To Assess the Safety, Tolerability and Pharmacokinetics of ACH-000029 in Healthy Subjects
- Registration Number
- NCT05363839
- Lead Sponsor
- Syneos Health
- Brief Summary
Randomized single ascending dose placebo controlled treatment of ACH-000029 administered orally via capsule in healthy volunteers.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 8
- Healthy male or non-childbearing potential female.
- Surgically sterile male and female.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SAD Cohorts 1 to 3 - Participants Receiving ACH-000029 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. SAD Cohorts 1 to 3 - Participants Receiving Placebo Placebo Each SAD cohort participant will be randomized to receive placebo on a ratio of 3:1 (active: placebo).
- Primary Outcome Measures
Name Time Method Maximum change in timepoint-matched resting heart rate. Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal clinical laboratory tests (Hemoglobin & mean corpuscular hemoglobin concentration) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal clinical laboratory tests (Hematocrit) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal clinical laboratory tests (RBC count) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal clinical laboratory tests (WBC count (absolute and differential)) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal clinical laboratory tests (Platelets) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal clinical laboratory tests (Mean platelet volume) 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) 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) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal clinical laboratory tests (Albumin) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal clinical laboratory tests (Glomerular filtration rate) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal Urinalysis (Specific gravity) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal clinical laboratory tests (Mean corpuscular volume) Screening (Days -28 to Day -2) to end of treatment Day 7 Number (%) of subjects experiencing orthostatic hypotension at any timepoint 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. Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal clinical laboratory tests (Globulin) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal clinical laboratory tests (Total bilirubin) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal clinical laboratory tests (Total protein) Screening (Days -28 to Day -2) to end of treatment Day 7 Coagulation 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) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal Urinalysis (Leukocyte esterase) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal Urinalysis (Microscopic analysis) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal Urinalysis (pH) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of abnormal Vital signs (temperature) 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) 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) 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) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of Physical examinations (weight) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of Physical examinations (BMI) Screening (Days -28 to Day -2) to end of treatment Day 7 Assessment of Physical examinations 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 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 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 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 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) 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 Day 1 to end of treatment Day 7 Peak Plasma Concentration (Cmax)
Pharmacokinetic assessment 2 Day 1 to end of treatment Day 7 Time of peak plasma concentration (Tmax)
Pharmacokinetic assessment 3 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 Day 1 to end of treatment Day 7 Area under the concentration-time curve from zero to infinity (AUC∞)
Pharmacokinetic assessment 5 Day 1 to end of treatment Day 7 Apparent clearance of the drug normalized to body weight (CL/F)
Pharmacokinetic assessment 6 Day 1 to end of treatment Day 7 Apparent clearance of the drug normalized to body weight (CL/F)
Pharmacokinetic assessment 7 Day 1 to end of treatment Day 7 Terminal-phase elimination half-life (t1/2,z)
Pharmacokinetic assessment 8 Day 1 to end of treatment Day 7 Cmax normalized to dose (Cmax/Dose)
Pharmacokinetic assessment 9 Day 1 to end of treatment Day 7 Cmax normalized to dose (Cmax/Dose)
Pharmacokinetic assessment 10 Day 1 to end of treatment Day 7 AUCt normalized to dose (AUCt/Dose)
Pharmacokinetic assessment 11 Day 1 to end of treatment Day 7 AUC∞ normalized to dose (AUC∞/Dose)
12-lead ECG assessment of QTc 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 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 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Nucleus Network Pty Ltd
🇦🇺Melbourne, Victoria, Australia