A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Single/Multiple Day Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of 18- Methoxycoronaridine (18-MC HCl) Administered Orally to Normal Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 108
- 试验地点
- 1
- 主要终点
- To assess the safety, using incidence and severity of adverse events, of a single and multiple-day dosing of 18-MC administered orally.
研究概览
简要总结
The primary objective of this study is to assess the safety and tolerability of a single day dosing and a separate multiple day dosing of 18-MC HCl administered orally, each part of the study having a different set of healthy male and female volunteers.
详细描述
This is a Phase 1, double-blind, randomized, placebo-controlled, single day and multiple day dosing, in healthy, non-smoking, male and female volunteers.
Part 1: Single Ascending Dose (SAD)
Seven (7) healthy male and female volunteers will be randomly assigned to receive either 18-MC HCl (n=5) or placebo (n=2) in each cohort. These volunteers will receive 18-MC HCl twice in 1 day (bid).
There are 3 phases: Screening, Enrollment and Follow-Up. All participants will be assessed for safety and tolerability for 28 days. Screening begins when a participant reports to the clinical unit (CU) for a screening visit to undergo safety and compliance assessments on this day. Participants that meet all eligibility criteria will be admitted to the CU on the day prior to receiving study drug. Enrollment begins on Day 1 where participants will receive two doses of study drug for 1 day, will be assessed for 18-MC PK up to 48 hours, and will remain admitted at the CU until Day 3, at which time they will be discharged. For follow-up the participants will return for safety and tolerability assessments at Days 7, 14, 21 and Day 28.
Part 2: Multiple Day Ascending Dose (MAD)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Written informed consent before any study-specific procedures.
- •Healthy male and female volunteers aged 18 to 55 years (inclusive) with suitable veins for cannulation and repeated venipuncture.
- •Female subjects of both childbearing and nonchildbearing potential will be considered, with certain conditions met
- •Female subjects must agree not to breastfeed starting at screening and throughout the study period.
- •Male participants must agree to practice abstinence; be surgically sterilized; or agree to use of a condom, plus effective contraception.
- •Have not smoked or used any tobacco or nicotine-containing products in the 3 months before screening and agree not to smoke during the entire study.
排除标准
- •History of any clinically important disease or disorder that, in the opinion of the investigator, would affect the ability of the participant to participate in the study
- •History or presence of gastrointestinal, hepatic, cardiac, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of study drug.
- •History of gastrointestinal ulcer disease, inflammatory bowel disease, or frequent indigestion symptoms
- •Adequate organ function
- •History of seizures or epilepsy.
- •Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV).
- •Any clinically significant cardiovascular abnormalities
- •Known or suspected history of substance abuse disorder
- •History of alcohol abuse or excessive intake of alcohol
- •Positive screen for drugs of abuse, cotinine (nicotine) or alcohol
- •Has received another new chemical entity (defined as a compound, which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within 30 days
研究组 & 干预措施
18-MC SAD Study
In Part 1, healthy participants will be randomized into cohorts to receive 18-MC HCl or placebo twice in 1 day.
干预措施: 18-MC Compound (Drug)
18-MC MAD Study
In Part 2, healthy participants will be randomized into cohorts to receive 18-MC HCl or placebo twice a day for 7 consecutive days.
干预措施: 18-MC Compound (Drug)
结局指标
主要结局
To assess the safety, using incidence and severity of adverse events, of a single and multiple-day dosing of 18-MC administered orally.
时间窗: Up to 28 days (SAD) and 42 days (MAD)
Safety and tolerability will be assessed by the incidence and severity of adverse events (AEs). An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
次要结局
- Maximum Observed Plasma Concentration (Cmax)(48 post dose - Day 1 and Day 7)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(48 hours post dose - Day 1 and Day 7)
- Area Under the Curve from Time Zero to Last Quantifiable Concentration (AUClast)(AUC(t0-48hr) pg*hr/mL)
- Terminal Elimination Half-Life (t1/2)(48 hours post dose - Day 1 and Day 7)
- As an exploratory objective, the concentration of metabolites in plasma and urine may be determined(Up to 28 days (SAD) and 42 days (MAD))