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CompletedNCT03257995Updated Jan 5, 2021Results posted

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

A Phase 2 interventional study of Indacaterol maleate and Indacaterol acetate in Asthma, sponsored by Novartis Pharmaceuticals. Completed at 6 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-01-05.

Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
54
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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

Read the 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.

02

Conditions studied

  • Asthma

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Keywords

  • asthma, asthma attack, difficulty breathing, bronchial diseases, lung, lung diseases, inhaled drugs, bronchodilator, inhaled corticosteriod
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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.).
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
54 participants (actual)

Study arms

  • Experimental
    Sequence 1

    A-B-C

    Drug: Indacaterol maleate · Drug: Indacaterol acetate · Drug: Placebo

  • Experimental
    Sequence 2

    B-C-A

    Drug: Indacaterol maleate · Drug: Indacaterol acetate · Drug: Placebo

  • Experimental
    Sequence 3

    C-A-B

    Drug: Indacaterol maleate · Drug: Indacaterol acetate · Drug: Placebo

  • Experimental
    Sequence 4

    A-C-B

    Drug: Indacaterol maleate · Drug: Indacaterol acetate · Drug: Placebo

  • Experimental
    Sequence 5

    B-A-C

    Drug: Indacaterol maleate · Drug: Indacaterol acetate · Drug: Placebo

  • Experimental
    Sequence 6

    C-B-A

    Drug: Indacaterol maleate · Drug: Indacaterol acetate · Drug: Placebo

Interventions

  • DrugIndacaterol maleate

    150 μg via Concept1 device

    Also known as: A

  • DrugIndacaterol acetate

    150 μg via Concept1 device

    Also known as: B

  • DrugPlacebo

    Capsule containing no active ingredients delivered via Concept1 device

    Also known as: C

05

What researchers measure

Primary outcomes

  1. Trough FEV1

    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

Secondary outcomes

  1. Pharmacokinetics AUC 0-24hours at Steady State

    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

  2. The Maximum Concentration (Cmax) at Steady State (ss)

    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

  3. Time of Maximal Plasma Concentration (Tmax) at Steady State

    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

  4. The Lowest Plasma (or Serum or Blood) Concentration (Cmin) at Steady State

    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

  5. Relative Bioavailability (Frel) of Indacaterol Acetate and Indacaterol Maleate

    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

  6. Time to Peak FEV1 on Day 14

    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

  7. Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints

    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

  8. Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints

    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

  9. Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)

    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

  10. Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)

    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

  11. Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC

    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

  12. Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%

    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

  13. Bronchodilator Effect of Indacaterol Salts Compared to Placebo in Standardized FEV1 AUC.

    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

  14. Rescue Medication Usage

    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

  15. Mean Overall Peak Expiratory Flow (PEF)

    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

06

Results

Posted Mar 29, 2019

Participant flow

Participant flow — Overall Study
MilestoneSequence 1Sequence 2Sequence 3Sequence 4Sequence 5Sequence 6
Started999999
Completed989997
Not completed010002
Withdrew: Adverse event010000
Withdrew: Protocol deviation000002

Outcome measures

PrimaryTrough FEV1

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
Reported as:
Mean · Liters
Trough FEV1
LitersIndacaterol MaleateIndacaterol AcetatePlacebo
Trough FEV12.4173 ± 0.782142.3774 ± 0.776792.2191 ± 0.72350
Statistical analysis
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1861 · 95% CI 0.1293 to 0.2429
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1463 · 95% CI 0.0898 to 0.2029
  • Indacaterol Maleate vs Indacaterol Acetate · ANOVA · Mean difference (final values): -0.0398 · 95% CI -0.0942 to 0.0147
SecondaryPharmacokinetics AUC 0-24hours at Steady State

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
Reported as:
Mean · h*pg/mL
Pharmacokinetics AUC 0-24hours at Steady State
h*pg/mLIndacaterol Maleate 150 µgIndacaterol Acetate 150 µg
Pharmacokinetics AUC 0-24hours at Steady State2300 ± 7322050 ± 636
SecondaryThe Maximum Concentration (Cmax) at Steady State (ss)

