Stable Asthma MedDRA version: 17.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Code: AF-219
Pharmaceutical Form: Tablet
INN or Proposed INN: Not available
Current Sponsor code: AF-219
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5
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. Age between 18 and 65 years, inclusive. 2. Women of child bearing potential (i.e., women who are not surgically sterile, not having had hysterectomy, bilateral tubal occlusion or bilateral oophorectomy, or are not post-menopausal) must have a negative pregnancy test at Screening and prior to randomisation. Definition of postmenopausal status is having been naturally (spontaneously) amenorrhoeic for more than 12 months with an appropriate clinical profile, eg, age appropriate, history of vasomotor symptoms. Women of child-bearing potential must be using 2 forms of acceptable birth control method from Screening through the Follow-Up Visit. Acceptable birth control methods include (of which 2 must be used): • established use of oral, injected or implanted hormonal methods of contraception; • intrauterine device (IUD) or intrauterine system (IUS); • Condom with spermicide • Diaphragm with spermicide 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. 3. Male subjects with partners of child-bearing potential (as defined in Inclusion No. 2) must use 2 methods of acceptable birth control with their partner, 1 of which must be a barrier method. Contraception must start from screening and continue until 3 months after last dose of study drug 4. Non-smokers or former smokers, who stopped smoking 6 months prior to screening. Former smokers should not have a smoking history of more than 5pack years (1 pack of 20 cigarettes per day over 5 years). 5. Pre-bronchodilator (after abstaining from Short acting ß2-agonist for =8 hrs) Forced Expiratory Volume (FEV1) =70% of the predicted normal value at the initial screening visit for the purposes of eligibility. 6. Pre-bronchodilator (after abstaining from Short acting ß2-agonist for =8 hrs) Forced Expiratory Volume (FEV1) =70% of the predicted normal value OR if less than 70% must be within +/- 12 % of screening FEV1 prior to randomization. NB: This visit must not be rescheduled if criteria are not met. 7. Physician documented history or diagnosis of asthma for at least 6 months prior to screening according to the Global Initiative in Asthma guidelines (GINA, 2012). 8. Requires the use of Short acting ß2-agonist therapy only (= 8 puffs per day) for at least 4 weeks prior to screening and prior to randomisation. 9. Positive response to methacholine challenge (PC20 = 8 mg/mL) at screening. 10. Positive response to ATP challenge (PC20 = 200 µmol/mL) at screening. 11. Have provided written informed consent 12. 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: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 19 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: Subjects are NOT eligible for this study if they meet any of the following criteria: 1. Has been hospitalised or attended the emergency department for an asthma attack in the 12 months prior to screening. 2. Exacerbation of asthma or Lower respiratory tract infection during the 4 weeks before screening or prior to randomisation 3. Upper respiratory tract infection during the 4 weeks before screening or prior to randomization requiring treatment with antibiotics. 4. Inhaled or systemic corticosteroids (oral, intravenous, intramuscular) within 4 weeks prior to screening or prior to randomisation. 5. Short-acting or long-acting antihistamines within 48hrs or 7 days, respectively, prior to screening. 6. Body mass index (BMI) 8.0% at screening. 16. Any condition possibly affecting drug absorption e.g., gastrectomy, gastroplasty, any type of bariatric surgery, vagotomy, or bowel resection 17. Estimated glomerular filtration rate (eGFR) 160 mm Hg or a diastolic blood pressure >90 mm Hg or Heart rate 110 bpm at screening or prior to randomisation. 19. Clinically significant abnormal electrocardiogram (ECG) at Screening, including any of the following: a. QTcB interval >450 milliseconds in males, >470 milliseconds in females b. Atrial fibrillation or atrial flutter c. Heart rate 110 bpm d. Second degree or third degree (complete) AV block e. Left bundle branch block (including hemiblock)Wolf-Parkinson-White Syndrome 20. Significantly abnormal laboratory tests at Screening, including: a) alkaline phosphatase (AP), alanine aminotransferase (SGPT, ALT), aspartate aminotransferase (AST, SGOT), or bilirubin >150% of the upper limit of normal (ULN) b) hemoglobin < 11 gm/dL in males / < 10 gm/dL in females, white blood cell (WBC) count <2.5x109 /L, neutrophil count <1.5 x10^9 /L, platelet count <100 × 10^9/L c) Positive tests for drugs of abuse at screening or prior to randomisation d) Positive alcohol breath test at screening or prior to randomisation e) Positive tests for human immunodeficiency virus (HIV) or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the PC20 response (concentration of methacholine required to cause at least a 20% fall in lung function) of two dose levels of AF-219 compared with placebo in subjects with asthma after provocation with methacholine.;Secondary Objective: The secondary objectives are to assess the safety and tolerability of a two dose levels of AF-219 compared with placebo after 3.5 days of treatment. The exploratory objective is to assess the response of two dose levels of AF-219 compared with placebo in subjects with asthma after provocation with inhaled ATP. In addition, the relationship between AF-219 plasma concentrations and methacholine and ATP provocation will be explored.;Primary end point(s): The primary efficacy endpoint of this study is methacholine PC20. • This value will be normalised by means of a log (base 2) transformation, • The primary comparison will be : AF-219 300 mg PO BID vs. placebo. • Secondary comparisons are : o AF-219 50 mg PO BID vs placebo o AF-219 300 mg PO BID vs AF-219 50 mg PO BID ;Timepoint(s) of evaluation of this end point: Each methacholine challenge. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include: - Safety (AE, laboratory, Vital Signs, ECG) and PK parameters - Change in FEV1 after methacholine challenge Exploratory endpoints include: - ATP PC20 - Change in FEV1 after ATP challenge - Cough post ATP challenge - Breathlessness (modified BORG scale) post methacholine and ATP challenge;Timepoint(s) of evaluation of this end point: Secondary endpoints: From first drug administration to end of trial. Exploratory endpoints: Each methacholine and ATP challenge. | — |
Countries
United Kingdom
Contacts
Public ContactBruce McCarthy
Afferent Pharmaceuticals, Inc.
Outcome results
None listed