Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001020774
Ethics application status
Approved
Date submitted
10/07/2022
Date registered
21/07/2022
Date last updated
4/08/2023
Date data sharing statement initially provided
21/07/2022
Date results information initially provided
4/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of ONC201 on Cardiac Repolarization in Healthy Participants - Part 2
Scientific title
A Randomized, Positive- and Placebo-Controlled Study to Evaluate the Effects of ONC201 on Cardiac Repolarization in Healthy Participants - Part 2
Secondary ID [1] 307530 0
ONC201-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 326959 0
Solid Tumours 326960 0
Abnormal cardiac repolarization 326961 0
Condition category
Condition code
Cancer 324142 324142 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ONC201 (investigational drug) will be dosed, as a 125mg capsule orally
Part 2:
30 x Healthy Volunteers will be dosed on 3 separate occasions (7 days apart) with each of ONC201 (dose to be determined from Part 1), Placebo and control treatment.
Adherence to intervention will be via mouth check of swallowed capsule
Intervention code [1] 323991 0
Treatment: Drugs
Comparator / control treatment
Part 2: Healthy Volunteers will receive the following control treatments in addition to ONC201 capsules: Treatment A matched placebo capsule (microcellulose capsule) once only (negative control) and Treatment B moxifloxacin 400 mg capsules once only (positive control).
Adherence to intervention will be via mouth check of swallowed capsule
Control group
Active

Outcomes
Primary outcome [1] 331957 0
Assess the effects of ONC201 on cardiac repolarization
Timepoint [1] 331957 0
ECGs - on Day -1, Day 1, and Day 3 post dose in each period, and at Day 14. On Day 1, safety ECGs will be acquired pre-dose(. 1 hour prior to dosing) and at approximately 0.75, 1.0, 2, 4,75, 5, and 6 hours post dose in each treatment period.
Secondary outcome [1] 411732 0
Establish assay sensitivity - Relationship between the plasma concentration of moxifloxacin and the change from baseline for QTcF in order to demonstrate assay sensitivity
Timepoint [1] 411732 0
ECGs - on Day -1, Day 1, and Day 3 post dose in each period, and at Day 14. On Day 1, safety ECGs will be acquired pre-dose(= 1 hour prior to dosing) and at approximately 0.75, 1.0, 2, 4,75, 5, and 6 hours post dose in each treatment period.
PK parameters: (AUClast, AUCinf, Cmax, Tmax, t1/2, CL/F, Vz/F, Clast, Tlast, MPR Cmax, MPR AUClast, MPR AUCinf) measured at the following timepoints - Predose (within 15 minutes prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 4.25, 4,5. 4,75, 5, 5,5, 6, 8, 10, 12, 14, 16, 24, 36 and 48, hours post each dose
Secondary outcome [2] 411733 0
To evaluate the safety and tolerability of ONC201 in healthy adult participants.
Timepoint [2] 411733 0
Clinical and laboratory safety parameters including:
-adverse events (AEs) such as Fatigue, headache, nausea and vomiting - continuously Screening through to Day 14 via physical examination and subject reported events.
For each dosing period:
non absolute and changes over time of hematology and clinical chemistry - at Screen. Day -1, Day 3 and Day 14 post each dose
Vital signs (pulse, Blood pressure.temperature and respiratory rate) using an automated vital sign machine- at Screen, Day -1, Day 2, Day 3 and Day 14 post dose
Neurological assessments (NANO assessment) at Day -1, Day 2, Day 3 and Day 14 post dose
ECG intervals at Screen, Day -1, Day 1, Day 2, Day 3 and Day 14 post dose
Secondary outcome [3] 411734 0
To assess the Cmax, Tmax, AUClast, AUCinf, %AUCextrap, t1/2, CL/F, Vz/F of ONC201 and its metabolite, ONC207, following administration orally in healthy participants
Timepoint [3] 411734 0
PK samples: Blood samples will be taken predose (within 15 minutes prior to dosing) and at 0.25, 0.5, 0.75, 1, 1,5, 2, 2,5. 3, 4, 4.25, 4,5. 4,75, 5, 5,5. 6, 8, 10, 12, 14, 16, 24, 36 and 48 hours post each dose
Secondary outcome [4] 412053 0
Assess the effects of ONC201 on other ECG parameters relative to a moxifloxacin positive control and to placebo:
Change-from-baseline heart rate (HR), QTcF, PR, and QRS intervals using by-time point analysis
• Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS intervals
• Categorical outliers for QTcF, HR, PR, and QRS intervals
• T-wave morphology and U-wave presence changes
Timepoint [4] 412053 0
ECGs - on Day -1, Day 1, and Day 3 post dose in each period, and at Day 14. On Day 1, safety ECGs will be acquired pre-dose(= 1 hour prior to dosing) and at approximately 0.75, 1.0, 2, 4,75, 5, and 6 hours post dose in each treatment period.
PK parameters: (AUClast, AUCinf, Cmax, Tmax, t1/2, CL/F, Vz/F, Clast, Tlast, MPR Cmax, MPR AUClast, MPR AUCinf) measured at the following timepoints - Predose (within 15 minutes prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 4.25, 4,5. 4,75, 5, 5,5, 6, 8, 10, 12, 14, 16, 24, 36 and 48, hours post each dose

Eligibility
Key inclusion criteria
Male or female between 18 to 45 years of age
Female must be of non-childbearing potential
Body weight greater than 50 kg, body mass index between 18-30 kg/m2
Healthy Volunteers who are overtly healthy as determined by medical evaluation and judgment of the investigator including medical history, PE, laboratory tests, vital signs, and cardiac monitoring.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Have a positive serological test result at the screening evaluation consistent with possible infection with HBV, HCV, or HIV.
Have a positive pregnancy test at screening or Period 1 Day -1
Current history of moderate to heavy tobacco/nicotine use
Abnormal 12-lead ECG at Screening or Period 1 Day -1,
Resting supine heart rate less than 45 beats per minute or greater than 100 beats per minute
Any clinically significant abnormal findings during physical examination or medical history

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Random generation by paper randomisation code to order of treatments
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Volunteers will be randomized to one of 6 treatment sequences according to a Williams design for a 3-way crossover design with a minimum 7-day washout period between doses. Only ONC201 will be blinded with a placebo. Moxifloxacin will be administered open label.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
The primary analysis for Part 2 will be based on concentration-OTc modeling of the relationship between ONC201 (and its metabolite ONC207) and change-from-baseline OTcF (change OTcFl)
Safety data will be analyzed descriptively using frequencies of events or continuous statistical summaries

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/08/2022
Actual
14/02/2023
Date of last participant enrolment
Anticipated
31/10/2022
Actual
3/04/2023
Date of last data collection
Anticipated
31/12/2022
Actual
11/05/2023
Sample size
Target
30
Accrual to date
Final
30
Recruitment outside Australia
Country [1] 24885 0
New Zealand
State/province [1] 24885 0
Christchurch

Funding & Sponsors
Funding source category [1] 311807 0
Commercial sector/Industry
Name [1] 311807 0
Chimerix, Inc.
Country [1] 311807 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Chimerix, Inc.
Address
2505 Meridian Parkway, Suite 100, Durham, NC USA 27713
Country
United States of America
Secondary sponsor category [1] 313282 0
None
Name [1] 313282 0
Address [1] 313282 0
Country [1] 313282 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311251 0
NZ Health & Disability Ethics Committee
Ethics committee address [1] 311251 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
New Zealand
Ethics committee country [1] 311251 0
New Zealand
Date submitted for ethics approval [1] 311251 0
20/07/2022
Approval date [1] 311251 0
22/08/2022
Ethics approval number [1] 311251 0

Summary
Brief summary
The purpose of part 2 of this study is to:
• Evaluate how safe and well tolerated ONC201 is, in healthy participants.
• Evaluate the effects of ONC201 on cardiac repolarisation in healthy participants
• Assess the effects of ONC201 on ECG (Electrocardiograms that measure the electrical activity of your heart) compared with moxifloxacin and placebo
• Measure the body’s response to either a single 750 mg dose or two 625 mg doses of ONC201
This study will be conducted in two parts.
Part 2 will enroll approx. 30 participants and each participant will receive each of (in a cross over design, with 7 days between treatments):
A. Placebo (Negative Control) to match
B. Moxifloxacin (Positive Control) 400 mg, single oral dose
C. ONC201 (dose to be determined based on results of Part 1).
For both parts participants will be housed in the clinic on Day -1 through to Day 3.
Part 2 - will consist of a screening period of up to 28 days, 3 times in-house periods, Day -1 to Day 3, separated by at least 7 days, and a Follow up visit at Day 14 post last dose
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120462 0
Dr Alex Cole
Address 120462 0
New Zealand Clinical Trials - Christchurch
264 Antigua Street
Christchurch 8140
Country 120462 0
New Zealand
Phone 120462 0
+64 27 421 4317
Fax 120462 0
NA
Email 120462 0
alex.cole@nzcr.co.nz
Contact person for public queries
Name 120463 0
Dr Alex Cole
Address 120463 0
New Zealand Clinical Trials - Christchurch
264 Antigua Street
Christchurch 8140
Country 120463 0
New Zealand
Phone 120463 0
+64 3 3729477
Fax 120463 0
NA
Email 120463 0
alex.cole@nzcr.co.nz
Contact person for scientific queries
Name 120464 0
Dr Alex Cole
Address 120464 0
New Zealand Clinical Trials - Christchurch
264 Antigua Street
Christchurch 8140
Country 120464 0
New Zealand
Phone 120464 0
+64 3 3729477
Fax 120464 0
NA
Email 120464 0
alex.cole@nzcr.co.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.