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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01484197
First received: November 15, 2011
Last updated: October 10, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: 75 µg indacaterol maleate (LB)
Drug: 75 µg indacaterol maleate (PoS)
Drug: 37.5 µg indacaterol maleate (PoS)
Drug: placebo to indacaterol (LB)
Drug: placebo to indacaterol (PoS)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Trough Forced Expiratory Volume in One Second (FEV1) After 7 Days of Treatment [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Trough Forced Expiratory Volume in One Second (FEV1) After 1 Day of Treatment [ Time Frame: Day 2 ] [ Designated as safety issue: No ]
    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.

  • Peak Forced Expiratory Volume in One Second (FEV1) at Day 1 and Day 7 [ Time Frame: 0, 0.15, 0.30, 1,2,3,4,8,12 hours on Days 1 and 7 ] [ Designated as safety issue: No ]
    Spirometry was performed according to internationally accepted standards at 0, 0.15, 0.30, 1,2,3,4,8,12 hours on Days 1 and 7. Peak FEV1 was the maximum FEV1 post treatment on Day 1. Analysis of Covariance with treatment, period, sequence and subject nested within sequence as fixed effects and period FEV1 baseline included as a covariate.

  • Time to Peak Forced Expiratory Volume in One Second (FEV1) at Day 1 and Day 7 [ Time Frame: 0, 0.15, 0.30, 1,2,3,4,8,12 hours on Days 1 and 7 ] [ Designated as safety issue: No ]
    Spirometry was performed according to internationally accepted standards. Time to the peak (maximum) FEV1 was recorded at 0, 0.15, 0.30, 1,2,3,4,8,12 hours on Days 1 and 7. Analysis of Covariance with treatment, period, sequence and subject nested within sequence as fixed effects and period FEV1 baseline as a covariate.

  • Forced Expiratory Volume in One Second (FEV1) at Each Time-Point on Day 1 and Day 2 [ Time Frame: 0, 0.5 and 0.30, 1, 2, 3, 4, 8 hours, on Day 1 and 23.16 and 23.75 hours on Day 2 ] [ Designated as safety issue: No ]
    Spirometry was conducted according to internationally accepted standards post-dose at 0, 0.5 and 0.30, 1, 2, 3, 4, 8 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.

  • FEV1 at Each Time-Point on Day 7 and Day 8 [ Time Frame: 0, 0.15, 0.30, 1,2,3,4,8,12 hours on Day 7 and 23.16 and 23.75 hours on Day 8. ] [ Designated as safety issue: No ]
    Spirometry was conducted according to internationally accepted standards at 0, 0.15, 0.30, 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.

  • Forced Vital Capacity (FVC) at Each Time-Point on Day 1 and Day 2 [ Time Frame: 0, 0.15, 0.30, 1,2,3,4,8,12 hours on Day 1 and 23.16 and 23.75 hours on Day 2 ] [ Designated as safety issue: No ]
    Spirometry was conducted according to internationally accepted standards post-dose at 0, 0.15, 0.30, 1,2,3,4,8,12 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.

  • Forced Vital Capacity (FVC) at Each Time-Point on Day 7 and Day 8 [ Time Frame: 0, 0.15, 0.30, 1,2,3,4,8,12 hours on Day 7 and 23.16 and 23.75 hours on Day 8 ] [ Designated as safety issue: No ]
    Spirometry was conducted according to internationally accepted standards post-dose at 0, 0.15, 0.30, 1,2,3,4,8,12 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.

  • FEV1/FVC at Each Post-Dose Time Point on Day 1 and Day 2 [ Time Frame: 0, 0.15, 0.30, 1,2,3,4,8,12 hours on Day 1 and 23.16 and 23.75 hours on Day 2 ] [ Designated as safety issue: No ]
    Spirometry was conducted according to internationally accepted standards post-dose at 0, 0.15, 0.30, 1,2,3,4,8,12 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.

  • FEV1/FVC at Each Post-dose Time Point on Day 7 and Day 8 [ Time Frame: 0, 0.15, 0.30, 1,2,3,4,8,12 hours on Day 7 and 23.16 and 23.75 hours on Day 8 ] [ Designated as safety issue: No ]
    Spirometry was conducted according to internationally accepted standards post-dose at 0, 0.15, 0.30, 1,2,3,4,8,12 hours on Day 7 and 23.16 and 23.75 hours on Day 8 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.

  • Forced Expiratory Flow 25- 75% (FEF25-75) on Day 1 and Day 2 [ Time Frame: 0, 0.15, 0.30, 1,2,3,4,8,12 hours on Day 1 and 23.16 and 23.75 hours on Day 2 ] [ Designated as safety issue: No ]
    Spirometry was conducted according to internationally accepted standards post-dose at 0, 0.15, 0.30, 1,2,3,4,8,12 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.

  • Forced Expiratory Flow 25- 75% (FEF25-75) on Day 7 and Day 8 [ Time Frame: 0, 0.15, 0.30, 1,2,3,4,8,12 hours on Day 7 and 23.16 and 23.75 hours on Day 8 ] [ Designated as safety issue: No ]
    Spirometry was conducted according to internationally accepted standards post-dose at 0, 0.15, 0.30, 1,2,3,4,8,12 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.

  • Standardized FEV1 AUC Between Baseline (Pre-dose) and 4 Hour Post-dose (AUC0-4h) [ Time Frame: Day 1, Day 7 ] [ Designated as safety issue: No ]
    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.

  • Standardized FEV1 AUC Between Baseline (Pre-dose) and 12 Hour Post-dose (AUC0-12h) [ Time Frame: Day 1, Day 7 ] [ Designated as safety issue: No ]
    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.

  • Peak Expiratory Flow Rate in the Morning in the Evening [ Time Frame: Up to 101 days ] [ Designated as safety issue: No ]
    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.

  • Number of Puffs of Rescue Medicine [ Time Frame: Up to 101 days ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Adverse Events as a Measure of Safety [ Time Frame: Up to 101 days ] [ Designated as safety issue: Yes ]
    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

  • Time to Reach Maximum Concentration (Tmax) After Drug Administration [ Time Frame: Day1, Day 7 ] [ Designated as safety issue: No ]
  • Observed Maximum Concentration (Cmax) After Drug Administration [ Time Frame: Day 1, Day 7 ] [ Designated as safety issue: No ]
  • Area Under the Curve Pre-dose to 24 Hour Post Dose (AUC0-24h) [ Time Frame: Day 1, Day 7 ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: November 2011
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 75 µg indacaterol (LB) + Placebo (PoS)
75 µg indacaterol maleate lactose blend (LB) + placebo to indacaterol 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 indacaterol 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: 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.
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: 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 (LB)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 Forced Expiratory Volume in one second (FEV1) after inhaling a short acting beta agonist

Exclusion Criteria:

  • Asthma exacerbations in previous 6 months
  • Chronic Obstructive Pulmonary Disease (COPD) or other pulmonary disease
  • Excessive use of short acting beta agonists
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01484197

Locations
Germany
Novartis Investigative Site
Wiesbaden, Germany, D-65187
United Kingdom
Novartis Investigative Site
Machester, United Kingdom, M23 9QZ
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01484197     History of Changes
Other Study ID Numbers: CIDD001A2201, 2011-001825-25
Study First Received: November 15, 2011
Results First Received: May 17, 2013
Last Updated: October 10, 2013
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Asthma
Indacaterol
QAB149

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Maleic acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014