Unexplained or Refractory Chronic Cough MedDRA version: 21.1 Level: LLT Classification code 10066656 Term: Chronic cough System Organ Class: 100000004855
Conditions
Interventions
Product Code: BLU-5937
Pharmaceutical Form: Tablet
INN or Proposed INN: Methyl (S)-2-((2-(2,6-difluoro-4-(methylcarbamoyl)phenyl)-7-methylimidazo[1,2-a]pyridin-3-yl)methyl)morpholine-4-carboxylate
Cur
Sponsors
Bellus Health Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have provided written consent and are willing and able to comply with all aspects of the protocol 2. Women and Men between 18 and 80 years of age inclusive 3. Chest radiograph or CT thorax within the last 12 months not demonstrating any abnormality considered to be significantly contributing to the chronic cough in the opinion of the Principal Investigator and Medical Monitor 4. Have unexplained or refractory chronic cough for at least one year: a cough that is unresponsive to at least 8 weeks of targeted treatment for identified underlying triggers including reflux disease, asthma and post-nasal drip or unexplained cough; or a cough for which no objective evidence of an underlying trigger can be determined after investigation (see Appendix 1) 5. Cough Count of = 10 per hour (Cough Count at Screening) 6. A score of = 40mm on the Cough Severity VAS at Screening 7. Women of child-bearing potential must have a negative serum pregnancy test at Screening. 8. Women of child-bearing potential must use a highly effective contraception method from Screening through to the Follow-Up Visit. Acceptable birth control methods include: a. Intrauterine device (IUD) or intrauterine system (IUS); b. Tubal ligation; or male sterilization. c. When in line with the preferred life style of the subject, true and complete abstinence (not periodic abstinence) is acceptable. For the purposes of this study, a female of childbearing potential is defined as any female who has experienced menarche and is pre-menopausal; a postmenopausal state is defined as no menses for 12 months without an alternative medical cause in a previously menstruating female. Note: In this study, oral, injected or implanted contraceptives are not considered an acceptable birth control method due to the fact that BLU-5937 showed potential induction of CYP3A4 in vitro and no DDI studies have been conducted with these contraceptives yet. 9. Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control (one method as listed in Inclusion Criteria 8), 1 of which must be a barrier method, and make no donation of sperm from Screening until 3 months after the last dose of study drug Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 26 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1. Current Smoker 2. Individuals who have given up smoking within the past 6 months, or those with >20 pack-year smoking history 3. Diagnosis of COPD, bronchiectasis, idiopathic pulmonary fibrosis based on clinician assessment 4. Treatment with an ACE-inhibitor as the potential cause of a subject’s cough, or requiring treatment with an ACE-inhibitor during the study or within 4 weeks prior to the Baseline/Visit 2 (Day 0) 5. FEV1/FVC 160 mm Hg or a diastolic blood pressure (DBP) >100 mm Hg 14. Clinically significant abnormal electrocardiogram (ECG) at Screening, including any of the following: a. QTcF interval > 450 milliseconds b. Atrial fibrillation or atrial flutter c. Heart rate 110 bpm d. Second degree or third degree (complete) AV block e. Left bundle branch block (including hemiblock) f. Wolf-Parkinson-White Syndrome g. Personal or family history of congenital long QT syndrome or family history of sudden death 15. Clinically significant abnormal laboratory tests at Screening, including: a. Alkaline phosphatase (ALP), alanine aminotransferase (ALT, SGPT), aspartate aminotransferase (AST, SGOT), >150% of the upper limit of normal (ULN), gamma-glutamyl transferase (GGT) >200% of the upper limit of normal (ULN) or Total bilirubin above the upper limit of normal (ULN) b. Creatinine >200% of the upper limit of normal (ULN) c. Haemoglobin 3 × ULN 18. Breastfeeding 19. Treatment with an investigational drug or biologic within 60 days preceding the first dose of study medication or plans to take another investigational drug or biologic within 30 days of study completion 20. Blood donation within 56 days or plasma donation within 7 days prior to dosing 21. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator or Sponsor, would make the subject inappropriate for entry into this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the efficacy and safety of BLU-5937 for the treatment unexplained, refractory chronic cough.;Secondary Objective: The secondary objective is to establish the optimal therapeutic doses for the Phase 2b/3 studies.;Primary end point(s): Change from baseline in awake cough frequency (cough recorder) at end of each dose level.;Timepoint(s) of evaluation of this end point: At end of each dose level | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline in 24-hour cough frequency (cough recorder) at end of each dose level and follow up • Change from baseline in awake cough frequency (cough recorder) at follow up • Change from baseline in cough severity as measured with VAS at end of each dose level and follow up • Change from baseline in Leicester cough questionnaire total score at end of each treatment period • Global Rating of Change scale at end of each dose level and follow up;Timepoint(s) of evaluation of this end point: • Change from baseline in 24-hour cough frequency (cough recorder) at end of each dose level and follow up • Change from baseline in awake cough frequency (cough recorder) at follow up • Change from baseline in cough severity as measured with VAS at end of each dose level and follow up • Change from baseline in Leicester cough questionnaire total score at end of each treatment period • Global Rating of Change scale at end of each dose level and follow up | — |
Countries
United Kingdom, United States
Contacts
Public ContactSenior VP Drug Development
Bellus Health Inc.
Outcome results
None listed