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
Reported as:
Median · pg/mL
The Maximum Concentration (Cmax) at Steady State (ss)
pg/mLIndacaterol Maleate 150 µgIndacaterol Acetate 150 µg
The Maximum Concentration (Cmax) at Steady State (ss)249 (126 to 443)224 (84.9 to 426)
SecondaryTime of Maximal Plasma Concentration (Tmax) at Steady State

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
Reported as:
Median · h
Time of Maximal Plasma Concentration (Tmax) at Steady State
hIndacaterol Maleate 150 µgIndacaterol Acetate 150 µg
Time of Maximal Plasma Concentration (Tmax) at Steady State0.250 (0.183 to 0.850)0.467 (0.183 to 1.00)
SecondaryThe Lowest Plasma (or Serum or Blood) Concentration (Cmin) at Steady State

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
Reported as:
Median · pg/mL
The Lowest Plasma (or Serum or Blood) Concentration (Cmin) at Steady State
pg/mLIndacaterol Maleate 150 µgIndacaterol Acetate 150 µg
The Lowest Plasma (or Serum or Blood) Concentration (Cmin) at Steady State56 (14.5 to 126)52.3 (9.03 to 106)
SecondaryRelative Bioavailability (Frel) of Indacaterol Acetate and Indacaterol Maleate

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
Reported as:
Mean · Ratio
Relative Bioavailability (Frel) of Indacaterol Acetate and Indacaterol Maleate
RatioIndacaterol Maleate / Indacaterol AcetateIndacaterol Acetate 150 µg
Relative Bioavailability (Frel) of Indacaterol Acetate and Indacaterol Maleate0.912 ± 0.2010.910 ± 0.242
SecondaryTime to Peak FEV1 on Day 14

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
Reported as:
Median · h
Time to Peak FEV1 on Day 14
hIndacaterol MaleateIndacaterol AcetatePlacebo
Time to Peak FEV1 on Day 14-0.02 (-0.83 to 0.33)-0.02 (-0.82 to 0.51)0.00 (-0.50 to 0.73)
Statistical analysis
  • Indacaterol Maleate · Wilcoxon (Mann-Whitney) · p = 0.823 · Median difference (final values): -0.02 · 95% CI -0.83 to 0.33
  • Indacaterol Acetate · Wilcoxon (Mann-Whitney) · p = 0.801 · Median difference (final values): -0.02 · 95% CI -0.82 to 0.51
  • Placebo · Wilcoxon (Mann-Whitney) · p = 0.984 · Median difference (final values): 0.00 · 95% CI -0.50 to 0.73
SecondaryBronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints

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
Reported as:
Least squares mean · Liter
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
LiterIndacaterol MaleateIndacaterol AcetatePlacebo
5 min2.4795 (2.2575 to 2.7014)2.4813 (2.2595 to 2.7031)2.2617 (2.0398 to 2.4837)
15 min2.5005 (2.2786 to 2.7224)2.4965 (2.2746 to 2.7184)2.2282 (2.0062 to 2.4501)
30 min2.5204 (2.2985 to 2.7424)2.5047 (2.2829 to 2.7265)2.2475 (2.0255 to 2.4694)
1 hour2.5279 (2.3060 to 2.7498)2.5018 (2.2800 to 2.7236)2.2670 (2.0451 to 2.4889)
2 hour2.5286 (2.3067 to 2.7505)2.5338 (2.3120 to 2.7556)2.2792 (2.0573 to 2.5011)
4 hour2.5054 (2.2835 to 2.7273)2.5103 (2.2885 to 2.7321)2.2781 (2.0561 to 2.5001)
8 hour2.4668 (2.2448 to 2.6888)2.4596 (2.2378 to 2.6814)2.2272 (2.0052 to 2.4492)
12 hour2.4222 (2.2002 to 2.6442)2.3836 (2.1618 to 2.6054)2.1779 (1.9558 to 2.3999)
23 hour 15 min2.4678 (2.2457 to 2.6899)2.4022 (2.1804 to 2.6241)2.2398 (2.0173 to 2.4622)
23 hour 45 min2.4585 (2.2364 to 2.6806)2.4424 (2.2205 to 2.6642)2.2631 (2.0407 to 2.4856)
Statistical analysis
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2177 · 95% CI 0.1482 to 0.2872
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2724 · 95% CI 0.2030 to 0.3417
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2730 · 95% CI 0.2036 to 0.3423
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2609 · 95% CI 0.1915 to 0.3302
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2494 · 95% CI 0.1800 to 0.3188
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2273 · 95% CI 0.1578 to 0.2968
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2396 · 95% CI 0.1697 to 0.3096
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2443 · 95% CI 0.1742 to 0.3144
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2280 · 95% CI 0.1563 to 0.2997
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1954 · 95% CI 0.1237 to 0.2671
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2195 · 95% CI 0.1502 to 0.2889
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2684 · 95% CI 0.1988 to 0.3380
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2572 · 95% CI 0.1879 to 0.3266
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2348 · 95% CI 0.1656 to 0.3040
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2546 · 95% CI 0.1852 to 0.3239
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2322 · 95% CI 0.1627 to 0.3017
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2324 · 95% CI 0.1627 to 0.3020
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2057 · 95% CI 0.1359 to 0.2755
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1625 · 95% CI 0.0912 to 0.2337
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1793 · 95% CI 0.1080 to 0.2505
SecondaryPercent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints

