Clinical trial NCT05363839: To Assess the Safety, Tolerability and Pharmacokinetics of ACH-000029 in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Syneos Health
Sponsor class: OTHER
Collaborators: name: Otsuka Pharmaceutical Development & Commercialization, Inc.
First posted: 2022-05-06
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number (%) of subjects experiencing orthostatic hypotension at any timepoint
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Maximum change in timepoint-matched systolic blood pressure and diastolic blood pressure.
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Maximum change in timepoint-matched resting heart rate.
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (Hemoglobin & mean corpuscular hemoglobin concentration)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (Hematocrit)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (Mean corpuscular volume)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (RBC count)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (WBC count (absolute and differential))
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (Platelets)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (Mean platelet volume)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (Anion gap, bicarbonate, calcium, chloride, cholesterol, glucose, magnesium, potassium, sodium, creatinine, uric acid, triglycerides, urea)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: 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)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (Albumin)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (Glomerular filtration rate)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (Globulin)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (Total bilirubin)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal clinical laboratory tests (Total protein)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Coagulation
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal Urinalysis (Bilirubin, blood, glucose, ketones, nitrites, protein)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal Urinalysis (Leukocyte esterase)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal Urinalysis (Microscopic analysis)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal Urinalysis (pH)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal Urinalysis (Specific gravity)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal Vital signs (temperature)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal Vital signs (respiratory rate)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal Vital signs (blood pressure)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of abnormal Vital signs (heart rate)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of Physical examinations (height)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of Physical examinations (weight)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of Physical examinations (BMI)
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of Physical examinations
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Assessment of Neurological examinations
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: 12-lead ECG assessment of PR interval
timeFrame: Screening (Days -28 to Day -2), Day -1, Day 1, Day 2, Day 4 and end of treatment Day 7
measure: 12-lead ECG assessment of QRS duration
timeFrame: Screening (Days -28 to Day -2), Day -1, Day 1, Day 2, Day 4 and end of treatment Day 7
measure: 12-lead ECG assessment of QT interval
timeFrame: Screening (Days -28 to Day -2), Day -1, Day 1, Day 2, Day 4 and end of treatment Day 7
measure: 12-lead ECG assessment of QTc
timeFrame: Screening (Days -28 to Day -2), Day -1, Day 1, Day 2, Day 4 and end of treatment Day 7
measure: C-SSRS
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Monitoring of adverse events
timeFrame: Screening (Days -28 to Day -2) to end of treatment Day 7
measure: Pharmacokinetic assessment 1
timeFrame: Day 1 to end of treatment Day 7
measure: Pharmacokinetic assessment 2
timeFrame: Day 1 to end of treatment Day 7
measure: Pharmacokinetic assessment 3
timeFrame: Day 1 to end of treatment Day 7
measure: Pharmacokinetic assessment 4
timeFrame: Day 1 to end of treatment Day 7
measure: Pharmacokinetic assessment 5
timeFrame: Day 1 to end of treatment Day 7
measure: Pharmacokinetic assessment 6
timeFrame: Day 1 to end of treatment Day 7
measure: Pharmacokinetic assessment 7
timeFrame: Day 1 to end of treatment Day 7
measure: Pharmacokinetic assessment 8
timeFrame: Day 1 to end of treatment Day 7
measure: Pharmacokinetic assessment 9
timeFrame: Day 1 to end of treatment Day 7
measure: Pharmacokinetic assessment 10
timeFrame: Day 1 to end of treatment Day 7
measure: Pharmacokinetic assessment 11
timeFrame: Day 1 to end of treatment Day 7
Secondary outcomes:
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network Pty Ltd
state: Victoria
Study officials:
References: