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Pharmacodynamics, Safety, Tolerability, and Pharmacokinetics of Two Orally Inhaled Indacaterol Salts in Adult Subjects With Asthma.

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03257995
Collaborator
(none)
54
Enrollment
6
Locations
6
Arms
4.4
Actual Duration (Months)
9
Patients Per Site
2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a randomized, double-blind, placebo-controlled, three-period cross-over study in approximately 54 subjects with asthma.

Condition or Disease Intervention/Treatment Phase
  • Drug: Indacaterol maleate
  • Drug: Indacaterol acetate
  • Drug: Placebo
 Phase 2

Detailed Description

This is a randomized, double-blind, placebo-controlled, three-period cross-over study in asthma patients. The study will consist of a screening epoch, followed by a treatment epoch which consists of three treatment periods, and will conclude with an end of study epoch.

Each subject will be assigned to 1 of 6 treatment sequences and will sequentially receive the investigational products and placebo during the trial.

Study Design

Study Type:
Interventional
Actual Enrollment :
54 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled, Three-period Cross-over Study to Assess the Pharmacodynamics, Safety, Tolerability, and Pharmacokinetics of Two Orally Inhaled Indacaterol Salts (Maleate and Acetate) Delivered Via the Concept1 Inhalation Device in Patients With Asthma
Actual Study Start Date :
Sep 5, 2017
Actual Primary Completion Date :
Jan 17, 2018
Actual Study Completion Date :
Jan 18, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Sequence 1

A-B-C

Drug: Indacaterol maleate
150 μg via Concept1 device
Other Names:
  • A

    • Drug: Indacaterol acetate
    150 μg via Concept1 device
    Other Names:
  • B

    • Drug: Placebo
    Capsule containing no active ingredients delivered via Concept1 device
    Other Names:
  • C

    		•
    Experimental: Sequence 2

    B-C-A

    Drug: Indacaterol maleate
    150 μg via Concept1 device
    Other Names:
  • A

    • Drug: Indacaterol acetate
    150 μg via Concept1 device
    Other Names:
  • B

    • Drug: Placebo
    Capsule containing no active ingredients delivered via Concept1 device
    Other Names:
  • C

    		•
    Experimental: Sequence 3

    C-A-B

    Drug: Indacaterol maleate
    150 μg via Concept1 device
    Other Names:
  • A

    • Drug: Indacaterol acetate
    150 μg via Concept1 device
    Other Names:
  • B

    • Drug: Placebo
    Capsule containing no active ingredients delivered via Concept1 device
    Other Names:
  • C

    		•
    Experimental: Sequence 4

    A-C-B

    Drug: Indacaterol maleate
    150 μg via Concept1 device
    Other Names:
  • A

    • Drug: Indacaterol acetate
    150 μg via Concept1 device
    Other Names:
  • B

    • Drug: Placebo
    Capsule containing no active ingredients delivered via Concept1 device
    Other Names:
  • C

    		•
    Experimental: Sequence 5

    B-A-C

    Drug: Indacaterol maleate
    150 μg via Concept1 device
    Other Names:
  • A

    • Drug: Indacaterol acetate
    150 μg via Concept1 device
    Other Names:
  • B

    • Drug: Placebo
    Capsule containing no active ingredients delivered via Concept1 device
    Other Names:
  • C

    		•
    Experimental: Sequence 6

    C-B-A

    Drug: Indacaterol maleate
    150 μg via Concept1 device
    Other Names:
  • A

    • Drug: Indacaterol acetate
    150 μg via Concept1 device
    Other Names:
  • B

    • Drug: Placebo
    Capsule containing no active ingredients delivered via Concept1 device
    Other Names:
  • C

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Trough FEV1 [Day 14 of each of the three treatment periods]

      FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of forced exhalation. Treatment differences in trough FEV1 after 14 days of treatment between indacaterol maleate 150 μg and placebo, between indacaterol acetate 150 μg and placebo and indacaterol maleate and indacaterol acetate

    Secondary Outcome Measures

    1. Pharmacokinetics AUC 0-24hours at Steady State [Day 14 of each of the three treatment periods]

      AUC 0-24hours of plasma concentrations of indacaterol maleate and indacaterol acetate at steady state.The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration in the blood samplings

    2. The Maximum Concentration (Cmax) at Steady State (ss) [Day 14 of each of the three treatment periods]

      Maximal plasma concentrations of indacaterol maleate and indacaterol acetate at steady state. The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration in the blood samplings.

    3. Time of Maximal Plasma Concentration (Tmax) at Steady State [Day 14 of each of the three treatment periods]

      Time of maximal plasma concentration of indacaterol maleate and indacaterol acetate at steady state. Time to reach the maximum concentration after administration. In this analysis Tmax will be reported using blood samples taken on Days 14

    4. The Lowest Plasma (or Serum or Blood) Concentration (Cmin) at Steady State [Day 14 of each of the three treatment periods]

      The lowest plasma (or serum or blood) concentration observed during a dosing interval at steady state. Only summary statistics was provided.