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
Reported as:
Least squares mean · Percent of predicted
Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
Percent of predictedIndacaterol MaleateIndacaterol AcetatePlacebo
5 min78.2 (74.7 to 81.7)78.2 (74.8 to 81.7)71.1 (67.7 to 74.6)
15 min78.7 (75.2 to 82.2)78.5 (75.0 to 82.0)70.2 (66.7 to 73.7)
30 min79.4 (75.9 to 82.9)78.9 (75.4 to 82.3)70.7 (67.3 to 74.2)
1 hour79.5 (76.0 to 83.0)78.8 (75.3 to 82.3)71.4 (67.9 to 74.9)
2 hours79.6 (76.1 to 83.1)79.8 (76.3 to 83.2)72.0 (68.5 to 75.5)
4 hours78.8 (75.4 to 82.3)79.1 (75.6 to 82.5)71.8 (68.3 to 75.3)
8 hours77.5 (74.0 to 81.0)77.5 (74.1 to 81.0)70.2 (66.7 to 73.6)
12 hours76.2 (72.7 to 79.7)75.0 (71.5 to 78.5)68.6 (65.2 to 72.1)
23 hours 15 min77.9 (74.5 to 81.4)76.1 (72.6 to 79.5)71.0 (67.5 to 74.5)
23 hours 45 min77.8 (74.3 to 81.3)77.2 (73.7 to 80.7)71.4 (67.8 to 74.9)
Statistical analysis
  • Indacaterol Maleate vs Placebo · ANOVA · p = <.001 · Mean difference (final values): 7.1 · 95% CI 5.0 to 9.2
  • Indacaterol Maleate vs Placebo · ANOVA · p = <.001 · Mean difference (final values): 8.5 · 95% CI 6.4 to 10.6
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 8.6 · 95% CI 6.5 to 10.7
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 8.0 · 95% CI 6.0 to 10.1
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 7.6 · 95% CI 5.5 to 9.7
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 7.1 · 95% CI 5.0 to 9.1
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 7.3 · 95% CI 5.2 to 9.4
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 7.6 · 95% CI 5.5 to 9.7
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 7.0 · 95% CI 4.8 to 9.1
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 6.4 · 95% CI 4.2 to 8.6
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 7.1 · 95% CI 5.0 to 9.2
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 8.3 · 95% CI 6.2 to 10.4
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 8.1 · 95% CI 6.0 to 10.2
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 7.4 · 95% CI 5.3 to 9.4
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 7.8 · 95% CI 5.7 to 9.9
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 7.3 · 95% CI 5.2 to 9.4
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 7.4 · 95% CI 5.3 to 9.5
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 6.3 · 95% CI 4.2 to 8.4
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 5.1 · 95% CI 2.9 to 7.2
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 5.9 · 95% CI 3.7 to 8.0
SecondaryBronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)

