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

NCT03108027 | Completed Phase 2 Results

• 2 other identifiers: CQVM149B22092017-000644-17
• Study Type: interventional
• Target: 38
• Locations: 3 countries
• Sites: 7

Brief Summary

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.

Conditions

Asthma

Keywords

QVM149,; asthma,; allergic asthma,; allergy triggered asthma,; reactive asthma,; asthma attack,; difficulty breathing

Outcome Measures

Primary Outcomes (1)

• FEV1 Standardized Area Under the Curve (AUC 0-24h) After Last Evening Dose of 14-day Treatment Period

  Weighted mean forced expiratory volume in 1 second (FEV1) over 24 h (AUC0-24h) following 14 days of treatment with QVM149 dosed in the morning, QVM149 dosed in the evening and placebo.

  At the end of each treatment period day 14 pre-dose to 24 hours post-dose.

Secondary Outcomes (2)

• Trough FEV1 After 24h

  At the end of each treatment period day 14 pre-dose to 24 hours post-dose.

• Peak Expiratory Flow (PEF)

  From treatment period start through study completion (up to 19 weeks).

Study Arms (6)

Sequence 1

EXPERIMENTAL

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

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

Sequence 2

EXPERIMENTAL

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

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

Sequence 3

EXPERIMENTAL

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

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

Sequence 4

EXPERIMENTAL

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

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

Sequence 5

EXPERIMENTAL

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

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

Sequence 6

EXPERIMENTAL

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

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

Interventions

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

Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

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

QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

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

Placebo (morning dose) and placebo (evening dose)

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Frankfurt Am Main Hessen, 60596, Germany

Location

Novartis Investigative Site

Großhansdorf, 22947, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Wiesbaden, 65187, Germany

Location

Novartis Investigative Site

Groningen, GZ, 9713, Netherlands

Location

Novartis Investigative Site

Machester, M23 9QZ, United Kingdom

Location

Related Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

MeSH Terms

Conditions

Asthma; Dyspnea

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceutical

novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind masking.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is to assess the bronchodilator effects of QVM149 dosed once daily either in the morning or in the evening for 2 weeks compared to placebo. It will provide evidence of the comparability of lung function effects of QVM149 irrespective of the administration schedule

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: April 11, 2017
• Study Start: June 26, 2017
• Primary Completion: February 24, 2018
• Study Completion: February 24, 2018
• Last Updated: January 5, 2021
• Results First Posted: May 21, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5); NL (1); GB (1)