AF219-012

Principal Investigator: Krishna Sundar
Keywords: chronic cough , sleep apnea , cough , sleep Department: Pulmonary
IRB Number: 00088982 Co Investigator:  
Specialty: Pulmonary, Pulmonary
Sub Specialties: Pulmonary, Airway Disorders
Recruitment Status: Recruiting

Contact Information

Scott Sweeten
scott.sweeten@hsc.utah.edu
8015815811

Brief Summary

Primary Objective
• To evaluate the effectiveness of 3 doses of AF-219, as compared to placebo, after 4 and 12 weeks of treatment in reducing awake objective cough frequency
 
Secondary Objectives
 To evaluate the effectiveness of three different doses of AF-219 as compared to placebo
after 4 and 8 weeks of treatment in reducing awake objective cough frequency
 To evaluate the effectiveness of three different doses of AF-219 as compared to placebo
after 4, 8, and 12 weeks of treatment in reducing 24-hour objective cough frequency
 To evaluate the effectiveness of three different doses of AF-219 as compared to placebo
after 4, 8, and 12 weeks of treatment in reducing sleep objective cough frequency
To evaluate the effectiveness of AF-219 in:
o reducing the cough severity measured by a Visual Analog Scale (VAS)
o reducing subjective scores from the cough severity diary (CSD) and daily cough
score (DCS)
o improving cough-specific quality of life
 To evaluate the persistence of the anti-tussive effect once treatment is discontinued
compared with placebo
 To evaluate the safety of AF-219 in a patient population with treatment refractory chronic
cough
 To evaluate the tolerability of the taste effect as measured by discontinuations due to taste
related adverse events

Inclusion Criteria

1. Women and Men between 18 and 80 years of age inclusive
2. Chest radiograph or CT Thorax within the last 5 years not demonstrating any abnormality considered to be significantly contributing to the chronic cough in the opinion of the Principal Investigtor and Afferent Medical Monitor
3. Have a diagnosis of refractory chronic cough or unexplained cough for at least one year (see ACCP/BTS guidelines in Appendix 1)
4. Have a score of ≥ 40mm on the Cough Severity VAS at Screening
5. Women of child-bearing potential must use 2 forms of acceptable birth control method from Screening through the Follow-Up Visit. Acceptable birth control methods include established use of oral, injected, or implanted hormonal methods of contraception; intrauterine device (IUD) or intrauterine system (IUS); tubal ligation; or male sterilization. Double-barrier method (diaphragm
for female subject and condom for male partner with spermicidal) satisfies the requirement for 2 forms of acceptable birth control. When in line with the preferred life style of the subject, true and complete abstinence (not periodic abstinence) is acceptable.
6. Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control, 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.
7. Have provided written informed consent.
8. Are willing and able to comply with all aspects of the protocol.`

Exclusion Criteria

1. Current smoker
2. Individuals who have given up smoking within the past 6 months
3. Initiation of treatment with an ACE-inhibitor within 4 weeks prior to the Baseline Visit (Day 0) or during the study.
4. FEV1/FVC < 60%
5. History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day 0)
6. History of cystic fibrosis or bronchiectasis
7. History of opioid use within 1 week of the Baseline Visit (Day 0)
8. Requiring concomitant therapy with prohibited medications (see Section 6.6)
9. Body mass index (BMI) <18 kg/m2 or ≥ 40 kg/m2
10. History or symptoms of renal disease or renal obstructive disease
11. History of triple phosphate kidney/bladder stones (nephro/uro-lithiasis) 
12. History of conditions or disorders that predispose to nephrolithiasis such as inflammatory bowel disease (i.e., crohn’s disease and active ulcerative colitis) or short bowel syndrome
13. 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
14. History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects with <3 excised basal cell carcinomas)
15. History of a diagnosis of drug or alcohol dependency or abuse within approximately the last 3 years
16. Any condition possibly affecting drug absorption (e.g., gastrectomy, gastroplasty, any type of bariatric surgery, or vagotomy)
17. Screening systolic blood pressure (SBP) >160 mm Hg or a diastolic blood pressure (DBP) >90 mm Hg
18. Clinically significant abnormal electrocardiogram (ECG) at Screening, including any of the following:
a. QTc interval >450 milliseconds in males and >470 milliseconds in femalesAtrial fibrillation or atrial flutter
b. Heart rate <40 beats per minute >110 bpm
19. Personal or family history of congenital long QT syndrome or family history of sudden death
20. Significantly abnormal laboratory tests at Screening, including:
a. alkaline phosphatase (AP), alanine aminotransferase (ALT, SGPT), aspartate aminotransferase (AST, SGOT), or 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 tests for drugs of abuse
d. Positive tests at Screening for viral hepatitis defined by positive immunoglobulin M (IgM) anti-hepatitis A virus (HAV), hepatitis B virus (HepB) sAg, or anti-hepatitis C virus (HCV), human
immunodeficiency virus (HIV)
21. History of cutaneous adverse drug reaction to sulfonamides or signs and symptoms suggestive of anaphylaxis to sulfonamides
22. Pregnant or Breastfeeding
23. Treatment with an investigational drug (except AF-219) or investigational 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
24. Blood donation within 56 days or plasma donation within 7 days prior to dosing
25. 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.