A Phase 1, Single-center, Placebo-controlled, Double-blind, Randomized Trial to Assess the Safety, Tolerability, and Pharmacokinetics of Single Ascending Oral Doses of ACH-000029 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Maximum change in timepoint-matched resting heart rate.
研究概览
简要总结
Randomized single ascending dose placebo controlled treatment of ACH-000029 administered orally via capsule in healthy volunteers.
详细描述
This study will be conducted in up to 3 dosing groups of 8 total subjects each.
The purpose of this trial is to determine the safety and tolerability of a single dose of ACH-000029 or placebo.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 or non-childbearing potential female.
- •Surgically sterile male and female.
排除标准
- •Breastfeeding female subjects.
- •Clinical abnormal past medical history.
- •History of drug and/or alcohol abuse within 2 years prior to screening.
- •History of or current hepatitis or acquired immunodeficiency syndrome or carriers of hepatitis B surface antigen and/or anti-hepatitis C virus antibodies, or human immunodeficiency virus (HIV) antibodies.
- •History of any significant drug allergy or known or suspected hypersensitivity.
- •A positive urine or breath alcohol test and/or urine drug screen for substances of abuse at screening or upon admission to the trial site (Day -1).
- •Subjects having taken an investigational drug within 30 days prior to screening or a biological investigational product within 30 days or 5 half-lives (whichever is longer) preceding screening, except the last dose of severe acute respiratory syndrome coronavirus (SARS-CoV-2 [COVID-19]) vaccine, which must be administered at least 7 days prior to screening.
- •Any history of significant bleeding or hemorrhagic tendencies.
- •Any history of difficulty in donating blood.
- •The donation of blood or plasma within 30 days prior to the first dose of IMP.
- •Use of prescription, over-the-counter, or herbal medications or vitamin supplements within 14 days prior to the first dose of IMP and oral antibiotics within 30 days prior to the first dose of IMP.
- •Use of tobacco products or daily exposure to second-hand smoke within 2 months prior to the screening visit.
- •Presenting with, or having a history of, uncontrolled hypertension (SBP > 140 mmHg or DBP > 90 mmHg) or symptomatic hypotension, or orthostatic hypotension, which is defined as a decrease of ≥ 30 mmHg in SBP or a decrease of ≥ 20 mmHg in DBP after at least 3 minutes of standing compared with the previous supine BP, OR development of symptoms.
- •Supine HR, after resting for at least 3 minutes, outside the range of 50 to 90 bpm.
- •Abnormal ECG findings at screening or check-in.
- •History of unexplained syncope, where orthostatic likely event.
- •Personal or family history of sudden death or long QT syndrome.
- •History of serious mental disorders that, in the opinion of the investigator, would exclude the subject from participating in this trial.
- •No permanent place of residence.
- •Subjects with active suicidal ideation prior to dosing.
研究组 & 干预措施
SAD Cohorts 1 to 3 - Participants Receiving ACH-000029
Each SAD cohort participant will be randomized to receive 10mg for cohort 1; up to 30mg and up to 60mg for cohorts 2 and 3 respectively dependent on dose review committee.
干预措施: ACH-000029 (Drug)
SAD Cohorts 1 to 3 - Participants Receiving Placebo
Each SAD cohort participant will be randomized to receive placebo on a ratio of 3:1 (active: placebo).
干预措施: Placebo (Drug)
结局指标
主要结局
Maximum change in timepoint-matched resting heart rate.
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (Hemoglobin & mean corpuscular hemoglobin concentration)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (Hematocrit)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (RBC count)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (WBC count (absolute and differential))
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (Platelets)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (Mean platelet volume)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (Anion gap, bicarbonate, calcium, chloride, cholesterol, glucose, magnesium, potassium, sodium, creatinine, uric acid, triglycerides, urea)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (Lactate Dehydrogenase (LDH), Alanine Transaminase (ALT), gamma-glutamyl transferase (GGT), Alkaline phosphatase (ALP) , aspartate aminotransferase (AST), phosphatase, creatinine phosphokinase)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (Albumin)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (Glomerular filtration rate)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal Urinalysis (Specific gravity)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (Mean corpuscular volume)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Number (%) of subjects experiencing orthostatic hypotension at any timepoint
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Orthostatic assessment will be with the criteria ≥ 20 mmHg decrease in SBP and a \> 25 bpm increase in HR from supine to standing.
