A Double-Blind, Placebo Controlled, Phase I Study to Assess Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Oral Doses of GIC-1001 in Normal Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Change in physical status
研究概览
简要总结
The objectives of this single center, randomized, double-blinded, placebo-controlled Phase I clinical study are to evaluate the safety and tolerability of five (5) single and four (4) multiple increasing oral doses of GIC-1001 compared to placebo, and to evaluate the pharmacokinetics of GIC-1001 following single and multiple-dose administration in 80 healthy, 18-50 years old male and female subjects. Moreover, the effect of food on the pharmacokinetics of GIC-1001 in healthy subjects will be assessed. This study is designed with an integrated, adaptive approach which allows the evaluation of single and multiples doses of GIC-1001 in a progressive, overlapped fashion.
详细描述
Each cohort of enrolled healthy volunteers will include a total of eight (8) subjects: Six (6) subjects randomized to the active GIC-1001 and two (2) subjects randomized to a matching placebo.
Part 1: Single Doses Cohort A: Single dose of 125 mg of GIC-1001 or placebo; Cohort B: Single dose of 250 mg of GIC-1001 or placebo; Cohort C: Single dose of 375 mg of GIC-1001 or placebo; Cohort D: Single dose of 500 mg of GIC-1001 or placebo; and Cohort E: Single dose of 1000 mg of GIC-1001 or placebo. Up to 21 blood samples will be obtained over a 36 hour period.
Part 2: Multiple Doses, three times a day (TID) during 7 consecutive days; Cohort F: Multiple doses of 125 mg of GIC-1001 or placebo; Cohort G: Multiple doses of 250 mg of GIC-1001 or placebo; Cohort H: Multiple doses of 375 mg of GIC-1001 or placebo; and Cohort I: Multiple doses of 500 mg of GIC-1001 or placebo. Up to 18 blood samples will be obtained over a 7 day period.
Part 3: one single dose of GIC-1001 to be selected for the Food Effect cross-over evaluation. A total of 16 blood samples will be obtained over a 36 hour period.
Physical exams, 24 hour cardiac monitoring, and a complete battery of biochemical and hematological lab tests will be done to assess the safety and tolerability of GIC-1001 in all dosing cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female volunteer
- •A female volunteer must meet one of the following criteria:
- •Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens from the screening visit until 2 months after the last drug administration.
- •Participant is of non-childbearing potential, defined as a female who had had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)
- •A male volunteer with sexual partners who are pregnant, possibly pregnant, or who could become pregnant must meet the following criterion: Participant agrees to use one of the accepted contraceptive regimens from first drug administration until 3 months after the last drug administration.
- •Volunteer aged of at least 18 years but not older than 50 years
- •Volunteer with a body mass index (BMI) greater than or equal to 18.50 and below 30 kg/m2
- •Non- or ex-smokers. An ex-smoker is defined as someone who completely stopped smoking for at least 6 months before day 1 of this study
- •Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance
- •Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, biochemistry, ECG and urinalysis)
排除标准
- •History of significant hypersensitivity to trimebutine, to sulfur containing drugs (e.g. Captopril) or any related products (including excipients of the formulation) as well as severe hypersensitivity reactions (like angioedema) to any drugs
- •Presence of significant gastrointestinal, liver/kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects
- •History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability
- •Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
- •Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
- •Presence of out-of-range cardiac interval (PR < 110 msec, PR > 200 msec, QRS <60 msec, QRS >110 msec and QTc > 440 msec) on the screening ECG or other clinically significant ECG abnormalities
- •Known presence of rare hereditary problems of galactose and /or lactose intolerance
- •Use of cysteine, methionine, and other sulfur containing amino acid supplements in the previous 7 days before day 1 of this study
- •Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
- •Any clinically significant illness in the previous 28 days before day 1 of this study
- •Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 28 days before day 1 of this study
- •Any history of tuberculosis and/or prophylaxis for tuberculosis
- •Positive urine screening of ethanol and/or drugs of abuse
- •Positive results to HIV, HBsAg or anti-HCV tests
- •Females who are pregnant according to a positive serum pregnancy test
- •Volunteers who took an Investigational Product (in another clinical trial) or donated 50 mL or more of blood in the previous 28 days before day 1 of this study
研究组 & 干预措施
GIC-1001 oral tablets
GIC-1001; 125 mg oral tablets; Single ascending doses (SAD) from 125 mg to 1000 mg; multiple ascending dose (MAD) from 125 mg to 500 mg TID over 7 successive days
干预措施: GIC-1001; 125 mg oral tablets (Drug)
GIC-1001 matching placebo
Matching placebo, single or multiple dosing
干预措施: GIC-1001 matching placebo (Drug)
结局指标
主要结局
Change in physical status
时间窗: 8 hours post- drug administration
Safety and Tolerability Monitoring: changes from baseline in blood pressure, pulse rate, oxygen saturation of blood, and body temperature will be measured at 8 hours post drug administration.
次要结局
- Pharmacokinetics(Up to 36 hours for single ascending doses; every day and up to 8 hour post last dose for multiple ascending doses)
- Change in ECG recording(3 hours post drug administration)
- Cardiac monitoring(23 hours post drug administration)