Roflumilast Plus Montelukast in Adults With Severe Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01765192
First received: January 8, 2013
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Roflumilast
Drug: Roflumilast Placebo
Drug: Montelukast
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-blind, 4-week Cross-over Trial to Investigate The Effect of a Once-daily Combination of Roflumilast Plus Montelukast Versus 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.

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change from Baseline in pre-dose (trough) pre-bronchodilator forced expiratory volume in 1 second (FEV1) [ Time Frame: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change from Baseline in pre-dose (trough) pre-bronchodilator forced vital capacity (FVC) [ Time Frame: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84) ] [ Designated as safety issue: No ]
    FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC will be measured using spirometry in accordance with ATS/ERS consensus guidelines.

  • Change from Baseline in pre-dose (trough) pre-bronchodilator forced expiratory flow (FEF) 25-75% [ Time Frame: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84) ] [ Designated as safety issue: No ]
    FEF is a measure of how much air can be exhaled from the lungs. It is an indicator of obstruction of the smaller airways. FEF25-75% is the mid-flow rate or forced expiratory flow occurring in the middle 50% of the patient's exhaled volume, and will be measured using spirometry in accordance with ATS/ERS consensus guidelines.

  • Change from Baseline in pre-dose (trough) pre-bronchodilator peak expiratory flow (PEF) [ Time Frame: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84) ] [ Designated as safety issue: No ]
    PEF is a person's maximum speed of expiration. It measures the airflow through the bronchi and thus the degree of obstruction in the airways. PEF will be measured using spirometry in accordance with ATS/ERS consensus guidelines.

  • Change from Baseline in morning peak expiratory flow (PEF) [ Time Frame: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84) ] [ Designated as safety issue: No ]
    PEF will be measured at home using portable electronic peak flow meter. The participant will record PEF daily in the morning immediately after getting up.

  • Change from Baseline in daytime asthma symptoms [ Time Frame: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84) ] [ Designated as safety issue: No ]

    Patients will assess their daily day-time asthma symptoms according to the following scale:

    0: Very well, no symptoms.

    1. One episode of wheezing, cough or breathlessness.
    2. More than one episode of wheezing, cough or breathlessness without interfering with normal activities.
    3. Wheezing, cough or short of breath most of the day which interfered to some extent with normal activities.
    4. Asthma very bad. Unable to carry out daily activities as usual.

  • Change from Baseline in nighttime asthma symptoms [ Time Frame: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84) ] [ Designated as safety issue: No ]

    Patients will assess their daily night-time asthma symptoms according to the following scale:

    0: No symptoms, slept through the night.

    1. Slept well but some complaints in the morning.
    2. Woke up once because of asthma (inclusive early awakening).
    3. Woke up several times because of asthma (inclusive early awakening).
    4. Bad night, awake most of the night because of asthma.


Enrollment: 64
Study Start Date: February 2013
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Roflumilast/Montelukast + Montelukast
Roflumilast dose and montelukast dose, orally, then roflumilast placebo-matching dose and montelukast dose, orally.
Drug: Roflumilast
Roflumilast dose
Other Name: Daxas
Drug: Roflumilast Placebo
Roflumilast Placebo-matching dose
Other Name: placebo
Drug: Montelukast
Montelukast dose
Other Name: Singulair
Experimental: Montelukast + Roflumilast/Montelukast
Roflumilast placebo-matching dose and montelukast dose, orally, then roflumilast dose and montelukast dose, orally.
Drug: Roflumilast
Roflumilast Dose
Other Name: Daxas
Drug: Roflumilast Placebo
Roflumilast placebo-matching dose
Other Name: Placebo
Drug: Montelukast
Montelukast dose
Other Name: Singulair

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 participantor, 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01765192

Locations
Germany
Berlin, Germany
Grosshansdorf, Germany
Hamburg, Germany
Hannover, Germany
Mainz, Germany
Schwerin, Germany
Hungary
Budapest, Hungary
Nyiregyhaza, Hungary
Szarvas, Hungary
Torokbalint, Hungary
South Africa
Bloemfontein, South Africa
Cape Town, South Africa
Pretoria, South Africa
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director, MD Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01765192     History of Changes
Other Study ID Numbers: ROF-ASTHMA_202, U1111-1132-3160, 2012-002064-27, DOH-27-0213-4118
Study First Received: January 8, 2013
Last Updated: February 4, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
South Africa: National Health Research Ethics Council
Hungary: National Institute of Pharmacy

Keywords provided by Takeda:
Drug therapy

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Montelukast
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Pharmacologic Actions
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 16, 2014