A Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of IAMA-6 Administered Orally to Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Number of participants with clinical laboratory abnormalities
研究概览
简要总结
The main purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and food effect of IAMA-6 administered orally to healthy adults.
详细描述
The Sponsor's proposed clinical trial is a randomized, double blind, placebo controlled first in human study. This is a single ascending dose (SAD) and multiple ascending dose (MAD) study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and food effect of IAMA-6 administered orally to healthy adults.
The study consists of the following 3 elements:
Part A: Single Ascending Dose
Part A includes up to 6 cohorts of 8 healthy male and female participants, each receiving a single oral dose of IAMA-6 or placebo (6 IAMA-6 and 2 placebo):
- Group A1 (N=8): IAMA-6 Dose 1 (N=6) or Placebo (N=2)
- Group A2 (N=8): IAMA-6 Dose 2 (N=6) or Placebo (N=2)
- Group A3 (N=8): IAMA-6 Dose 3 (N=6) or Placebo (N=2)
- Group A4 (N=8): IAMA-6 Dose 4 (N=6) or Placebo (N=2)
- Group A5 (N=8): IAMA-6 Dose 5 (N=6) or Placebo (N=2)
- Group A6 (N=8): IAMA-6 Dose 6 (N=6) or Placebo (N=2)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Other
- 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
- •Healthy male and female subjects.
- •Aged between 18 and 55 years.
- •Written informed consent; willing and able to comply with procedures.
- •Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
- •Body mass index of 18.0 to 30.0 kg/m2, inclusive; and a total body weight >50 kg up to a maximum of 110 kg.
- •The subject must be willing to return to the study centre for study treatment and study-related follow-up procedures as required by the protocol.
排除标准
- •Current or past history of a clinically significant (as judged by the Investigator) cardiovascular, cerebrovascular, respiratory, gastrointestinal, hematologic, renal, hepatic, immunologic, metabolic, urologic, neurologic, dermatologic, psychiatric, or other major disease/condition, as determined by the Principal Investigator or Designee.
- •Any history of central nervous system problems (e.g. epilepsy, head injury, loss of consciousness).
- •Any history of malignancy in the previous 5 years involving any organ system (other than localised basal cell carcinoma of the skin).
- •Body Mass Index: <18 kg/m2 , or >30 kg/m
- •Abnormal vital signs, including known history of hypertension, resting oxygen saturation <95% by pulse oximetry.
- •ECG at screening or on Day -1 showing QTcF interval >450 msec in males or >470 msec in females, or presence of any clinically significant dysrhythmia.
- •History of hypersensitivity to any medicinal product(s) or severe hypersensitivity/anaphylaxis with unclear aetiology.
- •Any clinically significant abnormal chemistry values.
- •Any clinically significant abnormal haematology values.
- •Blood donation within the past 3 months.
- •Seropositivity for HBsAg, HCV, HIV 1, or HIV
- •Has a positive nasopharyngeal test for SARS-CoV-2 within 48h before unit admission.
- •If female, has a positive highly sensitive urine pregnancy test at Screening or Day
- •If female and of child-bearing potential, and not meeting the approved criteria for highly effective methods of birth control.
- •Receipt of any Investigational Drug within the past 6 months.
- •Use of prescription medication within 14 days prior to dosing and antibiotics within 30 days prior to dosing.
- •Intake of OTC preparations, vitamins, minerals, herbal remedies within 48h prior to dosing.
- •Current smokers or history of smoking in previous 6 months.
- •Current or history of drug, alcohol, nicotine abuse, or excessive coffee (>5 cups/day) or tea drinking (>5 cups/day).
- •Inadequate comprehension of study risks and requirements.
研究组 & 干预措施
Part A: Single Ascending Dose (SAD)
Single oral doses (6 dose cohorts) of IAMA-6 liquid suspension or placebo-to-match IAMA-6 liquid suspension in fasted participants
干预措施: Placebo (Drug)
Part A: Single Ascending Dose (SAD)
Single oral doses (6 dose cohorts) of IAMA-6 liquid suspension or placebo-to-match IAMA-6 liquid suspension in fasted participants
干预措施: IAMA-6 (Drug)
Part B: Food Effect (FE)
Single oral dose (1 dose cohort) of IAMA-6 liquid suspension in fed participants
干预措施: IAMA-6 (Drug)
Part C: Multiple Ascending Dose (MAD)
Multiple oral doses (3 dose cohorts) of IAMA-6 liquid suspension or placebo-to-match IAMA-6 liquid suspension for 7 days in fasted or fed participants
干预措施: IAMA-6 (Drug)
Part C: Multiple Ascending Dose (MAD)
Multiple oral doses (3 dose cohorts) of IAMA-6 liquid suspension or placebo-to-match IAMA-6 liquid suspension for 7 days in fasted or fed participants
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with clinical laboratory abnormalities
时间窗: Through study completion, an average of 1 year
Clinical laboratory test parameters and mean changes from baseline will be descriptively summarized by treatment group and study part (i.e. Part A, Part B and Part C).
