μg via the Concept1 dry-powder inhaler (DPI); in treatment period 2, patients received placebo to indacaterol via the Concept1 DPI; in treatment period 3, patients received indacaterol 60 μg via the Simoon DPI; and in treatment period 4, patients received indacaterol 120 μg via the Simoon DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Indacaterol 60μg-Indacaterol 150μg-Indacaterol 120μg-placebo Indacaterol 150 μg via the Concept1 dry-powder inhaler In treatment period 1, patients received indacaterol 60 μg via the Simoon dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 150 μg via the Concept1 DPI; in treatment period 3, patients received indacaterol 120 μg via the Simoon DPI; and in treatment period 4, patients received placebo to indacaterol via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Indacaterol 60μg-Indacaterol 150μg-Indacaterol 120μg-placebo Indacaterol 60 μg via the Simoon dry-powder inhaler In treatment period 1, patients received indacaterol 60 μg via the Simoon dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 150 μg via the Concept1 DPI; in treatment period 3, patients received indacaterol 120 μg via the Simoon DPI; and in treatment period 4, patients received placebo to indacaterol via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Indacaterol 120μg-Indacaterol 60μg-placebo-Indacaterol 150μg Indacaterol 150 μg via the Concept1 dry-powder inhaler In treatment period 1, patients received indacaterol 120 μg via the Simoon dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 60 μg via the Simoon DPI; in treatment period 3, patients received placebo to indacaterol via the Concept1 DPI; and in treatment period 4, patients received indacaterol 150 μg via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Indacaterol 120μg-Indacaterol 60μg-placebo-Indacaterol 150μg Indacaterol 60 μg via the Simoon dry-powder inhaler In treatment period 1, patients received indacaterol 120 μg via the Simoon dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 60 μg via the Simoon DPI; in treatment period 3, patients received placebo to indacaterol via the Concept1 DPI; and in treatment period 4, patients received indacaterol 150 μg via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Placebo-Indacaterol 120μg- Indacaterol 150μg- Indacaterol 60μg Indacaterol 60 μg via the Simoon dry-powder inhaler In treatment period 1, patients received placebo to indacaterol via the Concept1 dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 120 μg via the Simoon DPI; in treatment period 3, patients received indacaterol 150 μg via the Concept1 DPI; and in treatment period 4, patients received indacaterol 60 μg via the Simoon DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Indacaterol 60μg-Indacaterol 150μg-Indacaterol 120μg-placebo Indacaterol 120 μg via the Simoon dry-powder inhaler In treatment period 1, patients received indacaterol 60 μg via the Simoon dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 150 μg via the Concept1 DPI; in treatment period 3, patients received indacaterol 120 μg via the Simoon DPI; and in treatment period 4, patients received placebo to indacaterol via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Placebo-Indacaterol 120μg- Indacaterol 150μg- Indacaterol 60μg Indacaterol 120 μg via the Simoon dry-powder inhaler In treatment period 1, patients received placebo to indacaterol via the Concept1 dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 120 μg via the Simoon DPI; in treatment period 3, patients received indacaterol 150 μg via the Concept1 DPI; and in treatment period 4, patients received indacaterol 60 μg via the Simoon DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Indacaterol 150μg-placebo-Indacaterol 60μg-Indacaterol 120μg Placebo to indacaterol via the Concept1 dry-powder inhaler In treatment period 1, patients received indacaterol 150 μg via the Concept1 dry-powder inhaler (DPI); in treatment period 2, patients received placebo to indacaterol via the Concept1 DPI; in treatment period 3, patients received indacaterol 60 μg via the Simoon DPI; and in treatment period 4, patients received indacaterol 120 μg via the Simoon DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Indacaterol 120μg-Indacaterol 60μg-placebo-Indacaterol 150μg Placebo to indacaterol via the Concept1 dry-powder inhaler In treatment period 1, patients received indacaterol 120 μg via the Simoon dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 60 μg via the Simoon DPI; in treatment period 3, patients received placebo to indacaterol via the Concept1 DPI; and in treatment period 4, patients received indacaterol 150 μg