Clinical trial NCT03257995: Pharmacodynamics, Safety, Tolerability, and Pharmacokinetics of Two Orally Inhaled Indacaterol Salts in Adult Subjects With Asthma.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: asthma, asthma attack, difficulty breathing, bronchial diseases, lung, lung diseases, inhaled drugs, bronchodilator, inhaled corticosteriod
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-08-22
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.).

Primary outcomes:
measure: Trough FEV1
timeFrame: Day 14 of each of the three treatment periods
Secondary outcomes:
measure: Pharmacokinetics AUC 0-24hours at Steady State
timeFrame: Day 14 of each of the three treatment periods
measure: The Maximum Concentration (Cmax) at Steady State (ss)
timeFrame: Day 14 of each of the three treatment periods
measure: Time of Maximal Plasma Concentration (Tmax) at Steady State
timeFrame: Day 14 of each of the three treatment periods
measure: The Lowest Plasma (or Serum or Blood) Concentration (Cmin) at Steady State
timeFrame: Day 14 of each of the three treatment periods
measure: Relative Bioavailability (Frel) of Indacaterol Acetate and Indacaterol Maleate
timeFrame: Day 14
measure: Time to Peak FEV1 on Day 14
timeFrame: Day 14 of each of the three treatment periods
measure: Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
timeFrame: Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min
measure: Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
timeFrame: Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min
measure: Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
timeFrame: 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
measure: Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
timeFrame: Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min
measure: Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
timeFrame: Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min
measure: Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
timeFrame: Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45min
measure: Bronchodilator Effect of Indacaterol Salts Compared to Placebo in Standardized FEV1 AUC.
timeFrame: Pre-dose to 4 hours post-dose on Day 14 of each of the three treatment periods
measure: Rescue Medication Usage
timeFrame: 14 days of treatment for each of the three treatment periods
measure: Mean Overall Peak Expiratory Flow (PEF)
timeFrame: Days 8 through Day 14 of each of the three treatment periods
Other outcomes:
Locations:
city: North Dartmouth
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Skillman
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Raleigh
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Medford
country: United States
facility: Novartis Investigative Site
state: Oregon
city: El Paso
country: United States
facility: Novartis Investigative Site
state: Texas
Study officials:
References:
citation: 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.