Healthy Volunteers
Conditions
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.
Interventions
DRUGACH-000029
ACH-000029 will be administered orally via a capsule.
DRUGPlacebo
Placebo will be administered orally via a capsule.
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Syneos Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 | — |
| 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 | — |
| 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 (Mean corpuscular volume) | 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 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 Urinalysis (Specific gravity) | 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 | 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 |
| 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. |
| 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) |
Countries
Australia
Outcome results
None listed