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
Reported as:
Least squares mean · liter
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
literIndacaterol Maleate 150 µgIndacaterol Acetate 150 µgPlacebo
5 min3.5648 (3.2407 to 3.8890)3.5912 (3.2672 to 3.9152)3.3783 (3.0541 to 3.7024)
15 min3.5850 (3.2608 to 3.9091)3.5773 (3.2531 to 3.9015)3.3600 (3.0359 to 3.6842)
30 min3.6068 (3.2827 to 3.9310)3.6039 (3.2798 to 3.9279)3.3664 (3.0422 to 3.6905)
1 hour3.5946 (3.2705 to 3.9188)3.5886 (3.2645 to 3.9126)3.3873 (3.0631 to 3.7114)
2 hour3.5789 (3.2548 to 3.9031)3.5992 (3.2751 to 3.9233)3.3987 (3.0745 to 3.7228)
4 hour3.5674 (3.2433 to 3.8916)3.5999 (3.2759 to 3.9240)3.4053 (3.0812 to 3.7295)
8 hour3.5670 (3.2428 to 3.8913)3.5617 (3.2376 to 3.8858)3.3680 (3.0438 to 3.6922)
12 hour3.4941 (3.1698 to 3.8183)3.4812 (3.1571 to 3.8053)3.3193 (2.9950 to 3.6436)
23 hour 15 min3.6055 (3.2812 to 3.9298)3.5448 (3.2207 to 3.8689)3.4199 (3.0952 to 3.7446)
23 hour 45 min3.5668 (3.2425 to 3.8912)3.5731 (3.2489 to 3.8972)3.4185 (3.0938 to 3.7431)
Statistical analysis
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1866 · 95% CI 0.1121 to 0.2611
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2249 · 95% CI 0.1506 to 0.2992
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2404 · 95% CI 0.1661 to 0.3148
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2074 · 95% CI 0.1330 to 0.2817
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1802 · 95% CI 0.1059 to 0.2545
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1621 · 95% CI 0.0876 to 0.2366
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1990 · 95% CI 0.1239 to 0.2742
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1747 · 95% CI 0.0994 to 0.2501
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1856 · 95% CI 0.1081 to 0.2631
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1484 · 95% CI 0.0709 to 0.2259
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2130 · 95% CI 0.1386 to 0.2873
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2173 · 95% CI 0.1426 to 0.2920
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2375 · 95% CI 0.1632 to 0.3118
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2013 · 95% CI 0.1272 to 0.2754
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2005 · 95% CI 0.1262 to 0.2749
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1946 · 95% CI 0.1201 to 0.2691
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1937 · 95% CI 0.1190 to 0.2684
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1619 · 95% CI 0.0870 to 0.2369
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1249 · 95% CI 0.0480 to 0.2018
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1546 · 95% CI 0.0777 to 0.2315
SecondaryBronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)

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
Reported as:
Least squares mean · Percentage of predicted FVC
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
Percentage of predicted FVCIndacaterol Maleate 150 µgIndacaterol Acetate 150 µgPlacebo
5 min90.4 (86.1 to 94.6)91.2 (86.9 to 95.4)85.3 (81.1 to 89.6)
15 min90.8 (86.6 to 95.1)90.7 (86.5 to 95.0)84.9 (80.6 to 89.1)
30 min91.6 (87.4 to 95.9)91.4 (87.2 to 95.7)85.1 (80.8 to 89.3)
1 hour91.1 (86.8 to 95.3)91.1 (86.9 to 95.3)85.6 (81.4 to 89.8)
2 hours90.7 (86.4 to 94.9)91.4 (87.1 to 95.6)85.9 (81.7 to 90.2)
4 hours90.5 (86.3 to 94.8)91.3 (87.0 to 95.5)86.2 (82.0 to 90.5)
8 hours90.4 (86.1 to 94.6)90.3 (86.1 to 94.6)85.4 (81.1 to 89.6)
12 hours88.5 (84.3 to 92.8)88.2 (84.0 to 92.5)84 (79.8 to 88.3)
23 hours 15 min91.5 (87.2 to 95.7)89.9 (85.6 to 94.1)86.9 (82.6 to 91.2)
23 hours 45 min90.6 (86.4 to 94.9)90.6 (86.4 to 94.9)86.5 (82.3 to 90.8)
Statistical analysis
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 5 · 95% CI 3.1 to 7.0
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 6 · 95% CI 4 to 7.9
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 6.6 · 95% CI 4.6 to 8.5
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 5.5 · 95% CI 3.5 to 7.4
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 4.7 · 95% CI 2.8 to 6.7
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 4.3 · 95% CI 2.3 to 6.3
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 5 · 95% CI 3 to 7
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 4.5 · 95% CI 2.5 to 6.5
  • Indacaterol Maleate 150 µg · ANOVA · p = <0.001 · Mean difference (final values): 4.6 · 95% CI 2.6 to 6.7
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 4.1 · 95% CI 2.0 to 6.2
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 5.8 · 95% CI 3.9 to 7.8
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 5.8 · 95% CI 3.9 to 7.8
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 6.3 · 95% CI 4.4 to 8.3
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 5.5 · 95% CI 3.5 to 7.5
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 5.5 · 95% CI 3.5 to 7.4
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 5.0 · 95% CI 3.1 to 7.0
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 5.0 · 95% CI 3.0 to 7.0
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 4.2 · 95% CI 2.2 to 6.2
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = 0.004 · Mean difference (final values): 3.0 · 95% CI 1.0 to 5.0
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 4.1 · 95% CI 2.1 to 6.1
SecondaryBronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC

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
Reported as:
Least squares mean · Ratio
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
RatioIndacaterol MaleateIndacaterol AcetatePlacebo
5 min0.6979 (0.6728 to 0.7230)0.6952 (0.6701 to 0.7202)0.6729 (0.6478 to 0.6981)
15 min0.7002 (0.6751 to 0.7253)0.7017 (0.6766 to 0.7268)0.6672 (0.6421 to 0.6923)
30 min0.7012 (0.6761 to 0.7263)0.6996 (0.6745 to 0.7246)0.6706 (0.6455 to 0.6957)
1 hour0.7053 (0.6802 to 0.7304)0.7007 (0.6757 to 0.7258)0.6729 (0.6478 to 0.6980)
2 hour0.7085 (0.6834 to 0.7336)0.7085 (0.6834 to 0.7335)0.6747 (0.6496 to 0.6998)
4 hour0.7057 (0.6806 to 0.7308)0.7010 (0.6759 to 0.7261)0.6732 (0.6481 to 0.6984)
8 hour0.6962 (0.6710 to 0.7213)0.6967 (0.6716 to 0.7218)0.6651 (0.6399 to 0.6902)
12 hour0.6958 (0.6707 to 0.7210)0.6885 (0.6634 to 0.7135)0.6599 (0.6348 to 0.6851)
23 hour 15 min0.6898 (0.6647 to 0.7150)0.6853 (0.6602 to 0.7104)0.6572 (0.6320 to 0.6825)
23 hour 45 min0.6934 (0.6683 to 0.7186)0.6899 (0.6648 to 0.7150)0.6633 (0.6381 to 0.6886)
Statistical analysis
  • Indacaterol Maleate vs Placebo · ANOVA · p = <.001 · Mean difference (final values): 0.0249 · 95% CI 0.0139 to 0.0359
  • Indacaterol Maleate vs Placebo · ANOVA · p = <.001 · Mean difference (final values): 0.0330 · 95% CI 0.0220 to 0.0440
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0306 · 95% CI 0.0197 to 0.0416
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0324 · 95% CI 0.0214 to 0.0434
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0338 · 95% CI 0.0228 to 0.0447
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0325 · 95% CI 0.0215 to 0.0435
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0311 · 95% CI 0.0200 to 0.0422
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0359 · 95% CI 0.0248 to 0.0470
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0326 · 95% CI 0.0211 to 0.0440
  • Indacaterol Maleate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0301 · 95% CI 0.0187 to 0.0415
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0222 · 95% CI 0.0113 to 0.0332
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0344 · 95% CI 0.0234 to 0.0454
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0290 · 95% CI 0.0180 to 0.0399
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0278 · 95% CI 0.0169 to 0.0387
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0338 · 95% CI 0.0228 to 0.0447
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0278 · 95% CI 0.0168 to 0.0387
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0316 · 95% CI 0.0206 to 0.0426
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0285 · 95% CI 0.0175 to 0.0396
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0281 · 95% CI 0.0167 to 0.0394
  • Indacaterol Acetate vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.0266 · 95% CI 0.0152 to 0.0379
SecondaryBronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%

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
Reported as:
Least squares mean · Liters/second
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
Liters/secondIndacaterol Maleate 150 µgIndacaterol Acetate 150 µgPlacebo
5 min1.6968 (1.4675 to 1.9261)1.6918 (1.4628 to 1.9208)1.4962 (1.2668 to 1.7256)
15 min1.7454 (1.5160 to 1.9747)1.7458 (1.5165 to 1.9751)1.4531 (1.2238 to 1.6824)
30 min1.7347 (1.5053 to 1.9640)1.7413 (1.5122 to 1.9704)1.4690 (1.2397 to 1.6983)
1 hour1.7715 (1.5422 to 2.0008)1.7349 (1.5059 to 1.9640)1.4963 (1.2670 to 1.7256)
2 hour1.7907 (1.5613 to 2.0200)1.8074 (1.5782 to 2.0365)1.5088 (1.2795 to 1.7381)
4 hour1.7663 (1.5370 to 1.9956)1.7503 (1.5212 to 1.9795)1.4843 (1.2549 to 1.7137)
8 hour1.6755 (1.4460 to 1.9050)1.6774 (1.4483 to 1.9066)1.4217 (1.1922 to 1.6512)
12 hour1.6549 (1.4254 to 1.8844)1.5849 (1.3557 to 1.8140)1.3862 (1.1566 to 1.6158)
23 hour 15 min1.6667 (1.4370 to 1.8964)1.6257 (1.3965 to 1.8550)1.4214 (1.1910 to 1.6518)
23 hour 45 min1.6446 (1.4149 to 1.8743)1.6580 (1.4288 to 1.8873)1.4584 (1.2280 to 1.6866)
Statistical analysis
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2025 · 95% CI 0.1059 to 0.2952
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2923 · 95% CI 0.1979 to 0.3867
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2657 · 95% CI 0.1713 to 0.3601
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2752 · 95% CI 0.1808 to 0.3696
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2819 · 95% CI 0.1875 to 0.3763
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2820 · 95% CI 0.1874 to 0.3766
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2538 · 95% CI 0.1585 to 0.3492
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2687 · 95% CI 0.1732 to 0.3643
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2453 · 95% CI 0.1473 to 0.3434
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1862 · 95% CI 0.0882 to 0.2842
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1956 · 95% CI 0.1012 to 0.2899
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2927 · 95% CI 0.1979 to 0.3875
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2723 · 95% CI 0.1780 to 0.3667
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2386 · 95% CI 0.1445 to 0.3328
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2986 · 95% CI 0.2042 to 0.3930
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2661 · 95% CI 0.1715 to 0.3607
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2558 · 95% CI 0.1609 to 0.3506
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1987 · 95% CI 0.1036 to 0.2938
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.2044 · 95% CI 0.1071 to 0.3017
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 0.1997 · 95% CI 0.1023 to 0.2970
SecondaryBronchodilator Effect of Indacaterol Salts Compared to Placebo in Standardized FEV1 AUC.

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
Reported as:
Least squares mean · Liters
Bronchodilator Effect of Indacaterol Salts Compared to Placebo in Standardized FEV1 AUC.
LitersIndacaterol Maleate 150 µgIndacaterol Acetate 150 µgPlacebo
Bronchodilator Effect of Indacaterol Salts Compared to Placebo in Standardized FEV1 AUC.2.5179 ± 0.112132.5151 ± 0.112052.2703 ± 0.11213
Statistical analysis
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <.001 · Mean difference (final values): 0.2476 · 95% CI 0.1857 to 0.3095
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <.001 · Mean difference (final values): 0.2448 · 95% CI 0.1830 to 0.3066
  • Indacaterol Maleate 150 µg vs Indacaterol Acetate 150 µg · ANOVA · Mean difference (net): -0.0028 · 95% CI -0.0647 to 0.0590
SecondaryRescue Medication Usage

