EUCTR2015-002034-47-GBActive, not recruitingPhase 1
A Study to Assess the Effect of AF-219 on Cough Reflex Sensitivity in Both Healthy and Chronic Cough Subjects
Conditions
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Enrollment
- 36
Study Overview
Brief Summary
No summary available.
Study Design
- Study Type
- Interventional clinical trial of medicinal product
Eligibility Criteria
Inclusion Criteria
- •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 kg/m2;
- •5. FEV1 = 80% at Screening;
- •6. 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;
- •7. Be non-smokers for at least 5 years;
- •8. If a female of child-bearing potential (i.e., have not undergone a hysterectomy or bilateral oophorectomy) or not post-menopausal (defined as no menses for at least 12 months), agree to use 2 forms of acceptable birth control from Screening through the Follow Up Visit; or if a male, they and/or their partner of child-bearing potential agree to use 2 forms of acceptable birth control from Screening through the Follow Up Visit;
- •9. Be able to communicate effectively with the Investigator and other study center personnel and agree to comply with the study procedures and restrictions.
- •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.
- •b. Have a cough for which no objective evidence of an underlying trigger can be determined after investigation.
- •c. Demonstrate significant cough symptoms by a score greater than 20/70 on the Hull Airway Reflux Questionnaire (HARQ)
- •d. Have a Cough Severity VAS = 40 mm at Screening.
- •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 6
Exclusion Criteria
- •Subjects will be excluded if any of the following apply:
- •1. History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day 0);
- •2. Have acute worsening of asthma;
- •3. Do not cough during the ATP or Capsaicin or Citric acid challenge at screening or only cough twice at the two highest concentrations of the test solution;
- •4. Demonstrate more than two coughs to inhalation of the normal saline solution during baseline challenge;
- •5. 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 Screening
- •6. History of opioid use within 1 week prior to the Baseline visit (Day 0);
- •7. Requiring concomitant therapy with prohibited medications (see Section 6.5);
- •8. History or symptoms of renal disease or renal obstructive disease:
- •a. History of kidney/bladder stones (nephro/uro-lithiasis) within 5 years of Screening.
- •b. History of conditions or disorders that predispose to nephrolithiasis such as 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.
- •c. 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.
- •9. History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects with <3 excised basal cell carcinomas);
- •10. History of a diagnosis of drug or alcohol dependency or abuse within approximately the last 3 years;
- •11. Any condition possibly affecting drug absorption (e.g., gastrectomy, gastroplasty, any type of bariatric surgery, vagotomy, or bowel resection);
- •12. Screening systolic blood pressure (SBP) >160 mm Hg or a diastolic blood pressure (DBP) >90 mm Hg;
- •13. Clinically significant abnormal electrocardiogram (ECG) at Screening, including any of the following:
- •a. QT (QTc) interval >450 milliseconds (msec) for males and >470 msec for females;
- •b. Atrial fibrillation or atrial flutter;
- •c. Heart rate <40 beats per minute (bpm) or >110 bpm;
- •d. Second degree or third degree (complete) AV block;
- •e. Left bundle branch block (including hemiblock);
- •f. Wolf-Parkinson-White Syndrome.
- •14. Personal or family history of congenital long QT syndrome or family history of sudden death;
- •15. Cardiac pacemaker;
- •16. Significantly abnormal laboratory tests at Screening, including:
- •a. Alkaline phosphatase (AP), alanine aminotransferase (ALT, SGPT), aspartate aminotransferase (AST, SGOT), or total 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 urine tests for drugs of abuse;
- •d. Positive tests at Screening for viral hepatitis (defined by positive immunoglobulin M (IgM) an
Investigators
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