A study to determine the ability of AF-219 to affect the cough reflex in healthy volunteers and in people affected by long-term coughing
- Conditions
- Chronic CoughTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2015-000464-34-GB
- Lead Sponsor
- Afferent Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 50
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 < 35.0 kg/m2;
5. FEV1 = 80% at Screening (healthy volunteers only);
6. Have an Emax = 4 following the capsaicin challenge at Screening;
7. Be in good general health with no clinically relevant abnormalities based on the medical history, physical examination, clinical laboratory evaluations (hematology, clinical chemistry, and urinalysis), and 12 lead electrocardiogram;
8. Women of child bearing potential (i.e., women who are not surgically sterile, not having had hysterectomy, bilateral tubal occlusion or bilateral oophorectomy, or are not post-menopausal) must have a negative pregnancy test at Screening and prior to randomization. Definition of postmenopausal status is having been naturally (spontaneously) amenorrhoeic for more than 12 months with an appropriate clinical profile, e.g., age appropriate, history of vasomotor symptoms. Women of child-bearing potential must be using 2 forms of acceptable birth control method from Screening until 3 months after the last dose of study drug. Women of child-bearing potential must use 2 methods of acceptable birth control from Screening until 3 months after the last dose of study drug. (acceptable birth control methods are given in section 5.3);
9. Male subjects with partners of child-bearing potential (as defined in Inclusion No. 8) must use 2 methods of acceptable birth control, 1 of which must be a barrier method. Contraception must start from Screening and continue until 3 months after last dose of study drug. Donation of sperm is not permitted from Screening until 3months after the last dose of study drug (acceptable birth control methods are given in section 5.3);
10. Subjects with chronic cough must:
a. Have Treatment Refractory 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 (treatment is defined as any of the following):
i. first-generation antihistamine for post-nasal drip;
ii. oral steroid course for asthma;
iii. twice daily proton pump inhibitor for an adequate period of time (typically 8 weeks) for reflux disease; or
b. Have a cough for which no objective evidence of an underlying trigger can be determined after investigation.
11. Be able to communicate effectively with the Investigator and other study center personnel and agree to comply with the study procedures and restrictions.
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 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22
Subjects will be excluded if any of the following apply:
1. Current smoker;
2. Individuals who have given up smoking within the past 6 months, or those with >20 pack-year smoking history (chronic cough subjects), or >10 pack-year smoking history (healthy subjects);
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 2 months prior to Screening;
4. History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks prior to Screening or prior to randomization;
5. History of opioid use within 1 week prior to Screening or prior to randomization;
6. History of pregabalin, gabapentin or thalidomide use within 2 weeks of the Screening Visit;
7. Requiring concomitant therapy with prohibited medications;
8. History or symptoms of renal disease or renal obstructive disease;
9. History of kidney/bladder stones (nephro/uro-lithiasis) within 5 years of Screening;
10. History of conditions or disorders that predispose to nephrolithiasis such 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;
11. History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (with the exception of < 3 excised basal cell carcinomas);
12. History of a diagnosis of drug or alcohol dependency or abuse within the last 3 years;
13. In the opinion of the Principal Investigator, an uncontrolled or unstable clinically significant neurological, psychiatric, respiratory, cardiovascular, peripheral vascular, gastrointestinal, hepatic, pancreatic, endocrinological, hematological, or immunological disorder or an active infection (discussion with the Afferent Medical Monitor is needed if clarifications are required);
14. Any condition possibly affecting drug absorption (e.g., gastrectomy, gastroplasty, any type of bariatric surgery, vagotomy, or bowel resection);
15. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (using the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) formula [http://mdrd.com/]) at Screening;
16. Screening systolic blood pressure (SBP) >160 mm Hg or a diastolic blood pressure (DBP) >90 mm Hg;
17. Screening Heart rate <40 beats per minute >110 bpm
18. Clinically significant abnormal electrocardiogram (ECG) at Screening, including any of the following:
a. QT (QTcF) interval >450 milliseconds in males, >470 milliseconds in females
b. Atrial fibrillation or atrial flutter
c. Second degree or third degree (complete) AV block
d. Left bundle branch block (including hemiblock)
e. Wolf-Parkinson-White Syndrome
19. Personal or family history of congenital long QT syndrome or family history of sudden death;
20. Cardiac pacemaker;
21. Significantly abnormal laboratory tests at Screening, including:
a. alkaline phosphatase (AP), alanine aminotransferase (ALT, SGPT), aspartate
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method