    5. Relative Bioavailability (Frel) of Indacaterol Acetate and Indacaterol Maleate [Day 14]

      Relative bioavailability will be determined for AUC0-24h,ss and Cmax,ss comparing systemic exposure of indacaterol acetate and indacaterol maleate.

    6. Time to Peak FEV1 on Day 14 [Day 14 of each of the three treatment periods]

      The differences in median time to peak FEV1 (h) between indacaterol maleate 150 µg and placebo

    7. Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints [Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min]

      Bronchodilator effect of indacaterol salts compared to placebo in terms of FEV1. Day 14, FEV1 was measured at 24hours post dose

    8. Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints [Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min]

      The FEV1 percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 % predicted indicates improvement in lung function. FEV1 % predicted was assessed at each post dose time point after 14 days

    9. Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC) [Day 14 of each of the three treatment periods at at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min]

      Forced Vital Capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed by spirometry at each post dose time point after 14 days. A positive change from baseline in FVC indicates improvement in lung function.

    10. Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted) [Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min]

      Forced Vital Capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed by spirometry at each post dose time point after 14 days. A positive change from baseline in FVC indicates improvement in lung function.

    11. Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC [Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min]

      Bronchodilator effect of indacaterol salts compared to placebo in terms of FEV1/FVC at each post dose time point after 14 days. FEV1/FVC ratio is the percentage of the total FVC that is expelled from the lungs during the first second of forced exhalation.

    12. Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75% [Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min]

      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 at each post dose time point after 14 days

    13. Bronchodilator Effect of Indacaterol Salts Compared to Placebo in Standardized FEV1 AUC. [Pre-dose to 4 hours post-dose on Day 14 of each of the three treatment periods]

      Standardized FEV1 AUC from pre-dose to 4 h post-dose. Evaluated the differences in standardized FEV1 AUC0-4h (L) after 14 days of treatment between indacaterol maleate 150 μg and placebo, and between indacaterol acetate 150 μg and placebo. FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 0-4h)

    14. Rescue Medication Usage [14 days of treatment for each of the three treatment periods]

      The mean daily number of puffs of rescue medication usage as reported by subjects via diary.

    15. Mean Overall Peak Expiratory Flow (PEF) [Days 8 through Day 14 of each of the three treatment periods]

      A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits LS Mean of change from baseline in mean morning PEF is calculated with the ANOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Male and female patients aged ≥ 18 and above

    • Patients with a documented physician diagnosis of asthma for a period of at least 1 year prior to screening and who additionally meet the following criteria:

    Patients receiving daily treatment with an inhaled corticosteroid up to the maximum dose per day (as indicated in the package leaflet), on a stable regimen for at least 4 weeks prior to screening.

    • Pre-bronchodilator FEV1 ≥ 50 % and ≤ 90% of the predicted normal value for the patient during screening.

    • Patients who demonstrate an increase in FEV1 of ≥ 12% and ≥ 200 mL after administration of 400 μg salbutamol/360 μg albuterol (or equivalent dose) at screening.

    • Subjects must weigh at least 50 kg at screening to participate in the study, and must have a body mass index (BMI) within the range of 18 to 40 kg/m2.

    Key Exclusion Criteria:

    -Contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs, drugs of a similar class, or any component thereof: Sympathomimetic amines / adrenoceptor agonist agents Lactose or any of the other excipients of the study drug (including patients with history of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption)

    • Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of screening.

    • Patients who have had a respiratory tract infection or asthma worsening within 4 weeks prior to screening.

    • Patients with a history of chronic lung diseases other than asthma

    • Patients who have a decline in PEF from the reference PEF (taken at screening) of ≥30% for 5 of 6 consecutive scheduled PEF readings (readings taken at morning and evening) during at least 3 days of screening epoch prior to randomization.

    • Patients who require the use of ≥12 puffs / 24 hours of rescue medication for 48 hours (over two consecutive days) during screening prior to randomization.

    • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

    • Patients with Type I diabetes or uncontrolled Type II diabetes (HbA1c > 9%) at screening.

    • Current smokers (urine cotinine > than the laboratory's lowest level of quantification (LoQ of 500 ng/mL or lower)) and patients who have smoked or inhaled tobacco products within the 6 month period prior to screening, or who have a smoking history of greater than 10 pack years (Note: 1 pack is equivalent to 20 cigarettes. 10 pack years = 1 pack /day x 10 yrs., or ½ pack/day x 20 yrs.).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site North Dartmouth Massachusetts United States 02747-3322
    2 Novartis Investigative Site Saint Louis Missouri United States 63141
    3 Novartis Investigative Site Skillman New Jersey United States 08558
    4 Novartis Investigative Site Raleigh North Carolina United States 27607
    5 Novartis Investigative Site Medford Oregon United States 97504
    6 Novartis Investigative Site El Paso Texas United States 79903

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03257995
    Other Study ID Numbers:
    • CQVM149B2203
    First Posted:
    Aug 22, 2017
    Last Update Posted:
    Jan 5, 2021
    Last Verified:
    Mar 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    asthma, asthma attack, difficulty breathing, bronchial diseases, lung, lung diseases, inhaled drugs, bronchodilator, inhaled corticosteriod
    Additional relevant MeSH terms:
    Asthma
    Maleic acid

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Sequence 4 Sequence 5 Sequence 6
    Arm/Group Description indacaterol maleate 150 μg , indacaterol acetate 150 μg and matching placebo indacaterol acetate 150 μg, matching placebo and indacaterol maleate 150 μg Placebo, indacaterol maleate 150 μg and indacaterol acetate 150 μg indacaterol maleate 150 μg, placebo, and indacaterol acetate 150 μg indacaterol acetate 150 μg, indacaterol maleate 150 μg, and placebo Placebo, indacaterol acetate 150 μg, indacaterol maleate 150 μg
    Period Title: Overall Study
    STARTED 9 9 9 9 9 9
    COMPLETED 9 8 9 9 9 7
    NOT COMPLETED 0 1 0 0 0 2

    Baseline Characteristics

    Arm/Group Title All Participants
    Arm/Group Description All participants randomized to one of six treatment sequences
    Overall Participants 54
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    47.7
    (12.5)
    Sex: Female, Male (Count of Participants)
    Female
    36
    66.7%
    Male
    18
    33.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    7
    13%
    White
    47
    87%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Trough FEV1
    Description FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of forced exhalation. Treatment differences in trough FEV1 after 14 days of treatment between indacaterol maleate 150 μg and placebo, between indacaterol acetate 150 μg and placebo and indacaterol maleate and indacaterol acetate
    Time Frame Day 14 of each of the three treatment periods

    Outcome Measure Data

    Analysis Population Description
    The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
    Arm/Group Title Indacaterol Maleate Indacaterol Acetate Placebo
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler matching placebo capsules to indacaterol via Breezhaler
    Measure Participants 51 52 53
    Mean (Standard Deviation) [Liters]
    2.4173
    (0.78214)
    2.3774
    (0.77679)
    2.2191
    (0.72350)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1861
    Confidence Interval (2-Sided) 95%
    0.1293 to 0.2429
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1463
    Confidence Interval (2-Sided) 95%
    0.0898 to 0.2029
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Indacaterol Acetate
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.0398
    Confidence Interval (2-Sided) 95%
    -0.0942 to 0.0147
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Pharmacokinetics AUC 0-24hours at Steady State
    Description AUC 0-24hours of plasma concentrations of indacaterol maleate and indacaterol acetate at steady state.The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration in the blood samplings
    Time Frame Day 14 of each of the three treatment periods

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all patients with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no major protocol deviations with relevant impact on PK data.
    Arm/Group Title Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler
    Measure Participants 51 52
    Mean (Standard Deviation) [h*pg/mL]
    2300
    (732)
    2050
    (636)
    3. Secondary Outcome
    Title The Maximum Concentration (Cmax) at Steady State (ss)
    Description Maximal plasma concentrations of indacaterol maleate and indacaterol acetate at steady state. The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration in the blood samplings.
    Time Frame Day 14 of each of the three treatment periods

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all patients with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no major protocol deviations with relevant impact on PK data.
    Arm/Group Title Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler
    Measure Participants 51 52
    Median (Full Range) [pg/mL]
    249
    224
    4. Secondary Outcome
    Title Time of Maximal Plasma Concentration (Tmax) at Steady State
    Description Time of maximal plasma concentration of indacaterol maleate and indacaterol acetate at steady state. Time to reach the maximum concentration after administration. In this analysis Tmax will be reported using blood samples taken on Days 14
    Time Frame Day 14 of each of the three treatment periods

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all patients with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no major protocol deviations with relevant impact on PK data.
    Arm/Group Title Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler
    Measure Participants 51 52
    Median (Full Range) [h]
    0.250
    0.467
    5. Secondary Outcome
    Title The Lowest Plasma (or Serum or Blood) Concentration (Cmin) at Steady State
    Description The lowest plasma (or serum or blood) concentration observed during a dosing interval at steady state. Only summary statistics was provided.
    Time Frame Day 14 of each of the three treatment periods

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all patients with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no major protocol deviations with relevant impact on PK data.
    Arm/Group Title Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler
    Measure Participants 51 52
    Median (Full Range) [pg/mL]
    56
    52.3
    6. Secondary Outcome
    Title Relative Bioavailability (Frel) of Indacaterol Acetate and Indacaterol Maleate
    Description Relative bioavailability will be determined for AUC0-24h,ss and Cmax,ss comparing systemic exposure of indacaterol acetate and indacaterol maleate.
    Time Frame Day 14

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all patients with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no major protocol deviations with relevant impact on PK data. Only summary statistics for relative bioavailability was provided.
    Arm/Group Title Indacaterol Maleate / Indacaterol Acetate Indacaterol Acetate 150 µg
    Arm/Group Description Relative bioavailability of indacaterol acetate compared to indacaterol maleate (Frel) AUC0-24h,ss Relative bioavailability of indacaterol acetate compared to indacaterol maleate (Frel) Cmax,ss
    Measure Participants 43 45
    Mean (Standard Deviation) [Ratio]
    0.912
    (0.201)
    0.910
    (0.242)
    7. Secondary Outcome
    Title Time to Peak FEV1 on Day 14
    Description The differences in median time to peak FEV1 (h) between indacaterol maleate 150 µg and placebo
    Time Frame Day 14 of each of the three treatment periods