via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Indacaterol 150μg-placebo-Indacaterol 60μg-Indacaterol 120μg Indacaterol 60 μg via the Simoon dry-powder inhaler In treatment period 1, patients received indacaterol 150 μg via the Concept1 dry-powder inhaler (DPI); in treatment period 2, patients received placebo to indacaterol via the Concept1 DPI; in treatment period 3, patients received indacaterol 60 μg via the Simoon DPI; and in treatment period 4, patients received indacaterol 120 μg via the Simoon DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Indacaterol 150μg-placebo-Indacaterol 60μg-Indacaterol 120μg Indacaterol 120 μg via the Simoon dry-powder inhaler In treatment period 1, patients received indacaterol 150 μg via the Concept1 dry-powder inhaler (DPI); in treatment period 2, patients received placebo to indacaterol via the Concept1 DPI; in treatment period 3, patients received indacaterol 60 μg via the Simoon DPI; and in treatment period 4, patients received indacaterol 120 μg via the Simoon DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Placebo-Indacaterol 120μg- Indacaterol 150μg- Indacaterol 60μg Indacaterol 150 μg via the Concept1 dry-powder inhaler In treatment period 1, patients received placebo to indacaterol via the Concept1 dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 120 μg via the Simoon DPI; in treatment period 3, patients received indacaterol 150 μg via the Concept1 DPI; and in treatment period 4, patients received indacaterol 60 μg via the Simoon DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Indacaterol 60μg-Indacaterol 150μg-Indacaterol 120μg-placebo Placebo to indacaterol via the Concept1 dry-powder inhaler In treatment period 1, patients received indacaterol 60 μg via the Simoon dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 150 μg via the Concept1 DPI; in treatment period 3, patients received indacaterol 120 μg via the Simoon DPI; and in treatment period 4, patients received placebo to indacaterol via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. Placebo-Indacaterol 120μg- Indacaterol 150μg- Indacaterol 60μg Placebo to indacaterol via the Concept1 dry-powder inhaler In treatment period 1, patients received placebo to indacaterol via the Concept1 dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 120 μg via the Simoon DPI; in treatment period 3, patients received indacaterol 150 μg via the Concept1 DPI; and in treatment period 4, patients received indacaterol 60 μg via the Simoon DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study.
- Primary Outcome Measures
Name Time Method Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose for Each Treatment Baseline and Day 1 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 for each treatment.
- Secondary Outcome Measures
Name Time Method Time to Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment From 5 minutes to 12 hours post-dose FEV1 was measured with spirometry conducted according to internationally accepted standards at 5, 15, and 30 minutes; 1 hour, 1 hour 30 minutes; and 1, 2, 4, 6, 8, and 12 hours post-dose in Day 1.
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose for Each Treatment From 5 minutes to 4 hours post-dose for each treatment FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time.
Indacaterol Exposure (AUC[0-24 Hours]) for Each Treatment 0 to 24 hours post-dose All patients fasted for at least 10 hours prior to administration of study medication and continued to fast for at least 4 hours thereafter. Venous blood samples for pharmacokinetic evaluation were collected at 5, 10, 15, and 30 minutes; and 1, 2, 4, 8, and 24 hours post-dose in each treatment period and were analyzed using a LC-MS/MS assay. Area under the concentration-time curve up to 24 hours (AUC\[0-24 hours\]) was calculated from concentration-time data using non-compartmental analysis.
Indacaterol Exposure (Cmax) for Each Treatment 0 to 24 hours post-dose All patients fasted for at least 10 hours prior to administration of study medication and continued to fast for at least 4 hours thereafter. Venous blood samples for pharmacokinetic evaluation were collected at 5, 10, 15, and 30 minutes; and 1, 2, 4, 8, and 24 hours post-dose in each treatment period and were analyzed using a LC-MS/MS assay. Maximum (peak) plasma drug concentration after drug administration (Cmax) was calculated from concentration-time data using non-compartmental analysis.
Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment Baseline and Day 1 FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 4, 6, 8, and 12 hours post-dose in Day 1.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇬🇧Manchester, United Kingdom