Asthma MedDRA version: 15.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Revamilast
Product Code: GRC 4039
Pharmaceutical Form: Tablet
INN or Proposed INN: Revamilast
Current Sponsor code: GRC 4039
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
Glenmark Pharmaceuticals SA
Eligibility
Sex/Gender
All
Inclusion 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 (inclusive) 3. Documented clinical diagnosis of asthma by a physician, based on GINA (2009) 4. The following patients can be included in the study, based on GINA (2009) stepwise therapy (please refer to Appendix 7 for details of alternative and preferred therapies at each step per GINA): A. Patients who are currently on preferred or alternative Step 1 or Step 2 therapy. Patients on alternative step 1 therapy can enter a placebo run in period only after appropriate washout criteria are met and after they have been switched to as needed inhaled rapid acting beta 2 agonist, upon consenting. Similarly, patients on alternative step 2 therapy can be included in the study after giving proper wash out for their therapies and switching them to low dose ICS (plus PRN salbutamol) upon consenting. B. Patients who are currently on preferred or alternative step 3 therapy, and for whom the PI, based on his clinical judgment and independent of the intent to include patients in the study, feels that such patients can be stepped down and switched to only low dose ICS (plus PRN salbutamol). Such patients can be included in the study after giving proper wash out for their therapies and switching them to low dose ICS (plus PRN Salbutamol) upon consenting. However, in case the investigator has any concern regarding stepping down patients from step 3, such patients should not be enrolled in the study. 5. FEV1 between 50% and 85% (inclusive) of the predicted value for their age, height and gender at screening and shown to be reversible (a = 12% increase in FEV1 with an absolute improvement in FEV1 of at least 200 ml) =15 minutes and upto 30 minutes after inhalation of 200 to 400 µg salbutamol via a spacer. Note: Reversibility should be determined at the time of Screening. At the investigator’s discretion, if a patient fails to meet the = 12% and 200 ml threshold, the reversibility tests may be repeated to a maximum of four measurements over one week. Once established, reversibility test need not be repeated in subsequent visits. 6. Patient judged by the investigator to be in otherwise good stable health based on medical history, physical examination, and routine laboratory data. 7. Female participants of child bearing potential must have a negative pregnancy test at screening visit. In addition, female of child bearing potential (FCBP) must agree to use TWO of the following contraceptive measures from at least 14 days prior to the first dose of study medication (i.e., 14 days prior to randomization) and continue until 28 days after dosing; combined oral contraceptive, hormonal intrauterine device, non hormonal intrauterine device, bilateral tubal ligation, barrier method of contraception (condom or occlusive cap [diaphragm/vault caps] with spermicidal foam/gel/film/cream/suppository); or vasectomized partner (sole partner). Female not of child-bearing potential (i.e. are postmenopausal or permanently sterilized [e.g. tubal occlusion, hysterectomy, bilateral salpingectomy]) will not be required to use contraception. Female subject of child bearing potential must agree to have serum pregnancy tests during all visits while on study medication and until 2 weeks after taking the last dose of study medication. 8. Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in
Exclusion criteria
Exclusion criteria: 1. Patients currently on step 4 or 5 therapy as per GINA 2009 2. Pregnant or lactating women 3. Female subjects on hormone replacement therapy 4. Suffering from relevant lung diseases (other than asthma) causing impairment in lung function (e.g. COPD [chronic bronchitis or emphysema], or obstructive sleep apnea requiring continuous positive airway pressure) 5. Past history of Alpha 1 antitrypsin deficiency 6. History or suspected hypersensitivity to PDE4 inhibitors 7. Past smoker with a history of =10 packs per year or current smoker (i.e. has smoked within the last 12 months prior to screening) 8. Recent (within 4 weeks prior to the enrolment visit) change in the patient’s usual asthma treatment. 9. Patients with risk factors for asthma exacerbation during the study, including (any of the following): a) Current requirement for > 8 puffs per day of reliever medication b) Hospitalisation for asthma i. Within 1 month preceding screening and/or ii. More than once in the 6 months preceding screening c) Treatment with systemic (oral or parenteral corticosteroid therapy within 1 month of screening or depot corticosteroid therapy within 3 months of screening) or receipt of more than 2 short courses of systemic corticosteroid therapy in the preceding year 10. Evidence of current or recent neoplastic disease (other than patients with basal or squamous cell skin cancer who are in remission /stable who are eligible to enter the study) 11. Any 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 a. Any of the following clinically significant laboratory abnormalities: • Significant renal insufficiency- Patients with serum creatinine concentration >1.5 mg/dL • Patients with a history of proteinuria >300 mg/day • Patients with a clinically significant abnormal WBC count, thrombocytopenia, or anaemia at screening • Patients with evidence of clinically relevant hepatic disease (e.g. values at screening or at randomization of more than 1.5 x ULN for aspartate aminotransferase [AST], alanine aminotransferase [ALT], bilirubin or alkaline phosphatase; history of or current bleeding oesophageal varices, ascites, encephalopathy) • Positive serology for an infectious disease (including hepatitis B or C) at screening and known case of human immunodeficiency virus [HIV] b. Patients at risk for gastrointestinal haemorrhage (e.g. chronic peptic ulceration) c. Patients with a history of clinically significant cardiovascular disease within the previous 6 months prior to screening (including, but not limited to, unstable angina, myocardial infarction, stroke, peripheral vascular disease, uncontrolled hypertension, ischemic changes on resting ECG, Congestive cardiac failure of NYHF grade III and IV ) d. Patients who have been hospitalized for any psychiatric illness in the past year, or are diagnosed with major depression 12. Baseline ECG QTc interval >450 ms or any other clinically significant ECG abnormality 13. Patients with documented or suspected or current history of alcohol or drug abuse 14. Patients who have undergone lung surgery in the previous year 15. Participation in an investigational drug trial during 30 days (or 9 half lives) p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate/ evaluate effects of revamilast on lung function in patients with chronic persistent asthma ;Secondary Objective: •To evaluate the safety and tolerability of revamilast in patients with chronic persistent asthma •To investigate the pharmacokinetics of revamilast and its metabolite GRC 4037 in patients with asthma ;Primary end point(s): The change in morning pre-dose FEV1 from baseline to day 84 ;Timepoint(s) of evaluation of this end point: Baseline to day 84 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints - - Change from baseline at days 7, 28, and 56 for morning pre-dose FEV1 - Change from baseline at days 7, 28, 56 and 84 in morning pre-dose FVC, PEF, FEF25-75% - Area under the curve of change from baseline morning pre-dose FEV1 measured at each visit to day 84 - Change from baseline in morning and evening PEF on days 7, 28, 56 and 84 (based on patient diary) - Change from baseline at days 7, 28, 56 and 84 in morning pre-dose FEV1, FVC, PEF, FEF25-75%, PEF for ICS and non ICS group - Change in asthma day time symptom score from baseline at day 84 - Change in asthma night time symptom score from baseline at day 84 - Change in number of night time awakenings from baseline at day 84 - Frequency and the use of rescue (reliever) medication (salbutamol) - Frequency and severity of asthma exacerbations - Investigator global impression of change from baseline to day 84 - Patient global impression of change from baseline to day 84 - Plasma pharmacokinetics of revamilast and its metabolite GRC 4037 - Change in blood cell counts from baseline to day 84 o Eosinophils cell count o Differential cell count including neutrophils, lymphocytes, monocytes, basophiles o Total leukocyte count;Timepoint(s) of evaluation of this end point: As specified in E.5.2 | — |
Countries
Czech Republic, India, Poland, Russian Federation, United Kingdom
Contacts
Public ContactBallari Brahmachari
Glenmark Pharmaceuticals SA
Outcome results
None listed