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

NCT05363839 | Terminated Phase 1 DMC

• 1 other identifier: X07-201-00001
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (49)

• 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.

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

• 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

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

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

• 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)

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

  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.

  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.

  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.

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

• 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

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

  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.

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

• 12-lead ECG assessment of PR interval

  Change in electrocardiograms

  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

  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

  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

  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.

  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.

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

• Pharmacokinetic assessment 1

  Peak Plasma Concentration (Cmax)

  Day 1 to end of treatment Day 7

• Pharmacokinetic assessment 2

  Time of peak plasma concentration (Tmax)

  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)

  Day 1 to end of treatment Day 7

• Pharmacokinetic assessment 4

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

  Day 1 to end of treatment Day 7

• Pharmacokinetic assessment 5

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

  Day 1 to end of treatment Day 7

• Pharmacokinetic assessment 6

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

  Day 1 to end of treatment Day 7

• Pharmacokinetic assessment 7

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

  Day 1 to end of treatment Day 7

• Pharmacokinetic assessment 8

  Cmax normalized to dose (Cmax/Dose)

  Day 1 to end of treatment Day 7

• Pharmacokinetic assessment 9

  Cmax normalized to dose (Cmax/Dose)

  Day 1 to end of treatment Day 7

• Pharmacokinetic assessment 10

  AUCt normalized to dose (AUCt/Dose)

  Day 1 to end of treatment Day 7

• Pharmacokinetic assessment 11

  AUC∞ normalized to dose (AUC∞/Dose)

  Day 1 to end of treatment Day 7

Study Arms (2)

SAD Cohorts 1 to 3 - Participants Receiving ACH-000029

EXPERIMENTAL

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

SAD Cohorts 1 to 3 - Participants Receiving Placebo

PLACEBO COMPARATOR

Each SAD cohort participant will be randomized to receive placebo on a ratio of 3:1 (active: placebo).

Drug: Placebo

Interventions

ACH-000029 DRUG

ACH-000029 will be administered orally via a capsule.

SAD Cohorts 1 to 3 - Participants Receiving ACH-000029

Placebo DRUG

Placebo will be administered orally via a capsule.

Also known as: Matching Placebo

SAD Cohorts 1 to 3 - Participants Receiving Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or non-childbearing potential female.
• Surgically sterile male and female.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Syneos Health: lead
• Otsuka Pharmaceutical Development & Commercialization, Inc.: collaborator

Study Sites (1)

Nucleus Network Pty Ltd

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Interventions

ACH-000029

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: May 6, 2022
• Study Start: May 6, 2022
• Primary Completion: November 2, 2022
• Study Completion: November 2, 2022
• Last Updated: April 27, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)