To Assess the Safety, Tolerability and Pharmacokinetics of ACH-000029 in Healthy Subjects

Phase 1TerminatedNCT05363839

Syneos Health8 enrolled

Overview

Randomized single ascending dose placebo controlled treatment of ACH-000029 administered orally via capsule in healthy volunteers.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Healthy Volunteers

Interventions

ACH-000029DRUG

ACH-000029 will be administered orally via a capsule.

PlaceboDRUG

Placebo will be administered orally via a capsule.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy male or non-childbearing potential female. * Surgically sterile male and female. Exclusion Criteria: * 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.

Locations (1)

Nucleus Network Pty Ltd

Melbourne, Victoria, Australia

Outcomes

Primary Outcomes

Number (%) of subjects experiencing orthostatic hypotension at any timepoint

Orthostatic assessment will be with the criteria ≥ 20 mmHg decrease in SBP and a \> 25 bpm increase in HR from supine to standing.

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Maximum change in timepoint-matched systolic blood pressure and diastolic blood pressure.

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Maximum change in timepoint-matched resting heart rate.

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal clinical laboratory tests (Hemoglobin & mean corpuscular hemoglobin concentration)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal clinical laboratory tests (Hematocrit)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal clinical laboratory tests (Mean corpuscular volume)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal clinical laboratory tests (RBC count)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal clinical laboratory tests (WBC count (absolute and differential))

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal clinical laboratory tests (Platelets)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Data from ClinicalTrials.gov

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Assessment of abnormal clinical laboratory tests (Mean platelet volume)

Time frame: 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)

Time frame: 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)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal clinical laboratory tests (Albumin)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal clinical laboratory tests (Glomerular filtration rate)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal clinical laboratory tests (Globulin)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal clinical laboratory tests (Total bilirubin)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal clinical laboratory tests (Total protein)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Coagulation

Blood sample assessments will include activated partial thromboplastin time, prothrombin time-international normalized ratio.

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal Urinalysis (Bilirubin, blood, glucose, ketones, nitrites, protein)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal Urinalysis (Leukocyte esterase)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal Urinalysis (Microscopic analysis)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal Urinalysis (pH)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal Urinalysis (Specific gravity)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal Vital signs (temperature)

Temperature will be assessed after subject has been in supine position for at least 3 minutes.

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal Vital signs (respiratory rate)

Respiratory rate will be assessed after subject has been in supine position for at least 3 minutes.

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal Vital signs (blood pressure)

Blood pressure will be assessed in supine and standing positions in each position for at least 3 minutes.

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of abnormal Vital signs (heart rate)

Heart rate will be assessed in supine and standing positions in each position for at least 3 minutes.

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of Physical examinations (height)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of Physical examinations (weight)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of Physical examinations (BMI)

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of Physical examinations

Subjects will be visually assessed for any abnormalities with head, eyes, ears, nose and throat; thorax; abdomen; urogenital; skin and mucosae.

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Assessment of Neurological examinations

Subjects will be assessed for any abnormalities and evaluated for mental status, cranial nerves, motor system, reflexes, sensory system, coordination and station and gait.

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

12-lead ECG assessment of PR interval

Change in electrocardiograms

Time frame: Screening (Days -28 to Day -2), Day -1, Day 1, Day 2, Day 4 and end of treatment Day 7

12-lead ECG assessment of QRS duration

Change in electrocardiograms

Time frame: Screening (Days -28 to Day -2), Day -1, Day 1, Day 2, Day 4 and end of treatment Day 7

12-lead ECG assessment of QT interval

Change in electrocardiograms

Time frame: Screening (Days -28 to Day -2), Day -1, Day 1, Day 2, Day 4 and end of treatment Day 7

12-lead ECG assessment of QTc

Change in electrocardiograms

Time frame: Screening (Days -28 to Day -2), Day -1, Day 1, Day 2, Day 4 and end of treatment Day 7

C-SSRS

Subjects will be interviewed to capture the occurrence, severity and frequency of suicide-related thoughts and behaviors.

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Monitoring of adverse events

Any untoward medical occurrence in a subject, whether considered related to the treatment or not.

Time frame: Screening (Days -28 to Day -2) to end of treatment Day 7

Pharmacokinetic assessment 1

Peak Plasma Concentration (Cmax)

Time frame: Day 1 to end of treatment Day 7

Pharmacokinetic assessment 2

Time of peak plasma concentration (Tmax)

Time frame: Day 1 to end of treatment Day 7

Pharmacokinetic assessment 3

Area under the concentration-time curve calculated to the last observable concentration at time (AUCt)

Time frame: Day 1 to end of treatment Day 7

Pharmacokinetic assessment 4

Area under the concentration-time curve from zero to infinity (AUC∞)

Time frame: Day 1 to end of treatment Day 7

Pharmacokinetic assessment 5

Apparent clearance of the drug normalized to body weight (CL/F)

Time frame: Day 1 to end of treatment Day 7

Pharmacokinetic assessment 6

Apparent clearance of the drug normalized to body weight (CL/F)

Time frame: Day 1 to end of treatment Day 7

Pharmacokinetic assessment 7

Terminal-phase elimination half-life (t1/2,z)

Time frame: Day 1 to end of treatment Day 7

Pharmacokinetic assessment 8

Cmax normalized to dose (Cmax/Dose)

Time frame: Day 1 to end of treatment Day 7

Pharmacokinetic assessment 9

Cmax normalized to dose (Cmax/Dose)

Time frame: Day 1 to end of treatment Day 7

Pharmacokinetic assessment 10

AUCt normalized to dose (AUCt/Dose)

Time frame: Day 1 to end of treatment Day 7

Pharmacokinetic assessment 11

AUC∞ normalized to dose (AUC∞/Dose)

Time frame: Day 1 to end of treatment Day 7