A Double-Blind, Randomized, Placebo-Controlled, Single- And-Multiple-Dose Study to Evaluate the Safety, PK, and PD of CRN00808 in Healthy Volunteers and to Determine the Effect of CRN00808 on Midazolam PK
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 99
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CRN00808 single ascending doses using clinical assessments, telemetry, and Holter monitoring and subject self-reporting
研究概览
简要总结
This single-center study will be conducted in 3 phases: a single-ascending dose phase (up to 8 cohorts, 8 subjects/cohort), a multiple-dose phase (up to 5 cohorts, 9 subjects/cohort), and a midazolam drug-drug interaction phase (one cohort of 8 subjects).
详细描述
The single-dose phase initiates with ascending doses of an oral solution followed by a 3-way crossover food effect and bioavailability (capsule formulation) cohort. Serum IGF-1 levels and GHRH-analog stimulated GH levels will be assessed as pharmacodynamics measures.
The first multiple-dose (7 days dosing) cohort will be initiated after the PK and safety data are available from the single-dose phase. Subsequent multiple-dose cohorts will have 10 days of dosing. Serum IGF-1 level and GH levels will be assessed as pharmacodynamics measures.
The last cohort in the study is midazolam drug-drug interaction study. The dose will be selected based on review of all pharmacokinetic and safety data for the single-dose and multiple-dose cohorts completed. On Day 1, 8 subjects will receive a single oral 2 mg dose of midazolam. Starting on Day 3 through Day 8, subjects will receive daily doses of CRN00808. On Day 9, subjects will be administered CRN00808 and 2 mg midazolam together.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind study
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI 18 to 30 kg/m2
- •Females postmenopausal or surgically sterile
排除标准
- •Any uncontrolled or active major systemic disease including, but not limited to: acromegaly (with or without pituitary surgery or radiation therapy), cardiac, pulmonary, gastrointestinal, metabolic, urogenital, neurological, immunological, psychiatric, or neoplastic disorder with metastatic potential
- •History or presence of malignancy within the past 5 years. Subjects who have been successfully treated (for 3 months or longer) with no recurrence of basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix may be enrolled.
- •Use of any investigational drug within the past 60 days or 5 half-lives, whichever is longer
- •Have a medically significant abnormality observed during screening or the admission physical examination or in any other baseline measurements
- •Use of any prior medication without approval of the investigator within 14 days prior to admission
- •Tested positive at screening for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV-Ab) or has a history of a positive result
- •History of alcohol or substance abuse in the past 6 months
- •Any condition that in the opinion of the investigator would jeopardize the subject's appropriate participation in this Phase 1 study
研究组 & 干预措施
CRN00808 Oral Solution
CRN00808 oral solution, single-dose
干预措施: CRN00808 (Drug)
CRN00808 Oral Capsule
CRN00808 oral capsule, single-dose and multiple-doses
干预措施: CRN00808 (Drug)
Placebo Oral Solution
Placebo oral solution, single-dose
干预措施: Placebo Oral Solution (Drug)
Placebo Oral Capsule
Placebo oral capsule, single-dose and multiple doses
干预措施: Placebo oral capsule (Drug)
Midazolam Oral Solution
Midazolam oral solution, two single-doses as part of the drug-drug interaction arm of the study
干预措施: CRN00808 (Drug)
Midazolam Oral Solution
Midazolam oral solution, two single-doses as part of the drug-drug interaction arm of the study
干预措施: Midazolam oral solution (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CRN00808 single ascending doses using clinical assessments, telemetry, and Holter monitoring and subject self-reporting
时间窗: Day 1 through Day 10
ECG, clinical laboratory parameters, vital signs, physical examinations, telemetry, Holter monitoring
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CRN00808 multiple ascending doses using clinical assessments and subject self-reporting
时间窗: Day 1 through Day 21
ECG, clinical laboratory parameters, vital signs, physical examinations
次要结局
- AUC of CRN00808 single ascending doses(Day 1 through Day 7)
- Effect of CRN00808 on Cmax of midazolam(Day 1 through Day 10)
- Relative bioavailability of capsule formulation(Day 1 to Day 7)
- Cmax of CRN00808 multiple ascending doses(Day 1 through Day 20)
- Pharmacodynamics of CRN00808 in single ascending dose cohorts assessed by GHRH analog stimulated GH levels(Day -1 and Day 1)
- Effect of CRN00808 on pharmacokinetics of midazolam(Day 1 through Day 10)
- Effect of food on Cmax of CRN00808(Day 1 to Day 7)
- Tmax of CRN00808 single ascending doses(Day 1 through Day 7)
- Tmax of CRN00808 multiple ascending doses(Day 1 through Day 20)
- Pharmacodynamics of CRN00808 in multiple ascending dose cohorts assessed by serum IGF-1 and GH(Day -1 to Day 21)
- AUC of CRN00808 multiple ascending doses(Day 1 through Day 20)
- t1/2 of CRN00808 multiple ascending doses(Day 1 through Day 20)
- Cmax of CRN00808 single ascending doses(Day 1 through Day 7)
- t1/2 of CRN00808 single ascending doses(Day 1 through Day 7)
- Effect of CRN00808 on t1/2 of midazolam(Day 1 through Day 10)
- Effect of CRN00808 on Tmax of midazolam(Day 1 through Day 10)
- Effect of food on AUC of CRN00808(Day 1 to Day 7)