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Trial registered on ANZCTR


Registration number
ACTRN12621001003864
Ethics application status
Approved
Date submitted
13/07/2021
Date registered
30/07/2021
Date last updated
30/07/2021
Date data sharing statement initially provided
30/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the safety and tolerability of ONC201 in healthy adults under fasting and fed conditions - Part 2b
Scientific title
A Phase 1, randomized study to evaluate the safety, tolerability, and pharmacokinetics (PK) of the effects of food on the bioavailability of ONC201 following oral administration in healthy adult subjects - Part 2b
Secondary ID [1] 304765 0
ONC201-101 Part 2b
Universal Trial Number (UTN)
Trial acronym
Linked study record
This record is one part out of three parts of the ONC201-101 study, Part B1 is registered as ACTRN12621000975897.

Health condition
Health condition(s) or problem(s) studied:
Cancer 322814 0
Condition category
Condition code
Cancer 320402 320402 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will randomly receive each of the following single-dose treatments over the course of 2 treatment periods with a washout interval between doses of at least 7 days:
• Treatment A: Single 625 mg dose of ONC201 administered as five 125 mg capsules under a fasting condition (nothing but water for at least 10 hours).
• Treatment B: Single 625 mg dose of ONC201 administered as five 125 mg capsules within 10 mins after consumption (in entirety) of a standardized high-fat meal (800-1000 total calories).
All single doses will be administered in the clinic and a mouth check to confirm compliance will occur.
Allocation to sequence of treatment periods will occur based on a randomisation list.
The standardized meal is a high fat content breakfast that has approximately 50% of calories from fat and is a total of approximately 800-1000 calories (fat and non-fat).
Intervention code [1] 321145 0
Treatment: Drugs
Comparator / control treatment
Treatment A: fasting condition - Single 625 mg dose of ONC201 given orally. A mouth check to confirm compliance will occur.
Control group
Active

Outcomes
Primary outcome [1] 328237 0
To investigate the safety and tolerability ( by review of clinical and laboratory safety parameters including: AEs, absolute and changes over time of hematology, clinical chemistry, vital signs, and ECG intervals) following single doses of ONC201 administered orally in healthy adults in all parts of the study
Adverse events: assessed in accordance with the Common Terminology Criteria for Adverse Events (CTCAE5.0)
heart rate assessed using radial pulse
haematology/Biochemistry assessed using a blood sample
ECG parameters (PR, QRS, QT, and QTc intervals) assessed by review of ECG print out.
Neurological (Neurological Assessment in Neuro-Oncology (NANO) scale) and physical examinations assessed for changes.
Timepoint [1] 328237 0
laboratory safety parameters taken on screening, on Days -1, 3, and 7 post dose in each treatment period, and at the Follow Up (FU) - 14 days after last dose/Withdrawal (WD) visit
Adverse events (AEs) reviewed continually throughout the trial,
Vital signs - (blood pressure, respiratory rate, pulse rate, and temperature) will be measured at screening, on Days -1, 1, and 3 post dose in each treatment period, and at the FU - 14 days after last dose/WD visit, On Day 1 in each treatment period, measurements will be taken predose (3 replicates at 1-minute intervals, performed 1 hour prior to dosing) and at approximately 3 hours post dose.
ECG- will be performed at screening, on Day 1 and 3 post dose in each treatment period, and at the FU - 14 days after last dose/WD visit. On Day 1, ECGs will be obtained predose and at approximately 2, 4, 8, and 24 hours post dose
Secondary outcome [1] 398226 0
To characterize plasma ONC201 Cmax, Tmax, AUClast, AUCinf, %AUCextrap, t1/2, CL/F, Vz/F following single escalating doses of ONC201 administered orally in healthy adults
Timepoint [1] 398226 0
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, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, and 168 hours post dose.

Eligibility
Key inclusion criteria
1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions in this protocol.
2. Male or female between 18 to 55 years of age.
3. Female must be of non-childbearing potential i.e., postmenopausal woman or a premenopausal woman documented as surgically sterile following either a hysterectomy and/or bilateral oophorectomy, tubal ligation or placement of bilateral fallopian tube occlusion, or with medically documented ovarian failure.
4. Males must be surgically sterilized OR must agree to use an acceptable method(s) of contraception during heterosexual intercourse with a female partner capable of becoming pregnant while enrolled in the study
5. Males must agree to refrain from sperm donation during the study and for at least 90 days after study drug administration.
6. Body mass index from 18 to 32 kg/m2, inclusive.
7. Participants who are overtly healthy as determined by medical evaluation and judgment of the investigator including medical history, Physical Exam, laboratory tests, vital signs, and cardiac monitoring.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1.If male, have a female partner who is pregnant or planning to become pregnant during the study or within 90 days after study drug administration.
2.Have received any investigational drug, agent, or device within 30 days prior to Day 1, or current participation in another investigational study.
3. Have a positive result for Hepatitis B/C or HIV.
4. Have a positive test for drugs of abuse, cotinine, and/or alcohol
5. Current history of heavy tobacco/nicotine use.
6. Any serious or active medical or psychiatric illness, which could interfere with participant treatment, assessment, or compliance with the protocol.
7. Have a history of a gastrointestinal condition that could interfere with the absorption of the study drug
8. Have a history or symptoms of cardiovascular disease, including but not limited to coronary artery disease, hypertension, congestive heart disease.
9. Have a history of hematological disorders, including disorders such as a bleeding disorder or a risk of gastrointestinal bleeding.
10. Have a history of chronic liver disease or hepatic impairment,
11. Total bilirubin greater than the upper limit of the normal reference range at screening or on Period 1 Day -1.
12. Have symptoms of acute infection within 2 weeks prior to Period 1 Day 1.
13. Have clinically significant abnormal hemoglobin as determined by the investigator at the screening evaluation
14. Have donated a unit of blood or had clinically significant blood loss within 30 days prior to Period 1 Day 1 or donated plasma within 7 days prior to Period 1 Day 1.
15. Have received any prescription medication, vaccines, or any nonprescription medication (including vitamins and herbal products) within 14 days prior to Period 1 Day 1