    Outcome Measure Data

    Analysis Population Description
    The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
    Arm/Group Title Indacaterol Maleate Indacaterol Acetate Placebo
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler matching placebo capsules to indacaterol via Breezhaler
    Measure Participants 51 51 51
    Median (95% Confidence Interval) [h]
    -0.02
    -0.02
    0.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.823
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Method of Estimation Estimation Parameter Median Difference (Final Values)
    Estimated Value -0.02
    Confidence Interval (2-Sided) 95%
    -0.83 to 0.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.801
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Method of Estimation Estimation Parameter Median Difference (Final Values)
    Estimated Value -0.02
    Confidence Interval (2-Sided) 95%
    -0.82 to 0.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.984
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Method of Estimation Estimation Parameter Median Difference (Final Values)
    Estimated Value 0.00
    Confidence Interval (2-Sided) 95%
    -0.50 to 0.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
    Description Bronchodilator effect of indacaterol salts compared to placebo in terms of FEV1. Day 14, FEV1 was measured at 24hours post dose
    Time Frame Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min

    Outcome Measure Data

    Analysis Population Description
    The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
    Arm/Group Title Indacaterol Maleate Indacaterol Acetate Placebo
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler matching placebo capsules to indacaterol via Breezhaler
    Measure Participants 51 52 53
    5 min
    2.4795
    2.4813
    2.2617
    15 min
    2.5005
    2.4965
    2.2282
    30 min
    2.5204
    2.5047
    2.2475
    1 hour
    2.5279
    2.5018
    2.2670
    2 hour
    2.5286
    2.5338
    2.2792
    4 hour
    2.5054
    2.5103
    2.2781
    8 hour
    2.4668
    2.4596
    2.2272
    12 hour
    2.4222
    2.3836
    2.1779
    23 hour 15 min
    2.4678
    2.4022
    2.2398
    23 hour 45 min
    2.4585
    2.4424
    2.2631
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments at 5 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2177
    Confidence Interval (2-Sided) 95%
    0.1482 to 0.2872
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 15min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2724
    Confidence Interval (2-Sided) 95%
    0.2030 to 0.3417
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 30 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2730
    Confidence Interval (2-Sided) 95%
    0.2036 to 0.3423
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 1 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2609
    Confidence Interval (2-Sided) 95%
    0.1915 to 0.3302
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 2 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2494
    Confidence Interval (2-Sided) 95%
    0.1800 to 0.3188
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 4 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2273
    Confidence Interval (2-Sided) 95%
    0.1578 to 0.2968
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 8 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2396
    Confidence Interval (2-Sided) 95%
    0.1697 to 0.3096
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 12 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2443
    Confidence Interval (2-Sided) 95%
    0.1742 to 0.3144
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 23 hour 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2280
    Confidence Interval (2-Sided) 95%
    0.1563 to 0.2997
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 23 hour 45 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1954
    Confidence Interval (2-Sided) 95%
    0.1237 to 0.2671
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 5 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2195
    Confidence Interval (2-Sided) 95%
    0.1502 to 0.2889
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2684
    Confidence Interval (2-Sided) 95%
    0.1988 to 0.3380
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 30 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2572
    Confidence Interval (2-Sided) 95%
    0.1879 to 0.3266
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 1 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2348
    Confidence Interval (2-Sided) 95%
    0.1656 to 0.3040
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 2 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2546
    Confidence Interval (2-Sided) 95%
    0.1852 to 0.3239
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 4 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2322
    Confidence Interval (2-Sided) 95%
    0.1627 to 0.3017
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 8 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2324
    Confidence Interval (2-Sided) 95%
    0.1627 to 0.3020
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 12 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2057
    Confidence Interval (2-Sided) 95%
    0.1359 to 0.2755
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 23 hour 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1625
    Confidence Interval (2-Sided) 95%
    0.0912 to 0.2337
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 23 hour 45 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1793
    Confidence Interval (2-Sided) 95%
    0.1080 to 0.2505
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
    Description The FEV1 percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 % predicted indicates improvement in lung function. FEV1 % predicted was assessed at each post dose time point after 14 days
    Time Frame Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min

