A study of investigational drug AF-219 and its affect on treating subjects with chronic cough

• Conditions: Subjects with Chronic Cough; MedDRA version: 17.1Level: LLTClassification code 10066656Term: Chronic coughSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2010-024283-18-GB
• Lead Sponsor: Afferent Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-21
• Last Update Posted: 3 November 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

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

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 <60%
5. History of upper respiratory tract infection within 4 weeks of the Baseline Visit
6. History of opioid use within 1 week of the Baseline Visit
7. History of pregabalin use within 4 weeks of the Baseline Visit
8. Body mass index (BMI) <18 or >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) <60 mL/min/1.73 m2 (using the Modification of Diet in Renal Disease [MDRD] formula [http://mdrd.com/])
19. Screening systolic blood pressure greater than 160 mm Hg or a diastolic blood pressure greater than 90 mm Hg
20. Clinically significant abnormal electrocardiogram (ECG) at Screening, including
a. Prolongation of QT/QTc (corrected QT) interval (>450 milliseconds in males, >460 milliseconds in females)
b. atrial fibrillation, atrial flutter,
c. notable bradycardia (heart rate <45 bpm) or tachycardia (HR >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 <10 g/dL,white blood cell (WBC) <2500 mm3, neutrophil count <1500 mm3, platelet count <100 × 103/mm3
c. Screening haemoglobin A1C =7.0
d. Screening microscopic haematuria, defined as =5 red blood count (RBC) per high-power field (hpf) on microscopic urinalysis
22. Post-void residual >200 mL at Screening
23. Clinically significant abnorma

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effectiveness of AF-219 in reducing daytime objective cough frequency<br>;Secondary Objective: To evaluate the effectiveness of AF-219 in:<br>• reducing night time objective cough frequency,<br>• reducing subjective scores of cough severity,<br>• showing global rating of change scale,<br>• improving cough-specific quality of life.<br>To evaluate the safety of AF-219 in a subject population with chronic cough (CC).<br>To evaluate the relationship between AF219 plasma trough concentration and cough relief.<br>;Primary end point(s): To determine whether 2 weeks of<br>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 Outcome Measures

Name	Time	Method
Secondary end point(s): To determine whether AF-219 is superior<br>to placebo as measured by change from Baseline in:<br>i. night time objective cough frequency<br>ii. cough VAS day/night<br>iii. urge to cough<br>iv. global rating of change<br>v. cough quality of life;Timepoint(s) of evaluation of this end point: At close of study