Number of participants with adverse events (AEs)
时间窗: From time of the first dose to study completion, an average of 1 year
All AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA; Version 26.1 or later) System Organ Class and Preferred Term. The incidence of the following events will be summarized by treatment group and study part (i.e. Part A, Part B and Part C): * Treatment-emergent AEs (TEAEs). * TEAEs by severity. * TEAEs by causality. * Serious TEAEs.
Number of participants with serious adverse events (SAEs)
时间窗: From time of the first dose to study completion, an average of 1 year
All AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA; Version 26.1 or later) System Organ Class and Preferred Term. The incidence of the following events will be summarized by treatment group and study part (i.e. Part A, Part B and Part C): * Treatment-emergent AEs (TEAEs). * TEAEs by severity. * TEAEs by causality. * Serious TEAEs.
Number of participants with physical examination abnormalities
时间窗: Part A: Baseline and Day 8; Part B: Day 8; Part C: Baseline and Day 14
Physical examinations and mean changes from baseline (when applicable) will be descriptively summarized by treatment group and study part (i.e. Part A, Part B and Part C).
Number of participants with hearing abnormalities
时间窗: Part C: Screening and Day 6
The results of the hearing tests (Part C) will be descriptively summarized by timepoint and the change vs baseline (when applicable) will also be analysed. Hearing tests performed: High Frequency Audiometry (HFA) and Pure Tone Audiometry (PTA).
Number of participants with electrocardiogram (ECG) abnormalities
时间窗: Part A: Baseline and Days 1, 2 and 8; Part B: Days 1, 2 and 8; Part C: Baseline and Days 1-8 and 14
Electrocardiogram measurements and mean changes from baseline will be descriptively summarized by treatment group and study part (i.e. Part A, Part B and Part C).
Number of participants with vital sign abnormalities
时间窗: Part A: Baseline and Days 1, 2 and 8; Part B: Days 1, 2 and 8; Part C: Baseline and Days 1-8 and 14
Vital sign parameters and mean changes from baseline (when applicable) will be descriptively summarized by treatment group and study part (i.e. Part A, Part B and Part C).
次要结局
- T1/2 pharmacokinetic (PK) parameter of IAMA-6 following single and multiple oral doses(Parts A and B: Day 1, Day 2 and Day 3; Part C: Day 1 Day 2, Day 7, Day 8 and Day 9)
- λz pharmacokinetic (PK) parameters of IAMA-6 following single and multiple oral doses(Parts A and B: Day 1, Day 2 and Day 3; Part C: Day 1 Day 2, Day 7, Day 8 and Day 9)
- Sleep assessment(Day 2 (Parts A, B, C), Days 8 and 9 (Part C))
- Cmax pharmacokinetic (PK) parameter of IAMA-6 following single and multiple oral doses(Parts A and B: Day 1, Day 2 and Day 3; Part C: Day 1 Day 2, Day 7, Day 8 and Day 9)
- Tmax pharmacokinetic (PK) parameter of IAMA-6 following single and multiple oral doses(Parts A and B: Day 1, Day 2 and Day 3; Part C: Day 1 Day 2, Day 7, Day 8 and Day 9)
- CL pharmacokinetic (PK) parameters of IAMA-6 following single and multiple oral doses(Parts A and B: Day 1, Day 2 and Day 3; Part C: Day 1 Day 2, Day 7, Day 8 and Day 9)
- AUC(0-t) and AUCτ pharmacokinetic (PK) parameters of IAMA-6 following single and multiple oral doses(Parts A and B: Day 1, Day 2 and Day 3; Part C: Day 1 Day 2, Day 7, Day 8 and Day 9)
- Vd pharmacokinetic (PK) parameters of IAMA-6 following single and multiple oral doses(Parts A and B: Day 1, Day 2 and Day 3; Part C: Day 1 Day 2, Day 7, Day 8 and Day 9)
- Urine volume(Before treatment (Day -1) and after treatment (Day 1 in Part A and Day 7 in Part C) for a 24-hour period)
- Na+ excretion(Before treatment (Day -1) and after treatment (Day 1 in Part A and Day 7 in Part C) for a 24-hour period)
- K+ excretion(Before treatment (Day -1) and after treatment (Day 1 in Part A and Day 7 in Part C) for a 24-hour period)