A Phase I/IIa, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Safety, and Pharmacokinetics of Single and Multiple Ascending Dose of RP3128 in HV and Effect on LAR to Allergen Challenge in Mild Asthmatics
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
RP3128 is a calcium release activated calcium (CRAC) channel modulator. The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of single and multiple ascending dose(s) of RP3128 in healthy volunteers and to evaluate the effect on late phase asthmatic response to allergen challenge in patients with mild asthma.
详细描述
The study consists of three parts; Part 1: single ascending dose (SAD), Part 2: multiple ascending dose (MAD) in healthy volunteers and Part 3: proof of concept (POC) study in mild asthmatics. There will be 5 cohorts in SAD and 3 cohorts in MAD, the doses used in the MAD will be based on emerging safety, tolerability and pharmacokinetics (PK) from Part 1 (SAD). POC is a randomized, placebo- controlled, double blind, two period cross-over, proof of concept study in male and female of non child bearing potential with history of mild asthma. the highest identified dose of RP3128 in Part 2 (MAD) will be considered for POC
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
- Double (Participant, Investigator)
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
- 是
入选标准
- •Male and non-childbearing female subjects (SAD/MAD) and male and non-childbearing female patients with mild asthma;
- •Healthy subjects as determined by past medical history, vitals, physical examination and 12-lead ECG, clinical laboratory tests.
- •Body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive, weight ≥50 kg;
- •Non-smokers or ex-smokers
- •Willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the subject; able to comply with protocol requirements and or study procedure;
- •Negative screen for drugs of abuse and alcohol at screening and on admission.
- •Male subjects should agree not to donate sperm for 3 months post dose; and
- •Female partners (of child bearing potential) of male subjects should use 2 methods of highly effective contraception for 3 months post last
- •Additionally for POC
- •Pre- bronchodilator Forced expiratory volume in 1 sec( FEV1) of > 70% (adjusted for age, sex and race)
- •Steroid naïve subjects with history of mild asthma that satisfy the Global Initiative for Asthma (GINA) definition of asthma, but otherwise healthy.
排除标准
- •Subjects with evidence or history of clinically significant medical history.
- •History of tuberculosis (TB) and/or a positive Tuberculin Skin Test and/or QuantiFeron- TB®-Gold test.
- •Use of any immunotherapy within 3 months prior to screening.
- •History of serious adverse reaction, severe hypersensitivity or allergy to any drug/drug substance (except house dust mite, pollen allergens or cat dander allergy in asthmatics) or in any other circumstance (e.g. anaphylaxis);
- •Abnormal liver function
- •Positive screen on hepatitis-B surface antigen (HBsAg), antibodies to the hepatitis C (HCV) or antibodies to the human immunodeficiency virus (HIV) 1,2;
研究组 & 干预措施
RP3128
RP3128, A CRAC channel modulator
干预措施: RP3128 (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: Baseline through 2 weeks
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
次要结局
- Cell Count(8 and 24 hours post allergen challenge in Part 3)
- Area Under Effective Concentration (AUEC)(0 to 3 hours and 3 to 8 hours post allergen challenge in Part 3)
- Measurement of Cytokines(Predose and Day 7 in Part 2)
- Fractional Exhaled Nitric Oxide (FeNo)(Prechallenge to 3, 8 and 24 hours post challenge in Part 3)
- Area Under the Plasma-Concentration(Pre-dose through 48 hours post dose)
- Peak Plasma Concentration (Cmax)(Pre-dose through 48 hours post dose)