Subjects with Chronic Cough MedDRA version: 17.1 Level: LLT Classification code 10066656 Term: Chronic cough System Organ Class: 100000004855
Conditions
Interventions
Product Name: AF-219
Product Code: AF-219
Pharmaceutical Form: Tablet
Current Sponsor code: AF-219
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutic
Sponsors
Afferent Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects are eligible for inclusion if they meet the following inclusion criteria: 1. Men and women =18 and =80 years of age 2. Written informed consent from the subject 3. History of cough for more than 8 weeks 4. Normal chest radiograph 5. Idiopathic or treatment resistant cough (idiopathic defined as a cough for which no objective evidence of an underlying trigger can be determined after investigation) or a cough that is unresponsive to 8 weeks of targeted treatment for identified underlying triggers including reflux disease, asthma and post-nasal drip (treatment-resistant).* 6. Women must be post-menopausal, with no menses for 12 months without an alternative medical cause, or if of child-bearing potential must have a negative pregnancy test and agree to use one of the following acceptable birth control methods from screening visit to follow-up contact: • True complete abstinence when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence such as calendar, ovulation, symptothermal or post-ovulation methods are not acceptable methods of contraception), or • Surgical sterilization of either the female subject in study (e.g., bilateral tubal ligation) or of her male partner (vasectomy with documented azoospermia) if he is the sole partner of that subject, or • Established hormonal contraception (implantable, patch, oral or intramuscular [IM]) administered for at least one month prior to study medication administration • An intrauterine device (IUD) or intrauterine system (IUS) with failure rate of less than 1% per year inserted by qualified physician at least one month prior to study medication administration, or • Double barrier method: condom and occlusive cap (diaphragm) with spermicidal foam/gel/film/cream/suppository, * Investigations will include bronchial provocation testing (to exclude asthma), ear, nose, and throat (ENT) examination (to exclude post-nasal drip syndrome) and either 24 hour impedance/pH testing or an 8 week trial of twice daily proton pump inhibitor/H2 receptor blocker (to exclude reflux disease). All these tests are performed routinely according to North West Lung Centre management protocol in the clinic and only subjects who have already been investigated will be invited to participate in the study Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: Subjects must NOT meet any of the following 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. 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 Day 0. 4. FEV1/FVC 35 9. History of urinary tract infection within 6 months prior to Screening 10. History or symptoms of renal disease, including nephro/urolithiasis, pyelonephritis, or renal obstructive disease 11. History of conditions or disorders which predispose to nephrolithiasis such as frequent and recurrent urinary tract infections, Type 1 renal tubular acidosis, cystinuria, gout, hyperparathyroidism, inflammatory bowel disease, short bowel syndrome, bariatric surgery 12. History of stroke or transient ischemic attack within 2 years prior to Screening or residual deficits that would preclude completion of study activities 13. History of life-threatening neoplasms within 5 years prior to study entry, other than carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin 14. History of drug or alcohol dependency or abuse within approximately the last 5 years 15. Clinically significant depression or a history of suicide behavior or suicidal ideation unless the Investigator and Medical Monitor conclude, based upon an assessment by a qualified mental health professional, that the subject may safely participate in the study 16. In the opinion of the Investigator and Medical Monitor, an uncontrolled or unstable, clinically significant neurological, psychiatric, respiratory, cardiovascular, peripheral vascular, gastrointestinal, hepatic, pancreatic, endocrinological, hematological, or immunological disorder or an active infection 17. Any condition possibly affecting drug absorption (e.g., gastrectomy, vagotomy or bowel resection) 18. Estimated glomerular filtration rate (eGFR) 450 milliseconds in males, >460 milliseconds in females) b. atrial fibrillation, atrial flutter, c. notable bradycardia (heart rate 100 bpm) d. complete (left or right) branch block, e. Wolf-Parkinson-White Syndrome, f. cardiac pacemaker 21. Significantly abnormal laboratory tests, including: a. Screening alkaline phosphatase (AP), alanine aminotransferase (SGPT, ALT), aspartate aminotransferase (SGOT, AST), or bilirubin greater than 150% of the upper limit of normal (ULN) b. Screening haemoglobin 200 mL at Screening 23. Clinically significant abnorma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effectiveness of AF-219 in reducing daytime objective cough frequency ;Secondary Objective: To evaluate the effectiveness of AF-219 in: • reducing night time objective cough frequency, • reducing subjective scores of cough severity, • showing global rating of change scale, • improving cough-specific quality of life. To evaluate the safety of AF-219 in a subject population with chronic cough (CC). To evaluate the relationship between AF219 plasma trough concentration and cough relief. ;Primary end point(s): To determine whether 2 weeks of treatment with AF-219 is superior to placebo as measured by change from Baseline in daytime objective cough frequency.;Timepoint(s) of evaluation of this end point: At close of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine whether AF-219 is superior to placebo as measured by change from Baseline in: i. night time objective cough frequency ii. cough VAS day/night iii. urge to cough iv. global rating of change v. cough quality of life;Timepoint(s) of evaluation of this end point: At close of study | — |
Countries
United Kingdom
Contacts
Public ContactStudy Coordinator
Afferent Pharmaceuticals Inc
Outcome results
None listed