    Outcome Measure Data

    Analysis Population Description
    The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
    Arm/Group Title Indacaterol Maleate Indacaterol Acetate Placebo
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler matching placebo capsules to indacaterol via Breezhaler
    Measure Participants 51 52 53
    5 min
    78.2
    78.2
    71.1
    15 min
    78.7
    78.5
    70.2
    30 min
    79.4
    78.9
    70.7
    1 hour
    79.5
    78.8
    71.4
    2 hours
    79.6
    79.8
    72.0
    4 hours
    78.8
    79.1
    71.8
    8 hours
    77.5
    77.5
    70.2
    12 hours
    76.2
    75.0
    68.6
    23 hours 15 min
    77.9
    76.1
    71.0
    23 hours 45 min
    77.8
    77.2
    71.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments at 5 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.1
    Confidence Interval (2-Sided) 95%
    5.0 to 9.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments at 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.5
    Confidence Interval (2-Sided) 95%
    6.4 to 10.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments at 30
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.6
    Confidence Interval (2-Sided) 95%
    6.5 to 10.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments at 1 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.0
    Confidence Interval (2-Sided) 95%
    6.0 to 10.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments at 2 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.6
    Confidence Interval (2-Sided) 95%
    5.5 to 9.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments at 4 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.1
    Confidence Interval (2-Sided) 95%
    5.0 to 9.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments at 8 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.3
    Confidence Interval (2-Sided) 95%
    5.2 to 9.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments at 12 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.6
    Confidence Interval (2-Sided) 95%
    5.5 to 9.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments at 23 hours 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.0
    Confidence Interval (2-Sided) 95%
    4.8 to 9.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments at 23 hours 45 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.4
    Confidence Interval (2-Sided) 95%
    4.2 to 8.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments at 5 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.1
    Confidence Interval (2-Sided) 95%
    5.0 to 9.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments at 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.3
    Confidence Interval (2-Sided) 95%
    6.2 to 10.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments at 30 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.1
    Confidence Interval (2-Sided) 95%
    6.0 to 10.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments at 1 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.4
    Confidence Interval (2-Sided) 95%
    5.3 to 9.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments at 2 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.8
    Confidence Interval (2-Sided) 95%
    5.7 to 9.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments at 4 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.3
    Confidence Interval (2-Sided) 95%
    5.2 to 9.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments at 8 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.4
    Confidence Interval (2-Sided) 95%
    5.3 to 9.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments at 12 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.3
    Confidence Interval (2-Sided) 95%
    4.2 to 8.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments at 23 hours 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.1
    Confidence Interval (2-Sided) 95%
    2.9 to 7.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments at 23 hours 45 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.9
    Confidence Interval (2-Sided) 95%
    3.7 to 8.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
    Description Forced Vital Capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed by spirometry at each post dose time point after 14 days. A positive change from baseline in FVC indicates improvement in lung function.
    Time Frame Day 14 of each of the three treatment periods at at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min

    Outcome Measure Data

    Analysis Population Description
    The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
    Arm/Group Title Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg Placebo
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler matching placebo capsules to indacaterol via Breezhaler
    Measure Participants 51 52 53
    5 min
    3.5648
    3.5912
    3.3783
    15 min
    3.5850
    3.5773
    3.3600
    30 min
    3.6068
    3.6039
    3.3664
    1 hour
    3.5946
    3.5886
    3.3873
    2 hour
    3.5789
    3.5992
    3.3987
    4 hour
    3.5674
    3.5999
    3.4053
    8 hour
    3.5670
    3.5617
    3.3680
    12 hour
    3.4941
    3.4812
    3.3193
    23 hour 15 min
    3.6055
    3.5448
    3.4199
    23 hour 45 min
    3.5668
    3.5731
    3.4185
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 5 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1866
    Confidence Interval (2-Sided) 95%
    0.1121 to 0.2611
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2249
    Confidence Interval (2-Sided) 95%
    0.1506 to 0.2992
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 30 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2404
    Confidence Interval (2-Sided) 95%
    0.1661 to 0.3148
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 1 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2074
    Confidence Interval (2-Sided) 95%
    0.1330 to 0.2817
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 2 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1802
    Confidence Interval (2-Sided) 95%
    0.1059 to 0.2545
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 4 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1621
    Confidence Interval (2-Sided) 95%
    0.0876 to 0.2366
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 8 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1990
    Confidence Interval (2-Sided) 95%
    0.1239 to 0.2742
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 12 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1747
    Confidence Interval (2-Sided) 95%
    0.0994 to 0.2501
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 23 hours 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1856
    Confidence Interval (2-Sided) 95%
    0.1081 to 0.2631
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 23 hours 45 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1484
    Confidence Interval (2-Sided) 95%
    0.0709 to 0.2259
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 5 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2130
    Confidence Interval (2-Sided) 95%
    0.1386 to 0.2873
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2173
    Confidence Interval (2-Sided) 95%
    0.1426 to 0.2920
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 30 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2375
    Confidence Interval (2-Sided) 95%
    0.1632 to 0.3118
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 1 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2013
    Confidence Interval (2-Sided) 95%
    0.1272 to 0.2754
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 2 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2005
    Confidence Interval (2-Sided) 95%
    0.1262 to 0.2749
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 4 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1946
    Confidence Interval (2-Sided) 95%
    0.1201 to 0.2691
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 8 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1937
    Confidence Interval (2-Sided) 95%
    0.1190 to 0.2684
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 12 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1619
    Confidence Interval (2-Sided) 95%
    0.0870 to 0.2369
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 23 hour 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1249
    Confidence Interval (2-Sided) 95%
    0.0480 to 0.2018
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 23 hour 45 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1546
    Confidence Interval (2-Sided) 95%
    0.0777 to 0.2315
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
    Description Forced Vital Capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed by spirometry at each post dose time point after 14 days. A positive change from baseline in FVC indicates improvement in lung function.
    Time Frame Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min

    Outcome Measure Data

    Analysis Population Description
    The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
    Arm/Group Title Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg Placebo
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler matching placebo capsules to indacaterol via Breezhaler
    Measure Participants 51 52 53
    5 min
    90.4
    91.2
    85.3
    15 min
    90.8
    90.7
    84.9
    30 min
    91.6
    91.4
    85.1
    1 hour
    91.1
    91.1
    85.6
    2 hours
    90.7
    91.4
    85.9
    4 hours
    90.5
    91.3
    86.2
    8 hours
    90.4
    90.3
    85.4
    12 hours
    88.5
    88.2
    84
    23 hours 15 min
    91.5
    89.9
    86.9
    23 hours 45 min
    90.6
    90.6
    86.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 5 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5
    Confidence Interval (2-Sided) 95%
    3.1 to 7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6
    Confidence Interval (2-Sided) 95%
    4 to 7.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 30 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.6
    Confidence Interval (2-Sided) 95%
    4.6 to 8.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 1 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.5
    Confidence Interval (2-Sided) 95%
    3.5 to 7.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 2 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.7
    Confidence Interval (2-Sided) 95%
    2.8 to 6.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 4 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.3
    Confidence Interval (2-Sided) 95%
    2.3 to 6.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 8 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5
    Confidence Interval (2-Sided) 95%
    3 to 7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 12 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.5
    Confidence Interval (2-Sided) 95%
    2.5 to 6.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate
    Comments 23 hour 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.6
    Confidence Interval (2-Sided) 95%
    2.6 to 6.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 23 hour 45 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.1
    Confidence Interval (2-Sided) 95%
    2.0 to 6.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 5 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.8
    Confidence Interval (2-Sided) 95%
    3.9 to 7.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.8
    Confidence Interval (2-Sided) 95%
    3.9 to 7.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 30 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.3
    Confidence Interval (2-Sided) 95%
    4.4 to 8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 1 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.5
    Confidence Interval (2-Sided) 95%
    3.5 to 7.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 2 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.5
    Confidence Interval (2-Sided) 95%
    3.5 to 7.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 4 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.0
    Confidence Interval (2-Sided) 95%
    3.1 to 7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 8 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.0
    Confidence Interval (2-Sided) 95%
    3.0 to 7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 12 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.2
    Confidence Interval (2-Sided) 95%
    2.2 to 6.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 23 hour 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.0
    Confidence Interval (2-Sided) 95%
    1.0 to 5.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 23 hour 45 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.1
    Confidence Interval (2-Sided) 95%
    2.1 to 6.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
    Description Bronchodilator effect of indacaterol salts compared to placebo in terms of FEV1/FVC at each post dose time point after 14 days. FEV1/FVC ratio is the percentage of the total FVC that is expelled from the lungs during the first second of forced exhalation.
    Time Frame Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min

    Outcome Measure Data

    Analysis Population Description
    The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
    Arm/Group Title Indacaterol Maleate Indacaterol Acetate Placebo
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler matching placebo capsules to indacaterol via Breezhaler
    Measure Participants 51 52 53
    5 min
    0.6979
    0.6952
    0.6729
    15 min
    0.7002
    0.7017
    0.6672
    30 min
    0.7012
    0.6996
    0.6706
    1 hour
    0.7053
    0.7007
    0.6729
    2 hour
    0.7085
    0.7085
    0.6747
    4 hour
    0.7057
    0.7010
    0.6732
    8 hour
    0.6962
    0.6967
    0.6651
    12 hour
    0.6958
    0.6885
    0.6599
    23 hour 15 min
    0.6898
    0.6853
    0.6572
    23 hour 45 min
    0.6934
    0.6899
    0.6633
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 5 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0249
    Confidence Interval (2-Sided) 95%
    0.0139 to 0.0359
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0330
    Confidence Interval (2-Sided) 95%
    0.0220 to 0.0440
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 30 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0306
    Confidence Interval (2-Sided) 95%
    0.0197 to 0.0416
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 1 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0324
    Confidence Interval (2-Sided) 95%
    0.0214 to 0.0434
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 2 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0338
    Confidence Interval (2-Sided) 95%
    0.0228 to 0.0447
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 4 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0325
    Confidence Interval (2-Sided) 95%
    0.0215 to 0.0435
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 8 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0311
    Confidence Interval (2-Sided) 95%
    0.0200 to 0.0422
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 12 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0359
    Confidence Interval (2-Sided) 95%
    0.0248 to 0.0470
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 23 hour 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0326
    Confidence Interval (2-Sided) 95%
    0.0211 to 0.0440
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 23 hour 45 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0301
    Confidence Interval (2-Sided) 95%
    0.0187 to 0.0415
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 5 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0222
    Confidence Interval (2-Sided) 95%
    0.0113 to 0.0332
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0344
    Confidence Interval (2-Sided) 95%
    0.0234 to 0.0454
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 30 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0290
    Confidence Interval (2-Sided) 95%
    0.0180 to 0.0399
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 1 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0278
    Confidence Interval (2-Sided) 95%
    0.0169 to 0.0387
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 2 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0338
    Confidence Interval (2-Sided) 95%
    0.0228 to 0.0447
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 4 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0278
    Confidence Interval (2-Sided) 95%
    0.0168 to 0.0387
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 8 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0316
    Confidence Interval (2-Sided) 95%
    0.0206 to 0.0426
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 12 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0285
    Confidence Interval (2-Sided) 95%
    0.0175 to 0.0396
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 23 hour 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0281
    Confidence Interval (2-Sided) 95%
    0.0167 to 0.0394
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 23 hour 45 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0266
    Confidence Interval (2-Sided) 95%
    0.0152 to 0.0379
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Secondary Outcome
    Title Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
    Description 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 at each post dose time point after 14 days
    Time Frame Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min

