Roflumilast Plus Montelukast in Adults With Severe Asthma
Information source: Takeda
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Asthma
Intervention: Roflumilast (Drug); Roflumilast placebo (Drug); Montelukast (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Takeda Official(s) and/or principal investigator(s): Medical Director, MD, Study Director, Affiliation: Takeda
Summary
The purpose of this study is to evaluate the effect of roflumilast alone and in combination
with montelukast on forced expiratory volume in 1 second (FEV1) in patients with
inadequately controlled asthma.
Clinical Details
Official title: A Phase 2, Randomized, Double-Blind, 4-week Crossover Trial to Investigate the Effect of a Once-Daily Combination of 500 µg Roflumilast Plus 10 mg Montelukast vs 10 mg Montelukast Alone on Pulmonary Function, Asthma Symptoms, and Inflammatory Markers in Subjects With Severe Asthma Not Adequately Controlled With a Combination of at Least Medium Dose Inhaled Corticosteroids and Long-Acting Beta Agonists Maintenance Therapy
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Change From Baseline in Pre-Dose (Trough) Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Secondary outcome: Change From Baseline in Pre-Dose (Trough) Pre-Bronchodilator Forced Vital Capacity (FVC)Change From Baseline in Pre-Dose (Trough) Pre-Bronchodilator Forced Expiratory Flow (FEF) 25-75% Change From Baseline in Pre-Dose (Trough) Pre-Bronchodilator Peak Expiratory Flow (PEF) Change From Baseline in Morning Peak Expiratory Flow (PEF) Change From Baseline in Daytime Asthma Symptoms Change From Baseline in Nighttime Asthma Symptoms
Detailed description:
The drug being tested in this study is called roflumilast. Roflumilast is being tested to
treat people who have asthma. This study will look at lung function and asthma symptoms of
people who take roflumilast in combination with montelukast.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. 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).
2. 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.
3. 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.
4. Is male or female and aged 18 years or above.
5. 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.
6. 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).
7. 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.
8. 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).
Exclusion Criteria:
1. 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).
2. Participation in another clinical trial during the current trial.
3. 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.
4. 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).
5. Lower respiratory tract infection not resolved 4 weeks prior to Visit 1.
6. 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.
7. Current participation in a pulmonary rehabilitation program or completion of a
pulmonary rehabilitation program within 3 months preceding Visit 1.
8. 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.
9. Has severe neuropsychiatric or neurological disorders (eg, history of depression
associated with suicidal thinking, suicidal ideation or behavior).
10. Has congestive heart failure severity grade III or IV according to the New York Heart
Association.
11. Has symptomatic ischemic heart disease (angina pectoris).
12. Has hemodynamically significant cardiac arrhythmias or heart valve deformations.
13. Has liver impairment, defined as Child-Pugh B/C and/or active viral hepatitis.
14. Has severe immunological diseases (eg, multiple sclerosis, systemic lupus
erythematosus, progressive multifocal leukoencephalopathy) or known infection with
human immunodeficiency virus (HIV).
15. Has severe acute infectious diseases (eg, tuberculosis, or acute hepatitis).
16. Has any diagnosis of a malignant disease (other than basal or squamous cell
carcinoma) within 5 years prior to Screening Visit 1.
17. Has a history of smoking within 1 year of Visit 1 and smoking history ≥10 pack years.
18. Has a history of drug abuse (defined as illicit drug use) or a history of alcohol
abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per
day) within the past 1 year prior to the Screening visit.
19. Has history of clinically significant allergies or idiosyncrasies to roflumilast,
montelukast or any inactive ingredient(s) of these products, eg, rare hereditary
problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose
malabsorption or phenylketonuria.
20. Has known highly unstable asthma defined by severe bronchoconstriction after
bronchoprovocation with isotonic saline.
21. Females of childbearing potential not willing to use acceptable contraceptive methods
such as hormonal contraceptives (oral, injection or implant) or intrauterine
contraceptive devices or who started such methods less than 2 months prior to
screening or who are not willing to use a double barrier method of contraception
(diaphragm plus condom).
22. If female, is pregnant or lactating or intending to become pregnant before, during,
or within 1 month after participating in this study; or intending to donate ova
during such time period.
23. Is required to take excluded medication.
Locations and Contacts
Berlin, Germany
Grosshansdorf, Germany
Hamburg, Germany
Hannover, Germany
Mainz, Germany
Schwerin, Germany
Budapest, Hungary
Nyiregyhaza, Hungary
Szarvas, Hungary
Torokbalint, Hungary
Bloemfontein, South Africa
Cape Town, South Africa
Pretoria, South Africa
Additional Information
Starting date: February 2013
Last updated: June 12, 2015
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