To Assess the Safety, Tolerability and Pharmacokinetics of ACH-000029 in Healthy Subjects
Study Details
Study Description
Brief Summary
Randomized single ascending dose placebo controlled treatment of ACH-000029 administered orally via capsule in healthy volunteers.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: ACH-000029
ACH-000029 will be administered orally via a capsule.
|
| Placebo Comparator: 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). |
Drug: Placebo
Placebo will be administered orally via a capsule.
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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 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]
- 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)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy male or non-childbearing potential female.
-
Surgically sterile male and female.
Exclusion Criteria:
-
Breastfeeding female subjects.
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Clinical abnormal past medical history.
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History of drug and/or alcohol abuse within 2 years prior to screening.
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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.
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History of any significant drug allergy or known or suspected hypersensitivity.
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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).
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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.
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Any history of significant bleeding or hemorrhagic tendencies.
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Any history of difficulty in donating blood.
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The donation of blood or plasma within 30 days prior to the first dose of IMP.
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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.
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Use of tobacco products or daily exposure to second-hand smoke within 2 months prior to the screening visit.
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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.
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Supine HR, after resting for at least 3 minutes, outside the range of 50 to 90 bpm.
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Abnormal ECG findings at screening or check-in.
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History of unexplained syncope, where orthostatic likely event.
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Personal or family history of sudden death or long QT syndrome.
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History of serious mental disorders that, in the opinion of the investigator, would exclude the subject from participating in this trial.
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No permanent place of residence.
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Subjects with active suicidal ideation prior to dosing.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Nucleus Network Pty Ltd | Melbourne | Victoria | Australia | 3004 |
Sponsors and Collaborators
- Syneos Health
- Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- X07-201-00001