Clinical trial NCT01436890: A Clinical Trial to Study the Effects of Revamilast in Patients With Chronic Persistent Asthma
Official title: A Phase II, 12-week Randomized, Double-blind, Triple Dummy, Parallel Group, Placebo-controlled, Dose Range Finding Study to Evaluate Safety, Tolerability and Efficacy of Revamilast in Patients With Chronic Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Chronic Persistent Asthma
Lead sponsor: Glenmark Pharmaceuticals Ltd. India
Sponsor class: INDUSTRY
Collaborators: name: Glenmark Pharmaceuticals S.A.
First posted: 2011-09-20
Enrollment: 273
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Asthma is a common, chronic inflammatory disease of the bronchial airways, with a reported prevalence in most industrialized countries of between 5 to 10 % of the adult population. Asthma is clinically characterized by repeated episodes of wheezing, breathlessness, chest tightness, and coughing; usually in the presence of variable airflow obstruction that is often reversible either spontaneously or with treatment (The Global Initiative for Asthma (GINA), 2009).

Drug treatment of asthma has focused on anti-inflammatory therapy in all but the mildest, intermittent cases. Inhaled corticosteroids have been shown to be anti-inflammatory in asthma, but chronic use of these agents may be associated with a range of side effects, especially at high doses. In asthma, there remains a need for the development of novel anti-inflammatory therapies that are at least equally effective and possess a superior safety profile in comparison to corticosteroids.

This is a randomized, double-blind, triple dummy, placebo controlled, parallel group, dose ranging study. The study will be conducted in adult patients with a diagnosis of chronic persistent asthma with an Forced Expiratory Volume in one second(FEV1) of 50% to 80% of the predicted value. Study will enroll 448 patients globally (278 from India) across different centers.

Patients will be recruited after providing written informed consent. After screening and run in period, patient will be randomized (patient meeting randomization criteria) in 1:1:1:1 ratio to receive either one of the three dose regimens of revamilast or placebo.

The primary objective of the study is to evaluate the effect of revamilast on lung function as assessed by Forced Expiratory Volume in one second (FEV1) after the therapy (12 weeks). Secondary objective includes area under curve for FEV1, Change in asthma symptoms, patient / investigator's global assessments and safety. Patients will be followed for safety and efficacy assessment at week 1, 4, 8 12 and 14 after start of therapy.


Eligibility criteria: Inclusion Criteria:

1. The patient provides written informed consent to participate in the study
2. Male or female patient aged 18 to 65 years
3. Documented diagnosis of asthma
4. Forced Expiratory Volume in One Second (FEV1) between 50% and 80% of the predicted value
5. Patient judged by the investigator to be in otherwise good stable health based on medical history, physical examination, and routine laboratory data
6. Female participants must have a negative pregnancy test at screening visit
7. Males must agree to use barrier contraception while on study medication and for 90 days after taking the last dose of study medication

Exclusion Criteria:

1. Pregnant or lactating women
2. Female subjects on hormone replacement therapy or hormonal contraceptives
3. Suffering from relevant lung diseases (other than asthma) causing impairment in lung function
4. Past smoker with a history of ≥10 pack per year or current smoker
5. Recent change in the patient's usual asthma treatment
6. Patients with risk factors for asthma exacerbation during the study, including (any of the following):

   * Current requirement for \> 8 puffs per day of reliever medication.
   * Hospitalization for asthma
   * Treatment with systemic corticosteroid therapy within 3 months
7. Evidence of current or recent neoplastic disease
8. Clinically significant cardiovascular, haematological, endocrine, neurological, gastrointestinal, psychiatric, metabolic, immunologic, infectious, hepatic, renal, gynaecological disease or other condition that the investigator considers detrimental to the patient's participation in the study or that may prevent the successful completion of the study
9. Positive serology for an infectious disease (including hepatitis B or C) at screening and known case of human immunodeficiency virus \[HIV\]
10. Patients who have been hospitalized for any psychiatric illness in the past year, or are diagnosed with major depression
11. Clinically significant ECG Abnormality at baseline
12. Patients with documented or suspected or current history of alcohol and drug abuse
13. Patients who have undergone lung surgery in the previous year
14. Participation in an investigational drug trial during 30 days preceding screening

