Roflumilast Plus Montelukast in Adults With Severe Asthma

NCT01765192 | Completed Phase 2 Results

• 4 other identifiers: ROF-ASTHMA_202U1111-1132-31602012-002064-27DOH-27-0213-4118
• Study Type: interventional
• Target: 64
• Locations: 3 countries
• Sites: 13

Brief Summary

This study will evaluate the effect of roflumilast 500 μg once daily (QD) plus montelukast 10 mg QD versus 10 mg montelukast QD alone on predose (trough) prebronchodilator forced expiratory volume in the first second (FEV1).

Conditions

Asthma

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Pre-Dose (Trough) Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)

  FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 will be measured using spirometry in accordance with the American Thoracic Society / European Respiratory Society (ATS/ERS) consensus guidelines. An ANCOVA model with treatment sequence, treatment period, and study treatment as fixed factors with Baseline FEV1 measurement as the covariate was used for analysis.

  Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)

Secondary Outcomes (6)

• Change From Baseline in Pre-Dose (Trough) Pre-Bronchodilator Forced Vital Capacity (FVC)

  Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)

• Change From Baseline in Pre-Dose (Trough) Pre-Bronchodilator Forced Expiratory Flow (FEF) 25-75%

  Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)

• Change From Baseline in Pre-Dose (Trough) Pre-Bronchodilator Peak Expiratory Flow (PEF)

  Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)

• Change From Baseline in Morning Peak Expiratory Flow (PEF)

  Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)

• Change From Baseline in Daytime Asthma Symptoms

  Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)

Study Arms (2)

Roflumilast plus montelukast, then placebo plus montelukast

EXPERIMENTAL

Participants in sequence 1 received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks followed by a 4-week washout period and then received placebo plus montelukast 10 mg orally once daily for 4 weeks.

Drug: Roflumilast; Drug: Roflumilast placebo; Drug: Montelukast

Placebo plus montelukast, then roflumilast plus montelukast

EXPERIMENTAL

Participants in sequence 2 received placebo plus montelukast 10 mg orally once daily for 4 weeks followed by a 4-week washout period and then received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks.

Drug: Roflumilast; Drug: Roflumilast placebo; Drug: Montelukast

Interventions

Roflumilast DRUG

Roflumilast was supplied in tablets.

Also known as: Daxas, Daliresp

Placebo plus montelukast, then roflumilast plus montelukast; Roflumilast plus montelukast, then placebo plus montelukast

Roflumilast placebo DRUG

Roflumilast placebo was supplied in tablets.

Placebo plus montelukast, then roflumilast plus montelukast; Roflumilast plus montelukast, then placebo plus montelukast

Montelukast DRUG

Montelukast was supplied in tablets.

Also known as: Singulair, Pluralair

Placebo plus montelukast, then roflumilast plus montelukast; Roflumilast plus montelukast, then placebo plus montelukast

Eligibility Criteria

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

You may qualify if:

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements (ie, to follow clinical trial procedures and Investigator instructions adequately).
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Has a documented physician diagnosis of severe asthma consistent with global initiative for asthma (GINA) step 4 clinical features \[Gina 2011\] for at least 6 months.
• Is male or female and aged 18 years or above.
• Has been treated with a fixed or free combination of at least medium-dose inhaled corticosteroid (ICS) (ie, ≥ 250 µg fluticasone propionate daily or equivalent ICS) plus long-acting beta agonist (LABA) for at least 3 months prior to Screening with stable ICS dose for at least 4 weeks before Visit 2.
• Shows GINA-defined uncontrolled asthma or an asthma control questionnaire (ACQ-7) score ≥1.5 despite at least medium dose ICS/LABA therapy within 4 weeks prior to Visit 1 (Screening).
• Shows a pre-bronchodilator FEV1 of \> 55% and ≤ 85% of predicted at Visit 1 (Screening). For participants performing induced sputum FEV1 must be in addition \> 1 liter.
• Has airway obstruction proven to be reversible by an improvement of FEV1 of at least 12% and 200 mL after inhalation of a short-acting bronchodilator. This can be either documented in the medical history (with supporting spirometry recordings) in the previous 12 months or demonstrated during screening at Visit 1 (Screening).

You may not qualify if:

• Has received any investigational compound within 30 days prior to the start of the clinical trial or has participated in the active treatment phase of another clinical trial where a persisting pharmacodynamic effect of the trial treatment of that clinical trial cannot be excluded (eg, participant is well into a treatment free follow-up phase).
• Participation in another clinical trial during the current trial.
• Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
• Severe asthma exacerbation not resolved 4 weeks prior to Visit 1, (defined by the need for oral or parenteral glucocorticosteroid intake for at least 3 days and/or hospitalization or emergency room visit with the need for oral or parenteral corticosteroid use).
• Lower respiratory tract infection not resolved 4 weeks prior to Visit 1.
• A diagnosis of chronic obstructive pulmonary disease (COPD) (based on Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] criteria) and/or other relevant forms of lung disease (eg, history of primary bronchiectasis, cystic fibrosis, idiopathic (pan)bronchiolitis or bronchiolitis obliterans, bronchopulmonary allergic aspergillosis, Churg-Strauss Syndrome, paradoxical vocal cord closure, lung resection, lung cancer, interstitial lung disease \[eg, fibrosis, silicosis, sarcoidosis\], or active tuberculosis) that may interfere with the evaluation of a treatment response.
• Current participation in a pulmonary rehabilitation program or completion of a pulmonary rehabilitation program within 3 months preceding Visit 1.
• Has, in the judgment of the investigator, clinically significant abnormal laboratory values (hematology or biochemistry) at screening suggesting an undiagnosed disease requiring further clinical evaluation.
• Has severe neuropsychiatric or neurological disorders (eg, history of depression associated with suicidal thinking, suicidal ideation or behavior).
• Has congestive heart failure severity grade III or IV according to the New York Heart Association.
• Has symptomatic ischemic heart disease (angina pectoris).
• Has hemodynamically significant cardiac arrhythmias or heart valve deformations.
• Has liver impairment, defined as Child-Pugh B/C and/or active viral hepatitis.
• Has severe immunological diseases (eg, multiple sclerosis, systemic lupus erythematosus, progressive multifocal leukoencephalopathy) or known infection with human immunodeficiency virus (HIV).
• Has severe acute infectious diseases (eg, tuberculosis, or acute hepatitis).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (13)

Unknown Facility

Berlin, Germany

Location

Unknown Facility

Großhansdorf, Germany

Location

Unknown Facility

Hamburg, Germany

Location

Unknown Facility

Hanover, Germany

Location

Unknown Facility

Mainz, Germany

Location

Unknown Facility

Schwerin, Germany

Location

Unknown Facility

Budapest, Hungary

Location

Unknown Facility

Nyíregyháza, Hungary

Location

Unknown Facility

Szarvas, Hungary

Location

Unknown Facility

Törökbálint, Hungary

Location

Unknown Facility

Bloemfontein, South Africa

Location

Unknown Facility

Cape Town, South Africa

Location

Unknown Facility

Pretoria, South Africa

Location

MeSH Terms

Conditions

Asthma

Interventions

Roflumilast; montelukast

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: AstraZeneca Clinical Study Information Center
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• AstraZeneca AstraZeneca

  AstraZeneca

  STUDY DIRECTOR

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
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2013
• First Posted: January 10, 2013
• Study Start: February 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: February 1, 2017
• Results First Posted: July 8, 2015

Record last verified: 2016-09

Locations

HU (4); DE (6); ZA (3)