    Outcome Measure Data

    Analysis Population Description
    The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
    Arm/Group Title Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg Placebo
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler matching placebo capsules to indacaterol via Breezhaler
    Measure Participants 51 52 53
    5 min
    1.6968
    1.6918
    1.4962
    15 min
    1.7454
    1.7458
    1.4531
    30 min
    1.7347
    1.7413
    1.4690
    1 hour
    1.7715
    1.7349
    1.4963
    2 hour
    1.7907
    1.8074
    1.5088
    4 hour
    1.7663
    1.7503
    1.4843
    8 hour
    1.6755
    1.6774
    1.4217
    12 hour
    1.6549
    1.5849
    1.3862
    23 hour 15 min
    1.6667
    1.6257
    1.4214
    23 hour 45 min
    1.6446
    1.6580
    1.4584
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 5 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2025
    Confidence Interval (2-Sided) 95%
    0.1059 to 0.2952
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2923
    Confidence Interval (2-Sided) 95%
    0.1979 to 0.3867
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 30 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2657
    Confidence Interval (2-Sided) 95%
    0.1713 to 0.3601
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 1 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2752
    Confidence Interval (2-Sided) 95%
    0.1808 to 0.3696
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 2 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2819
    Confidence Interval (2-Sided) 95%
    0.1875 to 0.3763
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 4 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2820
    Confidence Interval (2-Sided) 95%
    0.1874 to 0.3766
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 8 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2538
    Confidence Interval (2-Sided) 95%
    0.1585 to 0.3492
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 12 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2687
    Confidence Interval (2-Sided) 95%
    0.1732 to 0.3643
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 23 hours 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2453
    Confidence Interval (2-Sided) 95%
    0.1473 to 0.3434
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments 23 hours 45 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1862
    Confidence Interval (2-Sided) 95%
    0.0882 to 0.2842
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 5 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1956
    Confidence Interval (2-Sided) 95%
    0.1012 to 0.2899
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2927
    Confidence Interval (2-Sided) 95%
    0.1979 to 0.3875
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 30 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2723
    Confidence Interval (2-Sided) 95%
    0.1780 to 0.3667
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 1 hour
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2386
    Confidence Interval (2-Sided) 95%
    0.1445 to 0.3328
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 2 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2986
    Confidence Interval (2-Sided) 95%
    0.2042 to 0.3930
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 4 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2661
    Confidence Interval (2-Sided) 95%
    0.1715 to 0.3607
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 8 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2558
    Confidence Interval (2-Sided) 95%
    0.1609 to 0.3506
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 12 hours
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1987
    Confidence Interval (2-Sided) 95%
    0.1036 to 0.2938
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 23 hours 15 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2044
    Confidence Interval (2-Sided) 95%
    0.1071 to 0.3017
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments 23 hours 45 min
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.1997
    Confidence Interval (2-Sided) 95%
    0.1023 to 0.2970
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title Bronchodilator Effect of Indacaterol Salts Compared to Placebo in Standardized FEV1 AUC.
    Description Standardized FEV1 AUC from pre-dose to 4 h post-dose. Evaluated the differences in standardized FEV1 AUC0-4h (L) after 14 days of treatment between indacaterol maleate 150 μg and placebo, and between indacaterol acetate 150 μg and placebo. FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 0-4h)
    Time Frame Pre-dose to 4 hours post-dose on Day 14 of each of the three treatment periods

    Outcome Measure Data

    Analysis Population Description
    The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
    Arm/Group Title Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg Placebo
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler matching placebo capsules to indacaterol via Breezhaler
    Measure Participants 51 52 51
    Least Squares Mean (Standard Error) [Liters]
    2.5179
    (0.11213)
    2.5151
    (0.11205)
    2.2703
    (0.11213)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2476
    Confidence Interval (2-Sided) 95%
    0.1857 to 0.3095
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2448
    Confidence Interval (2-Sided) 95%
    0.1830 to 0.3066
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Indacaterol Acetate
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.0028
    Confidence Interval (2-Sided) 95%
    -0.0647 to 0.0590
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Secondary Outcome
    Title Rescue Medication Usage
    Description The mean daily number of puffs of rescue medication usage as reported by subjects via diary.
    Time Frame 14 days of treatment for each of the three treatment periods

