A Two-Part Study Designed to Evaluate the Pharmacokinetic Profile of MIN-101 and Its Main Metabolites Following Single and Multiple Dose Modified Release Prototype Formulation Administration in Healthy Cytochrome P450 2D6 Extensive Metabolizer Male and Female Subjects, and to Evaluate the Relationship Between the Pharmacokinetic Profile of MIN-101 and Its Main Metabolites and Cardiovascular Parameters.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Part 1 Pharmacokinetic profile of MIN-101 and its main metabolites (AUC (0-last), Tmax, Cmax, AUC (0-inf), %AUCextrap, Lambda z, T1/2 and parent:metabolites ratio
研究概览
简要总结
The aim of the study is to assess how MIN-101 is taken up by the body when given in different amounts and in different formulations. The drug will be given as a single dose in Part 1 of the study and during Part 2 of the study as multiple dose, once daily for 7 days. The ultimate aim is to find an optimal formulation which can be developed as a once daily dose for the treatment of schizophrenia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
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
- •Healthy males (Part 1 and Part 2) or non-pregnant, non-lactating healthy females (Part 2 only)
- •Body mass index (BMI) of 18.0 to 30.0 kg/m2
- •Must be CYP2D6 Extensive metabolizer
- •Must be willing and able to communicate and participate in the whole study
- •Must provide written informed consent
- •Must agree to use an adequate method of contraception
排除标准
- •Subjects who have QTc > 430 in male, > 450 in female confirmed by a repeat ECG
- •Any family history of sudden cardiac death and Torsade de Points
- •No personal or family history of unexplained presyncope, syncope or orthostatic hypotension
- •History of any drug or alcohol abuse in the past 2 years
- •History or evidence of any medically diagnosed clinically significant psychiatric disorders
- •Suicidal tendencies or history of suicidal attempts
- •Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
- •Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening
- •Females of childbearing potential who are pregnant or lactating (female subjects must have a negative urine pregnancy test at admission)
- •Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator
- •Positive drugs of abuse test result
- •Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
研究组 & 干预措施
Part 1: MIN-101
MIN-101
modified release formulation (MR),single oral dose between 16 and 64 mg
干预措施: MIN-101 (Drug)
Part 2: MIN-101 low dose
MIN-101
single daily oral dose, low dose MR formulation, from Day 1 to Day 7
干预措施: MIN-101 (Drug)
Part 2: placebo
placebo MIN-101
daily oral dose from Day 1 to Day 7
干预措施: Placebo (Drug)
Part 2: MIN-101 high dose
MIN-101
single daily oral dose, low dose MR formulation, from Day 1 to Day 7
干预措施: MIN-101 (Drug)
结局指标
主要结局
Part 1 Pharmacokinetic profile of MIN-101 and its main metabolites (AUC (0-last), Tmax, Cmax, AUC (0-inf), %AUCextrap, Lambda z, T1/2 and parent:metabolites ratio
时间窗: predose and 0.5h, 1h, 1.5h, 2h, 2.5h, 3H, 4H, 6h, 8h, 10h, 12h, 14h, 16h, 20h, 24h, 48h and 72h post-dose
Part 2 - Pharmacokinetic profile of MIN-101 and its main metabolites - Absolute QT intervals and QT intervals corrected using Fridericia formula (QTcF)
时间窗: predose to Day 8
次要结局
- Part 2 Change from baseline in ECG parameters other than QT/QTc(from predose up to Day 8)
- Part 1 Pharmacokinetic profile of MIN-101 in fed and fasted state(from predose up to 72 h post dosing)
- Part 1 Safety and tolerability (incidence of adverse events, safety laboratory, 12-lead ECGs, vital signs, physical examination) -(from predose up to 72 h post dosing)
- Part 2 Change from baseline in heart rate and blood pressure(from predose up to Day 8)
- Part 2 Incidence of QT/QTc changes from baseline greater than 30 and 60 ms post dose(from predose up to Day 8)
- Part 2 Incidence of QTc values greater than 450, 480 and 500 ms post dose(from predose up to Day 8)
- Part 2 Safety and tolerability of MIN-101 (adverse events occurrence, physical examination, safety laboratory tests)(from predose up to Day 8)