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
Reported as:
Least squares mean · Puffs
Rescue Medication Usage
PuffsIndacaterol Maleate 150 µgIndacaterol Acetate 150 µgPlacebo
Rescue Medication Usage1.01 ± 0.2281.01 ± 0.2271.43 ± 0.228
Statistical analysis
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = 0.009 · Mean difference (final values): -0.42 · 95% CI -0.73 to 0.11
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = 0.008 · Mean difference (final values): -0.42 · 95% CI -0.73 to 0.11
SecondaryMean Overall Peak Expiratory Flow (PEF)

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
Reported as:
Least squares mean · Liters/min
Mean Overall Peak Expiratory Flow (PEF)
Liters/minIndacaterol Maleate 150 µgIndacaterol Acetate 150 µgPlacebo
Mean Overall Peak Expiratory Flow (PEF)409.7 ± 15.06407.6 ± 15.05376.8 ± 15.06
Statistical analysis
  • Indacaterol Maleate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 33.0 · 95% CI 25.6 to 40.3
  • Indacaterol Acetate 150 µg vs Placebo · ANOVA · p = <0.001 · Mean difference (final values): 30.8 · 95% CI 23.5 to 38.2

Adverse events

Collected over until 30 days after the last Investigational Product (IP) administration. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Indacaterol Maleate 150 µg0/51 (0%)0/51 (0%)14/51 (27.5%)
Indacaterol Acetate 150 µg0/52 (0%)1/52 (1.9%)7/52 (13.5%)
Placebo0/53 (0%)0/53 (0%)9/53 (17%)
Most frequent serious events
Most frequent serious events
EventIndacaterol Maleate 150 µgIndacaterol Acetate 150 µgPlacebo
Pharyngitis streptococcalInfections and infestations0/511/520/53
SinusitisInfections and infestations0/511/520/53
Most frequent other events
Showing 10 of 21
Most frequent other events
EventIndacaterol Maleate 150 µgIndacaterol Acetate 150 µgPlacebo
CoughRespiratory, thoracic and mediastinal disorders12/510/521/53
Upper respiratory tract infectionInfections and infestations1/512/522/53
VomitingGastrointestinal disorders1/511/520/53
Blood potassium increasedInvestigations1/510/520/53
DizzinessNervous system disorders1/510/520/53
NauseaGastrointestinal disorders0/511/520/53
Alanine aminotransferase increasedInvestigations0/511/520/53
Aspartate aminotransferase increasedInvestigations0/511/520/53
Weight increasedInvestigations0/511/520/53
ArthralgiaMusculoskeletal and connective tissue disorders0/511/521/53

Baseline characteristics

Age, Continuous
Age, Continuous(years)All Participants
Mean47.7 ± 12.5
Sex: Female, Male
Sex: Female, Male(Participants)All Participants
Female36
Male18
Race (NIH/OMB)
Race (NIH/OMB)(Participants)All Participants
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American7
White47
More than one race0
Unknown or Not Reported0
07

Study locations

6 sites
  • Novartis Investigative Site
    North Dartmouth, Massachusetts 02747-3322, United States
  • Novartis Investigative Site
    Saint Louis, Missouri 63141, United States
  • Novartis Investigative Site
    Skillman, New Jersey 08558, United States
  • Novartis Investigative Site
    Raleigh, North Carolina 27607, United States
  • Novartis Investigative Site
    Medford, Oregon 97504, United States
  • Novartis Investigative Site
    El Paso, Texas 79903, United States
08

References and documents

Publications

  • Miller D, Vaidya S, Jauernig J, Ethell B, Wagner K, Radhakrishnan R, Tillmann HC. Lung function, pharmacokinetics, and tolerability of inhaled indacaterol maleate and acetate in asthma patients. Respir Res. 2020 Sep 23;21(1):248. doi: 10.1186/s12931-020-01501-1. PubMed 32967685 ↗

Study documents

  • Statistical analysis plan · Apr 16, 2018
  • Study protocol · Feb 27, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

09

Registry details

Key details

Study ID
NCT03257995
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Aug 22, 2017
Start date
Sep 5, 2017
Primary completion
Jan 17, 2018
Completion
Jan 18, 2018
Results posted
Mar 29, 2019
Last update
Jan 5, 2021

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2019. You cannot join it, but the record below documents what was studied.

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