Chronic cough
Conditions
Sponsors
Afferent Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Both healthy and chronic cough subjects who meet all of the following criteria will be included in the study: 1. Be informed of the nature of the study and have provided written informed voluntary consent; 2. Be able to speak, read, and understand English; 3. Be males or females, of any race, between 18 and 80 years of age, inclusive; 4. Have a body mass index (BMI) = 18 and =65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: Subjects will be excluded if any of the following apply: 1. History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day 0); 2. Have acute worsening of asthma; 3. Do not cough during the ATP or Capsaicin or Citric acid challenge at screening or only cough twice at the two highest concentrations of the test solution; 4. Demonstrate more than two coughs to inhalation of the normal saline solution during baseline challenge; 5. 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 Screening 6. History of opioid use within 1 week prior to the Baseline visit (Day 0); 7. Requiring concomitant therapy with prohibited medications (see Section 6.5); 8. History or symptoms of renal disease or renal obstructive disease: a. History of kidney/bladder stones (nephro/uro-lithiasis) within 5 years of Screening. b. History of conditions or disorders that predispose to nephrolithiasis such as Type 1 renal tubular acidosis, cystinuria, gout, hyperparathyroidism, inflammatory bowel disease (i.e., ulcerative colitis and Crohn?s disease), short bowel syndrome, or bariatric surgery. c. Estimated glomerular filtration rate (eGFR) 160 mm Hg or a diastolic blood pressure (DBP) >90 mm Hg; 13. Clinically significant abnormal electrocardiogram (ECG) at Screening, including any of the following: a. QT (QTc) interval >450 milliseconds (msec) for males and >470 msec for females; 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. 14. Personal or family history of congenital long QT syndrome or family history of sudden death; 15. Cardiac pacemaker; 16. Significantly abnormal laboratory tests at Screening, including: a. Alkaline phosphatase (AP), alanine aminotransferase (ALT, SGPT), aspartate aminotransferase (AST, SGOT), or total bilirubin >150% of the upper limit of normal (ULN); b. Hemoglobin < 10 gm/dL, WBC count <2500 mm3, neutrophil count <1500 mm3, platelet count <100 × 103/ mm3; c. Positive urine tests for drugs of abuse; d. Positive tests at Screening for viral hepatitis (defined by positive immunoglobulin M (IgM) an
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Primary endpoints are evaluated during entire treatment period;Main Objective: To assess the effect of of a twice daily dose of 100 mg AF-219 on cough reflex sensitivity in both healthy and chronic cough subjects; Secondary Objective: To determine the effect of a twice daily dose of 100 mg AF 219 on cough severity VAS and urge-to-cough VAS in subjects with chronic cough To determine the effect of a twice daily dose of 100 mg AF 219 on cough frequency in subjects with chronic cough To assess the safety and tolerability of AF-219 ; Primary end point(s): Cough reflex sensitivity is measured by standard clinical methodology incorporating capsaicin, citric acid, ATP, and distilled water cough challenges. The standard end points measured in cough challenge testing are the concentrations of the challenge agents inducing 2 or more (C2) and 5 or more coughs (C5). A logC5 is generally regarded as normally distributed within a population, so parametric comparison of paired observations will be made. In experiments where single paired observations are made two-tailed tests will be used. Where multiple comparisons are made, analysis of variance will be used. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety analysis: Clinical safety data from physical examinations, vital signs, 12 lead ECGs, clinical laboratory tests (hematology and clinical chemistry), and AEs/SAEs will be listed and summarized using descriptive statistics; urinalysis results will be listed and crystalluria will be described. ;Timepoint(s) of evaluation of this end point: Secondary endpoints are evaluated during entire treatment period | — |
Countries
United Kingdom
Contacts
Public ContactPeter Butera, Clinical Operations
Afferent Pharmaceuticals, Inc.
Outcome results
None listed