NCT03257995CompletedPhase 2
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
Novartis Pharmaceuticals1 site in 1 country54 target enrollmentStarted: September 5, 2017Last updated:
Conditions
Interventions
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 54
- Locations
- 1
- Primary Endpoint
- Trough FEV1
Study Overview
Brief Summary
This study is a randomized, double-blind, placebo-controlled, three-period cross-over study in approximately 54 subjects with asthma.
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
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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/m
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.).
Arms & Interventions
Sequence 2
Experimental
B-C-A
Intervention: Placebo (Drug)
Sequence 1
Experimental
A-B-C
Intervention: Indacaterol maleate (Drug)
Sequence 1
Experimental
A-B-C
Intervention: Indacaterol acetate (Drug)
Sequence 1
Experimental
A-B-C
Intervention: Placebo (Drug)
Sequence 2
Experimental
B-C-A
Intervention: Indacaterol maleate (Drug)
Sequence 2
Experimental
B-C-A
Intervention: Indacaterol acetate (Drug)
Sequence 3
Experimental
C-A-B
Intervention: Indacaterol maleate (Drug)
Sequence 3
Experimental
C-A-B
Intervention: Indacaterol acetate (Drug)
Sequence 3
Experimental
C-A-B
Intervention: Placebo (Drug)
Sequence 4
Experimental
A-C-B
Intervention: Indacaterol maleate (Drug)
Sequence 4
Experimental
A-C-B
Intervention: Indacaterol acetate (Drug)
Sequence 4
Experimental
A-C-B
Intervention: Placebo (Drug)
Sequence 5
Experimental
B-A-C
Intervention: Indacaterol maleate (Drug)
Sequence 5
Experimental
B-A-C
Intervention: Indacaterol acetate (Drug)
Sequence 5
Experimental
B-A-C
Intervention: Placebo (Drug)
Sequence 6
Experimental
C-B-A
Intervention: Indacaterol maleate (Drug)
Sequence 6
Experimental
C-B-A
Intervention: Indacaterol acetate (Drug)
Sequence 6
Experimental
C-B-A
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Trough FEV1
Time Frame: 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 Outcomes
- Pharmacokinetics AUC 0-24hours at Steady State(Day 14 of each of the three treatment periods)
- The Maximum Concentration (Cmax) at Steady State (ss)(Day 14 of each of the three treatment periods)
- Relative Bioavailability (Frel) of Indacaterol Acetate and Indacaterol Maleate(Day 14)
- 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 Lowest Plasma (or Serum or Blood) Concentration (Cmin) at Steady State(Day 14 of each of the three treatment periods)
- 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)
- Time of Maximal Plasma Concentration (Tmax) at Steady State(Day 14 of each of the three treatment periods)
- 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)
- 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)
- Time to Peak FEV1 on Day 14(Day 14 of each of the three treatment periods)
- 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)
- Rescue Medication Usage(14 days of treatment for each of the three treatment periods)
- Mean Overall Peak Expiratory Flow (PEF)(Days 8 through Day 14 of each of the three treatment periods)
- 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 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)
Investigators
Study Sites (1)
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