A 12 week study to assess the efficacy and safety of AF-219 in patients with long term cough

Phase 1

• Conditions: Chronic Cough; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2015-005064-42-GB
• Lead Sponsor: Afferent Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-12-02
• Study Completion: 2016-11-04
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 253

Inclusion Criteria

Subjects who meet all of the following criteria will be included in the study:
1. Women and Men between 18 and 80 years of age inclusive
2. Have a diagnosis of refractory chronic cough or unexplained cough for at least one year (see ACCP/BTS guidelines in Appendix 1)
3. Have a score of = 40mm on the Cough Severity VAS at Screening
4. 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.
5. 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.
6. Have provided written informed consent.
7. Are willing and able to comply with all aspects of the protocol.

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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

Subjects are NOT eligible for this study if they meet any of the following 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 females
b. Atrial fibrillation or atrial flutter
c. 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
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, o

Study & Design

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