Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001021763
Ethics application status
Approved
Date submitted
24/06/2022
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 1
Scientific title
A Randomized, Positive- and Placebo-Controlled Study to Evaluate the Effects of ONC201 on Cardiac Repolarization in Healthy Participants - Part 1
Secondary ID [1] 307431 0
ONC201-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 326794 0
Solid Tumours 326795 0
Abnormal cardiac repolarization 326796 0
Condition category
Condition code
Cancer 324010 324010 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, as per the following groups:
Part 1 - 3 x Healthy Volunteers will be dosed once only with ONC201 750 mg (6 capsules)
3 x Healthy Volunteers will be dosed twice, 4 hours apart with ONC201 625mg (5 capsules)
Adherence to intervention will be via mouth check of swallowed capsule
both groups will occur simultaneously and will be run in parallel both being able to be dosed the same time
Intervention code [1] 323871 0
Treatment: Drugs
Comparator / control treatment
No comparator or control
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331802 0
Part 1: Determine the Cmax, Tmax, AUClast, AUCinf, %AUCextrap, t1/2, CL/F, Vz/F of ONC201 administered as an oral single dose of ONC201 750 mg and as 2 oral doses of ONC201 625 mg administered 4 hours apart in healthy adult participants.
Timepoint [1] 331802 0
Plasma ONC201 PK parameters: For participants receiving the single ONC201 750 mg dose, blood samples will be collected at pre-dose (within 15 minutes prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, and 48 hours post dose
For participants receiving the two single ONC201 625 mg doses administered 4 hours apart, blood samples will be collected at pre-dose (within 15 minutes prior to the first dose) 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, 6.5, 8, 10, 12, 14, 16, 24, 36, and 48 hours post dose Collection times are relative to the first dose of ONC201.
Secondary outcome [1] 411223 0
Part 1: Determine the safety, and tolerability of ONC201 administered as a single dose of ONC201 750 mg and as 2 doses of ONC201 625 mg administered 4 hours apart in healthy adult participants
Timepoint [1] 411223 0
Clinical and laboratory safety parameters including:
-adverse events (AEs) such as fatigue, headache , nausea and vomiting - continuously Screening through to Day 14 via clinical examination, participant self-reported in diary,
non absolute and changes over time of blood samples - hematology and clinical chemistry - at Screen. Day -1, Day 3 and Day 14 post dose
Vital signs (pulse, Blood pressure,temperature and respiratory rate), all measured through an integrated digital monitoring system - 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

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)
Part 1 - Allocation not concealed
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Part 1; Open label sentinel dosing. Randomized 1:1 to receive either a single oral dose of ONC 201 750 mg or two single oral doses of ONC201 625 mg administered 4 hours apart
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
In this study 6 participants will be randomized, Safety data will be analyzed descriptively using frequencies of events or continuous statistical summaries for each dosing regimen.
ONC201 plasma PK parameters will be listed and summarized by treatment.
To inform the selection of the ONC201 dose/dosing schedule for Part 2 TQT study, safety and PK data from the Part 1 lead-in study will be reviewed by dosing regimen. The safest dose/dosing regimen of ONC201 that best approximates the patient Cmax and AUC values observed in patients clinically will be taken forward into Part 2.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/08/2022
Actual
8/11/2022
Date of last participant enrolment
Anticipated
Actual
30/11/2022
Date of last data collection
Anticipated
Actual
27/12/2022
Sample size
Target
6
Accrual to date
Final
6
Recruitment outside Australia
Country [1] 24852 0
New Zealand
State/province [1] 24852 0
Christchurch

Funding & Sponsors
Funding source category [1] 311704 0
Commercial sector/Industry
Name [1] 311704 0
Chimerix, Inc.
Country [1] 311704 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] 313160 0
None
Name [1] 313160 0
Address [1] 313160 0
Country [1] 313160 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311156 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 311156 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
New Zealand
Ethics committee country [1] 311156 0
New Zealand
Date submitted for ethics approval [1] 311156 0
20/07/2022
Approval date [1] 311156 0
22/08/2022
Ethics approval number [1] 311156 0

Summary
Brief summary
The purpose of part 1 of this study is to:
• Evaluate how safe and well tolerated either a single 750mg dose or two 625mg doses of ONC201 is, in healthy participants.
• To help determine the dose level and schedule for Part 2 of the ONC201-102 study

Part 1 will enroll 6 participants to be randomized 1:1 to receive ONC201 750 mg, single dose (3 participants) or ONC201 administered as two 625 mg doses given 4 hours apart (3 participants).
Participants will be housed in the clinic on Day -1 through to Day 3.
Part 1 - will consist of a screening period of up to 28 days, in house period - Day -1 to Day 3 and a Follow up visit at Day 14 post dose.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120142 0
Dr Alex Cole
Address 120142 0
New Zealand Clinical Trials - Christchurch
264 Antigua Street
Christchurch 8140
Country 120142 0
New Zealand
Phone 120142 0
+64 3 3729477
Fax 120142 0
NA
Email 120142 0
[email protected]
Contact person for public queries
Name 120143 0
Dr Alex Cole
Address 120143 0
New Zealand Clinical Trials - Christchurch
264 Antigua Street
Christchurch 8140
Country 120143 0
New Zealand
Phone 120143 0
+64 3 3729477
Fax 120143 0
NA
Email 120143 0
[email protected]
Contact person for scientific queries
Name 120144 0
Dr Alex Cole
Address 120144 0
New Zealand Clinical Trials - Christchurch
264 Antigua Street
Christchurch 8140
Country 120144 0
New Zealand
Phone 120144 0
+64 3 3729477
Fax 120144 0
NA
Email 120144 0
[email protected]

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.