A Randomised, Double-Blind, Double-Dummy, Placebo-Controlled, Three-Way Cross-over Study to Evaluate the Effect of AF-219 on Methacholine Hyper-Reactivity in Subjects With Asthma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 主要终点
- Provocative Concentration (PC20) After Methacholine Challenge
研究概览
简要总结
This is a randomized, double-blind, double-dummy, placebo-controlled, three-way cross-over, single centre study in participants with asthma undergoing inhalation of methacholine and adenosine triphosphate (ATP) to assess the provocative concentration (PC20) response of two dose levels of gefapixant (AF-219) compared with placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Women of child-bearing potential (WOCBP) (i.e., women who are not surgically sterile, not having had hysterectomy, bilateral tubal occlusion or bilateral oophorectomy, or are not postmenopausal) must have a negative pregnancy test at Screening and prior to randomization. WOCBP 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 participant and condom for male partner with spermicidal) satisfies the requirement for 2 forms of acceptable birth control. When in line with the preferred lifestyle of the participant, true and complete abstinence (not periodic abstinence) is acceptable.
- •Male participants with partners WOCBP (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.
- •Non-smokers or former smokers, who stopped smoking 6 months prior to screening. Former smokers should not have a smoking history of more than 5 pack years (1 pack of 20 cigarettes per day over 5 years).
- •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).
- •Requires the use of Short acting β2-agonist therapy only (≤ 8 puffs per day) for at least 4 weeks prior to screening and prior to randomization.
排除标准
- •Has been hospitalized or attended the emergency department for an asthma attack in the 12 months prior to screening.
- •Exacerbation of asthma or lower respiratory tract infection during the 4 weeks before screening or prior to randomization.
- •Upper respiratory tract infection during the 4 weeks before screening or prior to randomization requiring treatment with antibiotics.
- •Inhaled or systemic corticosteroids (oral, intravenous, intramuscular) within 4 weeks prior to screening or prior to randomization.
- •Short-acting or long-acting antihistamines within 48hrs or 7 days, respectively, prior to screening.
- •Body mass index (BMI) <18 kg/m2 or ≥ 35 kg/m2 at screening.
- •History of kidney/bladder stones (nephro/uro-lithiasis) within 5 years of screening.
- •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.
- •History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including participants with basal cell carcinomas or cervical carcinoma in situ that has been successfully treated surgically).
- •Personal or family history of congenital long QT Interval on ECG (QT) syndrome.
- •Presence of a cardiac pacemaker.
- •History of a diagnosis of drug or alcohol dependency or abuse within approximately the last 3 years.
- •Diagnosis of depression, psychosis, bipolar disorder, or schizoaffective disorder.
- •Participants with diabetes Type I or uncontrolled diabetes Type II or Glycosylated Hemoglobin (HbA1c) > 8.0% at screening.
- •Any condition possibly affecting drug absorption e.g., gastrectomy, gastroplasty, any type of bariatric surgery, vagotomy, or bowel resection.
- •History of cutaneous adverse drug reaction to sulphonamides or signs or symptoms suggestive of anaphylaxis to sulphonamides.
- •Requiring concomitant therapy with prohibited medications at screening or prior to randomization.
- •Pregnant or breastfeeding woman.
- •Donation of sperm from Screening until 3 months after the last dose of study drug.
- •Male participants with pregnant female partners.
- •Treatment with an investigational drug within 30 days or five half-lives preceding the first dose of study medication or plans to take another investigational drug within 30 days of study completion.
- •Donation or loss of 400 mL or more of blood or donations of plasma within eight (8) weeks prior to initial dosing or longer if required by local regulation.