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)
Allocation is 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 (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis
PK parameters following single-dose administration will be determined using standard noncompartmental methods and actual sampling times utilizing a PK data analysis program (e.g., Phoenix WinNonlin or equivalent).
Safety will be assessed through AEs, measurement of vital signs, ECGs, neurological assessments, and clinical laboratory test results. All AEs reported and any concomitant medication intake will also be documented.
Plasma ONC201 and ONC207 (metabolite) concentrations will be listed and summarized by treatment and timepoint. Individual and mean plasma concentration-time profiles will be plotted. Plasma ONC201 and ONC207 PK parameters will be listed and summarized by treatment.
The primary endpoints for assessment of bioavailability will be AUC and Cmax of ONC201. If AUCinf is not well estimated, AUClast will be used for assessment of bioavailability. Ninety percent (90%) CIs for the ratio of the geometric means of each of these parameters will be determined using mixed effects models. The CIs will be compared with the bioequivalence limits of 80% to 125% in order to examine the effect of food on the bioavailability of ONC201.



Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 23958 0
New Zealand
State/province [1] 23958 0
Christchurch

Funding & Sponsors
Funding source category [1] 309136 0
Commercial sector/Industry
Name [1] 309136 0
Chimerix, Inc.
Address [1] 309136 0
2505 Meridian Parkway, Suite 100, Durham, NC USA 27713
Country [1] 309136 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] 310090 0
None
Name [1] 310090 0
Address [1] 310090 0
Country [1] 310090 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309003 0
Central Health & Disability Ethics Committee
Ethics committee address [1] 309003 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
New Zealand
Ethics committee country [1] 309003 0
New Zealand
Date submitted for ethics approval [1] 309003 0
14/06/2021
Approval date [1] 309003 0
06/07/2021
Ethics approval number [1] 309003 0
21/CEN/158

Summary
Brief summary
ONC201 is an investigational drug being developed to treat high grade glioma (a type of brain cancer). “Investigational” means that the FDA (the U.S. Food and Drug Administration) has not approved ONC201 as a treatment for this condition. ONC201 is a newly discovered compound that may stop cancer cells from growing. This drug has been shown in laboratory experiments to use a new way to kill brain tumor cells but not normal cells.
The study sponsors need to know how the drug works in healthy adults to compare this with when the drug is taken in cancer patients.
Part B2 will review the effect of food on a single dose of ONC201. Participants will receive 2 doses of ONC201 - with and without a high fat meal. It is envisaged that 30 participants will be recruited in Part B2.
Please see linked studies.
In each treatment period, ONC201 will be administered on Day 1. Participants will be admitted to the clinic on the day prior to dosing, and remain in the clinic until discharged on the morning of Day 3 following completion of all scheduled study procedures and assessments.

Safety will be assessed through the reporting of AEs, vital signs measurements, Neurological and Physical examinations, ECGs and clinical laboratory results.

Please see linked studies, part 1 (ACTRN12621000975897).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112618 0
Dr Chris Wynne
Address 112618 0
New Zealand Clinical Trials - Christchurch
264 Antigua Street
Christchurch 8140
Country 112618 0
New Zealand
Phone 112618 0
+64 3 3729477
Fax 112618 0
NA
Email 112618 0
chris.wynne@nzcr.co.nz
Contact person for public queries
Name 112619 0
Dr Chris Wynne
Address 112619 0
New Zealand Clinical Trials - Christchurch
264 Antigua Street
Christchurch 8140
Country 112619 0
New Zealand
Phone 112619 0
+64 3 3729477
Fax 112619 0
NA
Email 112619 0
chris.wynne@nzcr.co.nz
Contact person for scientific queries
Name 112620 0
Dr Chris Wynne
Address 112620 0
New Zealand Clinical Trials - Christchurch
264 Antigua Street
Christchurch 8140
Country 112620 0
New Zealand
Phone 112620 0
+64 3 3729477
Fax 112620 0
NA
Email 112620 0
chris.wynne@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 other documents available
Summary results
No Results