Primary outcomes:
measure: Change in Forced Expiratory Volume in One Second (FEV1) from baseline to week 12
timeFrame: Baseline to 12 weeks
Secondary outcomes:
measure: Change in morning pre-dose Forced Vital Capacity (FVC) from baseline to week 12
timeFrame: baseline to 12 weeks
measure: Area under the curve of Forced Expiratory Volume in One Second (FEV1)
timeFrame: 12 weeks
measure: Change in asthma day time symptom score from baseline to week 12
timeFrame: Baseline to 12 weeks
measure: Frequency and severity of asthma exacerbations during treatment period
timeFrame: 12 weeks
measure: Change in investigator global impression from baseline to week 12
timeFrame: Baseline to 12 weeks
measure: Change in patient global impression from baseline to week 12
timeFrame: Baseline to 12 weeks
measure: Change in morning pre-dose Peak Expiratory Flow (PEF) from baseline to week 12
timeFrame: Baseline to 12 weeks
measure: Change in morning pre-dose PEF25-75% (Forced expiratory flow 25-75%) from baseline to week 12
timeFrame: Baseline to 12 weeks
Other outcomes:
Locations:
city: Brno
country: Czech Republic
facility: HORNMED s.r.o.
city: Jindřichův Hradec
country: Czech Republic
facility: Sdružená pneumologická a anesteziologická ambulance
city: Neratovice
country: Czech Republic
facility: Private pulmonatory ambulance
city: Hyderabad
country: India
facility: Kunal Institute of Medical Specialities Pvt. Ltd
state: Andhra Pradesh
city: Nellore
country: India
facility: Narayana Medical College & Hospital
state: Andhra Pradesh
city: Secunderabad
country: India
facility: Yashoda Hospital
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Vasavi Hospital and Research Centre
state: Andra Pradesh
city: Hyderabad
country: India
facility: Saboo hospital and research centre
state: Andra Pradesh
city: Ponda
country: India
facility: Rutuja Allergy , Chest and General Clinic
state: Goa
city: Ahmedabad
country: India
facility: Gujarat Pulmonary & Critical Care Clinic
state: Gujarat
city: Bangalore
country: India
facility: Chest and Maternity Centre
state: Karnataka
city: Bangalore
country: India
facility: M S Ramaiah Medical College & Teaching Hospital
state: Karnataka
city: Bangalore
country: India
facility: Narayanan Hrudayalaya Hospital
state: Karnataka
city: Mangalore
country: India
facility: Kasturba Medical College Hospital
state: Karnataka
city: Thrissur
country: India
facility: Westfort Hi-tech Hospital Ltd
state: Kerala
city: Indore
country: India
facility: Indore Chest Centre
state: Madhya Pradesh
city: Mumbai
country: India
facility: Prince Aly Khan Hospital
state: Maharashtra
city: Mumbai
country: India
facility: The Bhatia Hospital
state: Maharashtra
city: Nagpur
country: India
facility: KRIMS Hospitals
state: Maharashtra
city: Nagpur
country: India
facility: Getwell Hospital & Research Institute
state: Maharashtra
city: Pune
country: India
facility: Chest Research Foundation
state: Maharashtra
city: Jaipur
country: India
facility: Shwaas Center, Navkar Hospital
state: Rajastan
city: Jaipur
country: India
facility: Asthma Bhawan
state: Rajasthan
city: Jaipur
country: India
facility: Dr Khippal's Clinic
state: Rajasthan
city: Chennai
country: India
facility: Chennai Thoracic Research Institute
state: Tamil Nadu
city: Vellore
country: India
facility: Christian Medical College
state: Tamil Nadu
city: Kolkata
country: India
facility: National Allergy Asthma Bronchitis Institute
state: West Bengal
city: Goa
country: India
facility: T B and Chest Disease Hospital
city: New Delhi
country: India
facility: MAMC & Associated Lok Nayak Hospitals
city: Bialystok
country: Poland
facility: NZOZ 'Promedica'
city: Gdansk
country: Poland
facility: Nzoz Clinica Vitae
city: Krakow
country: Poland
facility: Landa Specjalistyczne Gabinety Lekarskie
city: Krakow
country: Poland
facility: Prywatna Praktyka Lekarska
city: Lodz
country: Poland
facility: Prywatny Gabinet Specjalistyczny
city: Lubin
country: Poland
facility: Cdt Medicus
city: Poznan
country: Poland
facility: Centrum Alergologii Teresa Hofman
city: Strzelce Opolskie
country: Poland
facility: Centrum Medyczne Lucyna Andrzej Dymek
city: Elektrostal
country: Russian Federation
facility: State Healthcare Institution
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital of Russian Academy of Science
city: Moscow
country: Russian Federation
facility: State Healthcare Institution of Moscow
city: Saratov
country: Russian Federation
facility: State Educational Healthcare Institution
city: London
country: United Kingdom
facility: London Chest Hospital Department of Respiratory Medicine
state: UK
Study officials:
affiliation: Glenmark Pharmaceuticals Ltd
name: Dr Ballari Brahmachari
role: STUDY_DIRECTOR
References: