A Study to Evaluate the Effects of Indacaterol Maleate as a New Formulation in the Concept 1 Device

A Multi-centre, Randomized, Double-blind, Double-dummy, Multiple-dose, Crossover Study to Evaluate the Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of Orally Inhaled Indacaterol Administered as Either PulmoSphere or Lactose-blend Powder Via the Concept1 Device in Adult Patients With Persistent Asthma

This study will assess the pharmacodynamics, safety, tolerability and pharmacokinetics of two different formulations of indacaterol maleate, both administered via the Concept1 device. The study aims to determine whether the novel formulation has a similar clinical profile as the established formulation.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: 75 µg indacaterol maleate (LB); Drug: placebo to indacaterol (PoS); Drug: 75 µg indacaterol maleate (PoS); Drug: placebo to indacaterol (LB); Drug: 37.5 µg indacaterol maleate (PoS)

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Wiesbaden, Germany, 65187
    • Novartis Investigative Site
• United Kingdom
  • Machester, United Kingdom, M23 9QZ
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients with asthma
• Aged 18 or above
• Patients using inhaled corticosteroid (with or without long acting beta agonist)
• Patients who demonstrate an increase in FEV1 after inhaling a short acting beta agonist

Exclusion Criteria:

• Asthma exacerbations in previous 6 months
• COPD or other pulmonary disease
• Excessive use of short acting beta agonists

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 75 µg Indacaterol (LB) + Placebo (PoS); 75 µg indacaterol maleate lactose blend (LB) + placebo to indacterol PulmoSphereTM (PoS) delivered via the Concept1 device once daily in the morning for 7 days.	Drug: 75 µg indacaterol maleate (LB); 75 µg indacaterol maleate lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days.; Drug: placebo to indacaterol (PoS); Placebo to indacaterol PulmoSphereTM (PoS) delivered via the Concept1 device once daily in the morning for 7 days.
Experimental: 75 µg Indacaterol (PoS) + Placebo (LB); 75 µg indacaterol maleate PulmoSphereTM (PoS) + placebo to indacterol lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days.	Drug: 75 µg indacaterol maleate (PoS); 75 µg indacaterol maleate PulmoSphereTM (PoS) delivered via the Concept1 device once daily in the morning for 7 days.; Drug: placebo to indacaterol (LB); Placebo to indacaterol lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days.
Experimental: 37.5 µg Indacaterol (PoS) + Placebo (LB); 37.5 µg indacaterol maleate PulmoSphereTM (PoS) + placebo to indacaterol lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days.	Drug: placebo to indacaterol (LB); Placebo to indacaterol lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days.; Drug: 37.5 µg indacaterol maleate (PoS); 37.5 µg indacaterol maleate PulmoSphereTM (PoS) delivered via the Concept1 device once daily in the morning for 7 days.
Experimental: Placebo (LB) and Placebo (PoS); Placebo to indacaterol PulmoSphereTM (PoS) + placebo to indacaterol lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days.	Drug: placebo to indacaterol (PoS); Placebo to indacaterol PulmoSphereTM (PoS) delivered via the Concept1 device once daily in the morning for 7 days.; Drug: placebo to indacaterol (LB); Placebo to indacaterol lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Forced Expiratory Volume in One Second (FEV1) After 7 Days of Treatment	Spirometry was performed according to internationally accepted standards at Day 8. Trough FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Trough FEV1 was defined as the average of the FEV1 measurements at 23 hours 10 minutes and 23 hours 45 minutes post dose.at Day 8. Analysis of Covariance with treatment, period, sequence and subject nested within sequence as fixed effects and period FEV1 baseline as a covariate.	Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Forced Expiratory Volume in One Second (FEV1) After 1 Day of Treatment	Spirometry was performed according to internationally accepted standards at Day 2. Trough FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Trough FEV1 was defined as the average of the FEV1 measurements at 23 hours 10 minutes and 23 hours 45 minutes post dose at Day 2. Analysis of Covariance with treatment, period, sequence and subject nested within sequence as fixed effects and period FEV1 baseline as a covariate.	Day 2
Peak FEV1 at Day 1 and Day 7	Spirometry was performed according to internationally accepted standards at 0, 15 and 30 minutes; 1,2,3,4,8,12 hours on Day 1 and 23.16 and 23.75 hours on Day 2 after 1 day of treatment and on Day 7 and Day 8 following 7 days of treatment. Peak FEV1 was the maximum FEV1 post treatment. Analysis of Covariance with treatment, period, sequence and subject nested within sequence as fixed effects and period FEV1 baseline included as a covariate.	Day 1, Day 7
Time to Peak FEV1 at Day 1 and Day 7	Spirometry was performed according to internationally accepted standards. Time to the peak (maximum) FEV1 is recorded. Analysis of Covariance with treatment, period, sequence and subject nested within sequence as fixed effects and period FEV1 baseline as a covariate.	Day 1, Day 7
FEV1 at Each Time-Point on Day 1 and Day 2	Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8, 12 hours on Day 1 and 23.16 and 23.75 hours on Day 2. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.	Day 1, Day 2
FEV1 at Each Time-Point on Day 7 and Day 8	Spirometry was conducted according to internationally accepted standards at 0, 15 and 30 minutes; 1,2,3,4,8,12 hours on Day 7 and 23.16 and 23.75 hours on Day 8. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.	Day 7, Day 8
Forced Vital Capacity (FVC) at Each Time-Point on Day 1 and Day 2	Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8 and 12 hours on Day 1 and 23.16 and 23.75 hours on Day 2. FVC is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible.	Day 1, Day 2
Forced Vital Capacity (FVC) at Each Time-Point on Day 7 and Day 8	Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8 and 12 hours on Day 7 and 23.16 and 23.75 hours on Day 8. FVC is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible.	Day 7, Day 8
FEV1/FVC at Each Post-Dose Time Point on Day 1 and Day 2	Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8 and 12 hours on Day 1 and 23.16 and 23.75 hours on Day 2. FEV1/FVC ratio is the percentage of the total FVC that is expelled from the lungs during the first second of forced exhalation.	Day1, Day 2
FEV1/FVC at Each Post-dose Time Point on Day 7 and Day 8	Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8 and 12 hours on Day 1 and 23.16 and 23.75 hours on Day 2 after treatment. FEV1/FVC ratio is the percentage of the total FVC that is expelled from the lungs during the first second of forced exhalation.	Day 7, Day 8
Forced Expiratory Flow 25- 75% (FEF25-75) on Day 1 and Day 2	Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8 and 12 hours on Day 1 and 23.16 and 23.75 hours on Day 2. The forced expiratory flow (FEF) 25%-75% measurement describes the amount of air expelled from the lungs during the middle half (25% - 75%) of the forced vital capacity test and is measured using spirometry.	Day 1, Day 2
Forced Expiratory Flow 25- 75% (FEF25-75) on Day 7 and Day 8	Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8 and 12 hours on Day 7 and 23.16 and 23.75 hours on Day 8. The forced expiratory flow (FEF) 25%-75% measurement describes the amount of air expelled from the lungs during the middle half (25% - 75%) of the forced vital capacity test and is measured using spirometry.	Day 7, Day 8
Standardized FEV1 AUC Between Baseline (Pre-dose) and 4 Hour Post-dose (AUC0-4h)	Spirometry was conducted according to internationally accepted standards at predose, 5, 15 and 30 minutes, 1, 2 and 4 hours post-dose on Day 1 and Day 7. The standardized (with respect to the length of time) area under the curve (AUC) for FEV1 was calculated using trapezoidal rule between 5 min and 4 h post. Analysis of Covariance with treatment, period, sequence and subject nested within sequence as fixed effects and period FEV1 baseline as a covariate.	Day 1, Day 7
Standardized FEV1 AUC Between Baseline (Pre-dose) and 12 Hour Post-dose (AUC0-12h)	Spirometry was conducted according to internationally accepted standards at predose, 5 , 15 and 30 min, 1, 2, 4, 8 and 12 hours post-dose on Day 1 and Day 7. The standardized (with respect to the length of time) area under the curve (AUC) for FEV1 was calculated using trapezoidal rule between 5 min and 12 h post. Analysis of covariance with treatment, period, sequence and subject nested within sequence as fixed effects and FEV1 period baseline as a covariate.	Day 1, Day 7
Peak Expiratory Flow Rate in the Morning in the Evening	PEFR was measured on all days from Screening Visit 2 to end of study visit: twice daily pre-dose (prior to Inhaled Corticosteroids) and approximately 12 hours post-dose (during the treatment period). Each subject was provided with a PEFR meter and recorded the PEFR readings in a daily diary. repeated measures. Analysis of covariance with treatment, period, sequence, day and treatment-day interaction as fixed effect and subject as a random effect and baseline PEFR as a covariate in the model.	Up to 101 days
Number of Puffs of Rescue Medicine	Salbutamol (100 µg/puff) was used as rescued medicine. The total number of puffs per day was calculated and divided by the number of days with data to determine the mean daily number of puffs of rescue medication for each patient and was recorded in the patient diary from Baseline until Day 8 of Treatment Period 4. Analysis of covariance with treatment, period, sequence, and subject nested within sequence as fixed effect.	Up to 101 days
Number of Participants With Adverse Events as a Measure of Safety	Adverse event are defined as any unfavorable and unintended diagnosis, symptoms, sign (including an abnormal lab finding), syndrome or disease which either occurs during the study, having been absent at baseline, or if present at baseline appear to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization , cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards. Additional information about adverse events can be found in the Adverse Event section	Up to 101 days
Time to Reach Maximum Concentration (Tmax) After Drug Administration		Day1, Day 7
Observed Maximum Concentration (Cmax) After Drug Administration		Day 1, Day 7
Area Under the Curve Pre-dose to 24 Hour Post Dose (AUC0-24h)		Day 1, Day 7

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: November 15, 2011
• First Submitted That Met QC Criteria: December 1, 2011
• First Posted (Estimate): December 2, 2011

Study Record Updates

• Last Update Posted (Estimate): April 1, 2015
• Last Update Submitted That Met QC Criteria: March 18, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Asthma; QAB149; Indacaterol
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Maleic acid
• Other Study ID Numbers: CIDD001A2201; 2011-001825-25 (EudraCT Number)