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

Novartis

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: Placebo; Drug: Indacaterol maleate; Drug: Indacaterol acetate

Study type: Interventional

Funder types: Industry

Identifiers

NCT03257995

CQVM149B2203

Details and patient eligibility

About

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

Full 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.

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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54 participants in 6 patient groups

Sequence 1

Experimental group

Description:

A-B-C

Treatment:

Drug: Indacaterol acetate

Drug: Indacaterol maleate

Drug: Placebo

Sequence 2

Experimental group

Description:

B-C-A

Treatment:

Drug: Indacaterol acetate

Drug: Indacaterol maleate

Drug: Placebo

Sequence 3

Experimental group

Description:

C-A-B

Treatment:

Drug: Indacaterol acetate

Drug: Indacaterol maleate

Drug: Placebo

Sequence 4

Experimental group

Description:

A-C-B

Treatment:

Drug: Indacaterol acetate

Drug: Indacaterol maleate

Drug: Placebo

Sequence 5

Experimental group

Description:

B-A-C

Treatment:

Drug: Indacaterol acetate

Drug: Indacaterol maleate

Drug: Placebo

Sequence 6

Experimental group

Description:

C-B-A

Treatment:

Drug: Indacaterol acetate

Drug: Indacaterol maleate

Drug: Placebo