Assess Bronchodilator Effect QVM149 Dosed Either in the Morning or Evening Compared to Placebo in Patients With Asthma

Novartis

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: Treatment C: Placebo (morning dose) and placebo (evening dose); Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose); Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03108027

CQVM149B2209

2017-000644-17 (EudraCT Number)

Details and patient eligibility

About

This was a randomized, placebo-controlled, double-blind, six-sequence, three-period cross-over study in asthma patients. The study consisted of a 14-day screening period, followed by a 14-day run-in period, and a treatment epoch which consists of three treatment periods, with a minimum duration of 14 days each followed (for the 2 first treatment periods) by a wash-out period. The duration of each treatment period may be extended up to a duration of 18 days if needed for operational reasons. The third treatment period was followed by a Study Completion evaluation at 1-7 days following the last dose. The treatment periods were separated by wash-out periods of 14 to 21 days duration.

Enrollment: 38 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patients with a documented physician diagnosis of asthma and who additionally meet the following criteria:

• Patients receiving daily treatment with an inhaled corticosteroid at a low or medium daily dose
• On a stable regimen for at least 4 weeks prior to screening.
• Pre-bronchodilator FEV1 ≥ 60 % and < 100% 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. All patients must perform a reversibility test at Screening.
• At screening, and baseline (day 1 pre-dose time) of the first treatment period, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position and again in the standing position as outlined in the SOM. Sitting and standing vital signs should be within the following ranges:
• oral body temperature between 35.0-37.5 °C
• systolic blood pressure, 90-159 mmHg
• diastolic blood pressure, 50-99 mmHg
• pulse rate, 40-90 bpm
• Hypertensive patients must have been on stable antihypertensive therapy for at least 4 weeks prior to screening to be included in the trial.
• Patients 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.

Exclusion criteria

• Contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the drugs of a similar class
• Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 1 year of Screening.
• Patients who have had previous intubation for a severe asthma ttack/exacerbation.
• Patients with a history of clinically relevant bronchoconstriction upon repeated forced expiratory maneuvers.
• History of paradoxical bronchospasm in response to inhaled medicines.
• Patients who during the run-in period prior to randomization require the use of ≥12 puffs / 24 hours of rescue medication for 48 hours (over two consecutive days) or who have a decline in PEF from the reference PEFof ≥ 30% for 6 consecutive scheduled PEF readings
• Patients who do not maintain regular day/night, waking/sleeping cycles (e.g., night shift workers).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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38 participants in 6 patient groups

Sequence 1

Experimental group

Description:

Patients will receive in a sequential order the following interventional treatments: A,B and C.

Treatment:

Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)

Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)

Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)

Sequence 2

Experimental group

Description:

Patients will receive in a sequential order the following interventional treatments: B, A and C.

Treatment:

Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)

Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)

Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)

Sequence 3

Experimental group

Description:

Patients will receive in a sequential order the following interventional treatments: C, B and A.

Treatment:

Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)

Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)

Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)

Sequence 4

Experimental group

Description:

Patients will receive in a sequential order the following interventional treatments : C, A and B.

Treatment:

Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)

Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)

Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)

Sequence 5

Experimental group

Description:

Patients will receive in a sequential order the following interventional treatments: A, C and B.

Treatment:

Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)

Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)

Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)

Sequence 6

Experimental group

Description:

Patients will receive in a sequential order the following interventional treatments: B, C and A.

Treatment:

Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)

Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)

Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)