Maximum change in timepoint-matched systolic blood pressure and diastolic blood pressure.
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (Globulin)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (Total bilirubin)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal clinical laboratory tests (Total protein)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Coagulation
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Blood sample assessments will include activated partial thromboplastin time, prothrombin time-international normalized ratio.
Assessment of abnormal Urinalysis (Bilirubin, blood, glucose, ketones, nitrites, protein)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal Urinalysis (Leukocyte esterase)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal Urinalysis (Microscopic analysis)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal Urinalysis (pH)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of abnormal Vital signs (temperature)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Temperature will be assessed after subject has been in supine position for at least 3 minutes.
Assessment of abnormal Vital signs (respiratory rate)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Respiratory rate will be assessed after subject has been in supine position for at least 3 minutes.
Assessment of abnormal Vital signs (blood pressure)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Blood pressure will be assessed in supine and standing positions in each position for at least 3 minutes.
Assessment of Physical examinations (height)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of Physical examinations (weight)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of Physical examinations (BMI)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Assessment of Physical examinations
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Subjects will be visually assessed for any abnormalities with head, eyes, ears, nose and throat; thorax; abdomen; urogenital; skin and mucosae.
Assessment of Neurological examinations
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Subjects will be assessed for any abnormalities and evaluated for mental status, cranial nerves, motor system, reflexes, sensory system, coordination and station and gait.
12-lead ECG assessment of PR interval
时间窗: Screening (Days -28 to Day -2), Day -1, Day 1, Day 2, Day 4 and end of treatment Day 7
Change in electrocardiograms
12-lead ECG assessment of QRS duration
时间窗: Screening (Days -28 to Day -2), Day -1, Day 1, Day 2, Day 4 and end of treatment Day 7
Change in electrocardiograms
12-lead ECG assessment of QT interval
时间窗: Screening (Days -28 to Day -2), Day -1, Day 1, Day 2, Day 4 and end of treatment Day 7
Change in electrocardiograms
Assessment of abnormal Vital signs (heart rate)
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Heart rate will be assessed in supine and standing positions in each position for at least 3 minutes.
Pharmacokinetic assessment 1
时间窗: Day 1 to end of treatment Day 7
Peak Plasma Concentration (Cmax)
Pharmacokinetic assessment 2
时间窗: Day 1 to end of treatment Day 7
Time of peak plasma concentration (Tmax)
Pharmacokinetic assessment 3
时间窗: Day 1 to end of treatment Day 7
Area under the concentration-time curve calculated to the last observable concentration at time (AUCt)
Pharmacokinetic assessment 4
时间窗: Day 1 to end of treatment Day 7
Area under the concentration-time curve from zero to infinity (AUC∞)
Pharmacokinetic assessment 5
时间窗: Day 1 to end of treatment Day 7
Apparent clearance of the drug normalized to body weight (CL/F)
Pharmacokinetic assessment 6
时间窗: Day 1 to end of treatment Day 7
Apparent clearance of the drug normalized to body weight (CL/F)
Pharmacokinetic assessment 7
时间窗: Day 1 to end of treatment Day 7
Terminal-phase elimination half-life (t1/2,z)
Pharmacokinetic assessment 8
时间窗: Day 1 to end of treatment Day 7
Cmax normalized to dose (Cmax/Dose)
Pharmacokinetic assessment 9
时间窗: Day 1 to end of treatment Day 7
Cmax normalized to dose (Cmax/Dose)
Pharmacokinetic assessment 10
时间窗: Day 1 to end of treatment Day 7
AUCt normalized to dose (AUCt/Dose)
Pharmacokinetic assessment 11
时间窗: Day 1 to end of treatment Day 7
AUC∞ normalized to dose (AUC∞/Dose)
12-lead ECG assessment of QTc
时间窗: Screening (Days -28 to Day -2), Day -1, Day 1, Day 2, Day 4 and end of treatment Day 7
Change in electrocardiograms
C-SSRS
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Subjects will be interviewed to capture the occurrence, severity and frequency of suicide-related thoughts and behaviors.
Monitoring of adverse events
时间窗: Screening (Days -28 to Day -2) to end of treatment Day 7
Any untoward medical occurrence in a subject, whether considered related to the treatment or not.
次要结局
未报告次要终点