F901318 - A Phase I, Double-Blind, Placebo Controlled, Single Ascending Oral Dose, Safety, Tolerability and Pharmacokinetic Study in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Safety (Adverse events)
研究概览
简要总结
Double blind, placebo controlled, ascending single oral dose, sequential group study. Forty subjects will complete the study in 5 cohorts (Groups A to E), each group consisting of 8 subjects. Each subject will be on study for approximately 6 weeks. Each subject will participate in one treatment cohort only, residing at the Clinical Research Unit (CRU) from Day -1 (the day before dosing) to Day 6 (120 hours post-dose). Each cohort will be dosed in a leading edge design in which two subjects will receive study drug (1 active and 1 placebo) on the first dosing day, and the last 6 will receive study drug (5 active and 1 placebo) on the second dosing day.
All subjects will return for a post-study visit 8 to 10 days after the dose of study medication.
Cohorts will be dosed at 2 weekly intervals. There will be a review of safety data, after the first two subjects have been dosed and before dosing of the subsequent six subjects. There will be a complete review of safety and pharmacokinetic data of each cohort prior to each dose escalation.
详细描述
Male healthy subjects conforming to the selection criteria will be invited to take part in the study.
Screening visit (Visit 1) After giving fully informed, written consent, subjects will attend the clinic.
Subjects will undergo screening within 28 days prior to the first dose administration. Prior to the screening visit, subjects will:
- Refrain from vigorous exercise for 7 days
- Abstain from alcohol for 48 hours
- Subjects will sign the consent form in the presence of a CRU physician prior to any screening procedures being performed. The information recorded for all subjects, regardless of their suitability for the study, will be retained and archived
The following information and procedures will be recorded and performed as part of the screening assessments:
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Subjects will be males of any ethnic origin between 18 and 45 years of age and with a body weight of 60-100 kg inclusive.
- •Subjects must be in good health, as determined by a medical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory evaluations (congenital non haemolytic hyperbilirubinaemia is acceptable).
- •Subjects will have given their written informed consent to participate in the study and to abide by the study restrictions.
排除标准
- •Male subjects who are not willing to use appropriate contraception (such as a condom) during the study and until follow up.
- •Subjects who have received any prescribed systemic or topical medication within 14 days of the dose administration unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety.
- •Subjects who have used any non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the dose administration (with the exception of vitamin/mineral supplements) unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety.
- •Subjects who have received any medications, including St John's Wort, known to chronically alter drug absorption or elimination processes within 30 days of the dose administration unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety.
- •Subjects who are still participating in a clinical study (e.g. attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug (new chemical or biological entity) in the past 3 months.
- •Subjects who have donated any blood, plasma or platelets in the 2 months prior to screening or who have made donations on more than two occasions within the 12 months preceding the dose administration.
- •Subjects with a significant history of drug allergy as determined by the Investigator.
- •Subjects who have any clinically significant allergic disease (excluding non-active hay fever) as determined by the Investigator.
- •Subjects who have a supine blood pressure and supine pulse rate higher than 140/90 mmHg and 100 beats per minute (bpm), respectively, or lower than 90/50 mmHg and 40 bpm, respectively, confirmed by a repeat assessment.
- •Subjects who consume more than 28 units of alcohol per week or who have a significant history of alcoholism or drug/chemical abuse as determined by the Investigator (one unit of alcohol equals ½ pint [285 mL] of beer or lager, one glass [125 mL] of wine, or 1/6 gill [25 mL] of spirits).
- •Subjects with a positive urine drug screen or alcohol breath test result at screening or first admission.
- •Subjects must not have smoked for 3 months prior to first dose administration unless otherwise specified by the Investigator or Sponsor.
- •Subjects with, or with a history of, any clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatric, respiratory, metabolic, endocrine, ocular (including minor trauma) haematological or other major disorders as determined by the Investigator.
- •Subjects who are known to have serum hepatitis, or who are carriers of the hepatitis B surface antigen (HBsAg) or hepatitis C antibody, or who have a positive result to the test for HIV antibodies.
- •Subjects who have an abnormality in the 12-lead ECG that, in the opinion of the Investigator, increases the risk of participating in the study, such as QTcB interval >430 msec, 2nd or 3rd degree atrioventricular block, complete left bundle branch block, complete right bundle branch block or Wolff-Parkinson-White Syndrome, defined as PR<110 msec, confirmed by a repeat ECG.
- •Subjects who, in the opinion of the Investigator, should not participate in the study for any other reason.
研究组 & 干预措施
Cohort A placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo tolerability (Other)
Cohort A active
2 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 safety (Drug)
Cohort A active
2 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 tolerability (Drug)
Cohort A active
2 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 pharmacokinetics (Drug)
Cohort A placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo safety (Other)
Cohort A placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo pharmacokinetics (Other)
Cohort B active
4 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 safety (Drug)
Cohort B active
4 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 tolerability (Drug)
Cohort B active
4 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 pharmacokinetics (Drug)
Cohort B placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo safety (Other)
Cohort B placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo tolerability (Other)
Cohort B placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo pharmacokinetics (Other)
Cohort C active
6 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 safety (Drug)
Cohort C active
6 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 tolerability (Drug)
Cohort C active
6 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 pharmacokinetics (Drug)
Cohort C placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo safety (Other)
Cohort C placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo tolerability (Other)
Cohort C placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo pharmacokinetics (Other)
Cohort D active
8 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 safety (Drug)
Cohort D active
8 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 tolerability (Drug)
Cohort D active
8 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 pharmacokinetics (Drug)
Cohort D placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo safety (Other)
Cohort D placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo tolerability (Other)
Cohort D placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo pharmacokinetics (Other)
Cohort E active
10 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 safety (Drug)
Cohort E active
10 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 tolerability (Drug)
Cohort E active
10 mg/kg orally F901318 safety,F901318 tolerability and F901318 pharmacokinetics
干预措施: F901318 pharmacokinetics (Drug)
Cohort E placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo safety (Other)
Cohort E placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo tolerability (Other)
Cohort E placebo
Matching placebo safety,placebo tolerability and placebo pharmacokinetics
干预措施: Placebo pharmacokinetics (Other)
结局指标
主要结局
Safety (Adverse events)
时间窗: 10 days
Adverse events
次要结局
- Pharmacokinetics (Cmax)(12 hours)
- Tolerability (Adverse events)(10 days)
- Pharmacokinetics (Area under concentration time curve, AUC)(120 hours)