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

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

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

Study Overview

• Status: Terminated
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: ACH-000029; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cameron Johnson; Phone Number: +61 3 9076 8906; Email: c.johnson@nucleusnetwork.com.au

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Pty Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Syneos Health
• Collaborators: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2022
• Primary Completion (Actual): November 2, 2022
• Study Completion (Actual): November 2, 2022

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: May 2, 2022
• First Posted (Actual): May 6, 2022

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: X07-201-00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No