A Study Of The Efficacy, Safety, And Tolerability of BLU-5937 for the Treatment of Chronic Cough with no Apparent Cause

Phase 1

• Conditions: nexplained or Refractory Chronic Cough; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]; MedDRA version: 21.1Level: LLTClassification code 10066656Term: Chronic coughSystem Organ Class: 100000004855

• Registration Number: EUCTR2019-000375-16-GB
• Lead Sponsor: Bellus Health Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-03-13
• Last Update Posted: 25 May 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 51

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

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 < 60%
6. History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline/Visit 2 (Day 0)
7. History of opioid use within 1 week of the Baseline/Visit 2 (Day 0)
8. Requiring concomitant therapy with prohibited medications (see Section 4.4)
9. Medical history of hypogeusia/dysgeusia or known presence of a dysfunction in his/her ability to taste
10. History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects with <3 excised basal cell carcinomas)
11. History of a diagnosis of drug or alcohol dependency or abuse within the last 3 years
12. Any condition possibly affecting drug absorption (e.g., gastrectomy, gastroplasty, any type of bariatric surgery, vagotomy, or bowel resection)
13. Screening systolic blood pressure (SBP) >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 <40 beats per minute >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 < 10 gm/dL, WBC count <2500 mm3, neutrophil count <1500 mm3, platelet count <100 × 103/mm3
d. Positive tests for drugs of abuse (certain drugs of abuse are acceptable for non-cough indications see section 4.4)
16. Significant coagulopathy as defined by a known hereditary deficiency of coagulation factors or platelet function or an unexplained elevation of the prothrombin time (PT) or international normalized ratio (INR) of =1.5
17. Unexplained creatine kinase concentration >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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified