Chronic Cough
Conditions
Sponsors
Afferent Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effectiveness of 3 doses of AF-219, as compared to placebo, after 12 weeks of treatment in reducing awake objective cough frequency; Secondary Objective: •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 and 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 ;Primary end point(s): Change from Baseline in Awake Cough Frequency after AF-219 therapy at each dose studied after 12 weeks (Day 84) of treatment;Timepoint(s) of evaluation of this end point: Primary endpoints are evaluated during entire treatment period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary •Change from Baseline in 24-hr objective cough frequency after 12 weeks (Day 84) of treatment •Change from Baseline in Awake objective cough frequency after 4 weeks (Day 28) of treatment •Change from Baseline in Awake objective cough frequency after 8 weeks (Day 56) of treatment •Change from Baseline in 24-hr objective cough frequency after 4 weeks (Day 28) of treatment •Change from Baseline in 24-hr objective cough frequency after 8 weeks (Day 56) of treatment •Change from baseline in awake objective cough frequency at the Follow-Up visit (Day 98) •Cough Severity Visual Analog Scale (VAS) Other Secondary •Awake cough frequency responder endpoints: =30% reduction, =50% reduction, and =70% reduction •24-hr cough frequency responder endpoints: =30% reduction, =50% reduction, and =70% reduction •Change from Baseline in sleep objective cough frequency after 4,8 and 12 weeks (Day 28, 56 and 84) of treatment •Daily Cough Severity Diary (CSD) •Daily Cough Score •Leicester Cough Questionnaire/Leicester Cough Questionnaire (LCQ) •(LCQ): individual Domain and Total scores •Patient's Global Impression of Change (PGIC) •Clinician's Global Impression of Change (CGIC) •Acceptability Questionnaire •Response to taste assessments over time (based on taste questionnaire) ;Timepoint(s) of evaluation of this end point: Secondary endpoints are evaluated during entire treatment period | — |
Countries
United Kingdom, United States
Contacts
Public ContactPeter Butera, Clinical Operations
Afferent Pharmaceuticals, Inc.
Outcome results
None listed