研究组 & 干预措施
Gefapixant 50/ Gefapixant 300/ Placebo
Gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 1, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 2, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Gefapixant 50 mg (Drug)
Gefapixant 50/ Gefapixant 300/ Placebo
Gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 1, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 2, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Gefapixant 300 mg (Drug)
Gefapixant 50/ Gefapixant 300/ Placebo
Gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 1, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 2, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Placebo to mimic 50 mg tablets (Drug)
Gefapixant 50/ Gefapixant 300/ Placebo
Gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 1, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 2, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Placebo to mimic 300 mg tablets (Drug)
Gefapixant 50/ Placebo/ Gefapixant 300
Gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 1, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 2, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Gefapixant 50 mg (Drug)
Gefapixant 50/ Placebo/ Gefapixant 300
Gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 1, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 2, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Gefapixant 300 mg (Drug)
Gefapixant 50/ Placebo/ Gefapixant 300
Gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 1, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 2, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Placebo to mimic 50 mg tablets (Drug)
Gefapixant 50/ Placebo/ Gefapixant 300
Gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 1, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 2, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Placebo to mimic 300 mg tablets (Drug)
Gefapixant 300/ Gefapixant 50/ Placebo
Gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 1, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 2, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Gefapixant 50 mg (Drug)
Gefapixant 300/ Gefapixant 50/ Placebo
Gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 1, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 2, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Gefapixant 300 mg (Drug)
Gefapixant 300/ Gefapixant 50/ Placebo
Gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 1, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 2, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Placebo to mimic 50 mg tablets (Drug)
Gefapixant 300/ Gefapixant 50/ Placebo
Gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 1, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 2, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Placebo to mimic 300 mg tablets (Drug)
Gefapixant 300/ Placebo/ Gefapixant 50
Gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 1, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 2, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Gefapixant 50 mg (Drug)
Gefapixant 300/ Placebo/ Gefapixant 50
Gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 1, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 2, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Gefapixant 300 mg (Drug)
Gefapixant 300/ Placebo/ Gefapixant 50
Gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 1, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 2, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Placebo to mimic 50 mg tablets (Drug)
Gefapixant 300/ Placebo/ Gefapixant 50
Gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 1, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 2, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Placebo to mimic 300 mg tablets (Drug)
Placebo/ Gefapixant 50/ Gefapixant 300
Placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 1, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 2, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Gefapixant 50 mg (Drug)
Placebo/ Gefapixant 50/ Gefapixant 300
Placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 1, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 2, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Gefapixant 300 mg (Drug)
Placebo/ Gefapixant 50/ Gefapixant 300
Placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 1, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 2, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Placebo to mimic 50 mg tablets (Drug)
Placebo/ Gefapixant 50/ Gefapixant 300
Placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 1, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 2, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Placebo to mimic 300 mg tablets (Drug)
Placebo/ Gefapixant 300/ Gefapixant 50
Placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 1, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 2, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Gefapixant 50 mg (Drug)
Placebo/ Gefapixant 300/ Gefapixant 50
Placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 1, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 2, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Gefapixant 300 mg (Drug)
Placebo/ Gefapixant 300/ Gefapixant 50
Placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 1, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 2, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Placebo to mimic 50 mg tablets (Drug)
Placebo/ Gefapixant 300/ Gefapixant 50
Placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 1, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 2, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.
干预措施: Placebo to mimic 300 mg tablets (Drug)
结局指标
主要结局
Provocative Concentration (PC20) After Methacholine Challenge
时间窗: Screening (Day -21 to Day -1) and Day 3
The provocative concentration (PC) of inhaled methacholine required to reduce forced expiratory volume in 1 second (FEV1) by 20% (PC20) was calculated from the methacholine challenge at screening and 2 hours (+15 minutes) post dose on Day 3 of each Treatment Period using a five-breath dosimeter method. The primary endpoint was the methacholine PC20 value normalized by means of a log (base 2) transformation, at 2 dose levels compared with placebo in participants with asthma following provocation with methacholine.
次要结局
- Highest FEV1 After Methacholine Challenge(Screening (Day -21 to Day -1) and Day 3)