    Outcome Measure Data

    Analysis Population Description
    The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
    Arm/Group Title Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg Placebo
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler matching placebo capsules to indacaterol via Breezhaler
    Measure Participants 51 52 51
    Least Squares Mean (Standard Error) [Puffs]
    1.01
    (0.228)
    1.01
    (0.227)
    1.43
    (0.228)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.42
    Confidence Interval (2-Sided) 95%
    -0.73 to 0.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.42
    Confidence Interval (2-Sided) 95%
    -0.73 to 0.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    16. Secondary Outcome
    Title Mean Overall Peak Expiratory Flow (PEF)
    Description A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits LS Mean of change from baseline in mean morning PEF is calculated with the ANOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates
    Time Frame Days 8 through Day 14 of each of the three treatment periods

    Outcome Measure Data

    Analysis Population Description
    The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
    Arm/Group Title Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg Placebo
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler matching placebo capsules to indacaterol via Breezhaler
    Measure Participants 51 52 51
    Least Squares Mean (Standard Error) [Liters/min]
    409.7
    (15.06)
    407.6
    (15.05)
    376.8
    (15.06)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Indacaterol Maleate, Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 33.0
    Confidence Interval (2-Sided) 95%
    25.6 to 40.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Indacaterol Acetate, Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 30.8
    Confidence Interval (2-Sided) 95%
    23.5 to 38.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame until 30 days after the last Investigational Product (IP) administration
    Adverse Event Reporting Description
    Arm/Group Title Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg Placebo
    Arm/Group Description indacaterol maleate 150 μg via Breezhaler indacaterol acetate 150 μg via Breezhaler matching placebo capsules to indacaterol via Breezhaler
    All Cause Mortality
    Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/51 (0%) 0/52 (0%) 0/53 (0%)
    Serious Adverse Events
    Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/51 (0%) 1/52 (1.9%) 0/53 (0%)
    Infections and infestations
    Pharyngitis streptococcal 0/51 (0%) 1/52 (1.9%) 0/53 (0%)
    Sinusitis 0/51 (0%) 1/52 (1.9%) 0/53 (0%)
    Other (Not Including Serious) Adverse Events
    Indacaterol Maleate 150 µg Indacaterol Acetate 150 µg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/51 (27.5%) 7/52 (13.5%) 9/53 (17%)
    Gastrointestinal disorders
    Nausea 0/51 (0%) 1/52 (1.9%) 0/53 (0%)
    Vomiting 1/51 (2%) 1/52 (1.9%) 0/53 (0%)
    Hepatobiliary disorders
    Cholangitis 0/51 (0%) 0/52 (0%) 1/53 (1.9%)
    Infections and infestations
    Nasopharyngitis 0/51 (0%) 0/52 (0%) 1/53 (1.9%)
    Sinusitis 0/51 (0%) 0/52 (0%) 1/53 (1.9%)
    Upper respiratory tract infection 1/51 (2%) 2/52 (3.8%) 2/53 (3.8%)
    Injury, poisoning and procedural complications
    Laceration 0/51 (0%) 0/52 (0%) 1/53 (1.9%)
    Skin abrasion 0/51 (0%) 0/52 (0%) 1/53 (1.9%)
    Investigations
    Alanine aminotransferase increased 0/51 (0%) 1/52 (1.9%) 0/53 (0%)
    Aspartate aminotransferase increased 0/51 (0%) 1/52 (1.9%) 0/53 (0%)
    Blood potassium increased 1/51 (2%) 0/52 (0%) 0/53 (0%)
    Weight increased 0/51 (0%) 1/52 (1.9%) 0/53 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/51 (0%) 1/52 (1.9%) 1/53 (1.9%)
    Back pain 0/51 (0%) 1/52 (1.9%) 0/53 (0%)
    Muscle spasms 0/51 (0%) 1/52 (1.9%) 0/53 (0%)
    Pain in extremity 0/51 (0%) 0/52 (0%) 1/53 (1.9%)
    Nervous system disorders
    Dizziness 1/51 (2%) 0/52 (0%) 0/53 (0%)
    Headache 0/51 (0%) 1/52 (1.9%) 0/53 (0%)
    Psychiatric disorders
    Anxiety 0/51 (0%) 1/52 (1.9%) 0/53 (0%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/51 (0%) 1/52 (1.9%) 0/53 (0%)
    Cough 12/51 (23.5%) 0/52 (0%) 1/53 (1.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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 or disclosure of trial results in their entirety

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email novartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03257995
    Other Study ID Numbers:
    • CQVM149B2203
    First Posted:
    Aug 22, 2017
    Last Update Posted:
    Jan 5, 2021
    Last Verified:
    Mar 1, 2019