A Phase 2a, Single-Blind, Placebo-Controlled, Parallel-Group Study to Assess Safety, Tolerability, and Pharmacokinetics of Brensocatib Tablets in Adults With Cystic Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 14
- 主要终点
- Maximum Plasma Concentration (Cmax) of Brensocatib on Day 1
研究概览
简要总结
The main objective of the study is to evaluate the pharmacokinetics of brensocatib in participants with cystic fibrosis following once daily oral administration of study drug and to evaluate the safety of brensocatib compared to placebo in participants with cystic fibrosis (CF) over the 4-week treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be ≥18 years of age at the time of signing the informed consent.
- •Male or female participants with a confirmed diagnosis of CF related lung disease:
- •Percent predicted forced expiratory volume in 1 second (ppFEV1) between 40% to 90% (inclusive) at Screening Visit and at Baseline.
- •Stable CF treatment for at least 30 days before screening and willing to remain on a stable regimen throughout the treatment period.
- •Has a body mass index ≥18 kg/m^
- •Male and female participants must use contraceptives that are consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Male participants, who are not sterile, with female partners of childbearing potential must be using effective contraception from Day 1 to at least 90 days after the last dose.
- •Women must be postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, or using highly effective contraception methods (i.e., methods that alone or in combination achieve <1% unintended pregnancy rates per year when used consistently and correctly) from Day 1 to at least 90 days after the last dose.
- •Female participants of childbearing potential must have a negative serum pregnancy test at Screening.
- •Male participants with pregnant or nonpregnant women of childbearing potential partners must use a condom.
排除标准
- •Severe or unstable CF, per Investigator's judgement.
- •Currently being treated for allergic bronchopulmonary aspergillosis or nontuberculous mycobacteria or tuberculosis.
- •Active and current infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
- •History of malignancy in the past 5 years, except completely treated in situ carcinoma of the cervix and completely treated non-metastatic squamous or basal cell carcinoma of the skin.
- •Established diagnosis of hepatitis B viral infection or positive for hepatitis B surface antigen (HBsAg) at Screening.
- •Established diagnosis of hepatitis C virus (HCV) infection at Screening. Participants positive for hepatitis C antibody are eligible only if HCV RNA is negative.
- •History of human immunodeficiency virus (HIV) infection.
- •Acute upper or lower respiratory tract infection, pulmonary exacerbation, or changes in therapy (including intravenous and oral antibiotics) for pulmonary disease within 4 weeks prior to Day 1 (administration of the first dose of study drug). Participants meeting this criterion could be rescreened 4 weeks after resolution of symptoms.
- •History of prolonged QT/QTc interval with QTcF >480 millisecond (msec) at Screening.
- •History of solid organ or hematological transplantation.
- •Have diagnosed periodontal disease and are either:
- •Currently treated by a dentist for this condition or
- •Expected to have periodontal disease-related procedures within the study period.
- •Received any live attenuated vaccine within 4 weeks prior Screening.
- •Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 90 days prior to Screening.
- •Known history of hypersensitivity to brensocatib or any of its excipients.
- •Use of any immunomodulatory agents within 4 weeks before the Screening Visit is prohibited during the study through end of study (including, but not limited to: bortezomib, ixazomib, thalidomide, cyclophosphamide, mycophenolate, Janus kinase inhibitors, interferon gamma (IFN-γ], and azathioprine).
- •Continuous use of high-dose non-steroidal anti-inflammatory drugs (NSAIDs) is prohibited during the study through end of study.
- •History of alcohol, medication, or illicit drug abuse.
- •Current smoker, as defined by Centers for Disease Control and Prevention: An adult who has smoked 100 cigarettes in his or her lifetime and who currently smokes cigarettes.
研究组 & 干预措施
Brensocatib 10 mg
Participants received brensocatib at a dose of 10 mg once per day for 28 days.
干预措施: Brensocatib (Drug)
Brensocatib 25 mg
Participants received brensocatib at a dose of 25 mg once per day for 28 days.
干预措施: Brensocatib (Drug)
Brensocatib 40 mg
Participants received brensocatib at a dose of 40 mg once per day for 28 days.
干预措施: Brensocatib (Drug)
Placebo
Participants received a placebo matching brensocatib once per day for 28 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Maximum Plasma Concentration (Cmax) of Brensocatib on Day 1
时间窗: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose on Day 1
Cmax of Brensocatib on Day 28
时间窗: Predose and at 0.5, 1, 2, 4, 6, 8, 24, and 168 hours postdose on Day 28
Time to Maximum Plasma Concentration (Tmax) of Brensocatib on Day 1
时间窗: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose on Day 1
Tmax of Brensocatib on Day 28
时间窗: Predose and at 0.5, 1, 2, 4, 6, 8, 24, and 168 hours postdose on Day 28
Area Under the Concentration-time Curve From Time 0 to 24 Hours Postdose (AUC0-24) of Brensocatib in Plasma on Day 1
时间窗: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose on Day 1
AUC0-24 of Brensocatib in Plasma on Day 28
时间窗: Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hours postdose on Day 28
Elimination Half-life (t1/2) of Brensocatib in Plasma on Day 28
时间窗: Predose and at 0.5, 1, 2, 4, 6, 8, 24, and 168 hours postdose on Day 28
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)
时间窗: Up to Day 56
A TEAE is defined as any adverse event (AE) that occurred after the first dose of study investigational medicinal product (IMP) and within 28 days after the last dose of study IMP.
次要结局
- Dose Proportionality of Brensocatib for Dose Levels 10mg to 40mg Using Brensocatib Cmax After Administration of Brensocatib on Days 1 and 28(Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 and 168 hours postdose)
- Dose Proportionality of Brensocatib for Dose Levels 10mg to 40mg Using Brensocatib AUC0-24 After Administration of Brensocatib on Days 1 and 28(Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hours postdose)
- AUClast of Brensocatib in Plasma on Days 1 and 28(Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 and 168 hours postdose)
- Dose Proportionality of Brensocatib for Dose Levels 10mg to 40mg Using Brensocatib AUClast, After Administration of Brensocatib on Days 1 and 28(Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 and 168 hours postdose)