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Trial registered on ANZCTR


Registration number
ACTRN12624000718549
Ethics application status
Approved
Date submitted
14/05/2024
Date registered
11/06/2024
Date last updated
4/08/2024
Date data sharing statement initially provided
11/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Three-Part Open-Label Drug-Drug Interaction Study in Healthy participants to Determine the Effects of Itraconazole on the Pharmacokinetics of JNT-517 (Victim) and the Effects of JNT-517 (Perpetrator) on the Pharmacokinetics of Midazolam and Pravastatin
Scientific title
A Phase 1, Three-Part Open-Label Drug-Drug Interaction Study in Healthy participants to Determine the Effects of Itraconazole on the Pharmacokinetics of JNT-517 (Victim) and the Effects of JNT-517 (Perpetrator) on the Pharmacokinetics of Midazolam and Pravastatin
Secondary ID [1] 312128 0
n/a
Universal Trial Number (UTN)
U1111-1308-0188
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Phenylketonuria 333797 0
Condition category
Condition code
Metabolic and Endocrine 330469 330469 0 0
Metabolic disorders
Human Genetics and Inherited Disorders 330560 330560 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 1, open-label, 3-part study to evaluate the drug-drug interaction of itraconazole with JNT-517 as the victim and the interaction of JNT-517 as the perpetrator with midazolam and pravastatin, respectively. The 3 parts of the study may be conducted in parallel and no particular order.

Part A - Itraconazole interaction:
Day 4 to Day 9 - Twice a day 150 mg oral dose of itraconazole tablets will be administered. Day 10 - Single 200 mg oral dose of itraconazole capsules will be administered.
Day 1, Day 4 and Day 10 - Single 150 mg oral dose of JNT-517 tablets will be administered.

Part B - Midazolam interaction:
Day 1 and Day 16 - Single 2 mg oral dose of midazolam solution will be administered.
Day 3 to Day 15 - Twice a day 150 mg oral dose of JNT-517 tablets will be administered. Day 16 - Single 150 mg oral dose of JNT-517 tablets will be administered.

Part C - Pravastatin interaction:
Day 1 - Single oral dose of pravastatin 40 mg tablet will be administered. Day 5 - Single oral dose of pravastatin 40 mg tablet will be administered.
Day 4 - Single 150 mg oral dose of JNT-517 tablets will be administered, Day 5 - Twice a day 150 mg oral dose of JNT-517 tablets will be administered.

Part A will begin with a sentinel group of 2 participants who will receive JNT-517 alone on Day 1 and in combination with Itraconazole on Day 4 before the rest of the participants are dosed with the study medications. In the absence of any safety findings in the sentinel group within 48 hours after the combination dosing of JNT-517 and itraconazole on Day 4, the rest of the cohort of participants may begin dosing with JNT-517. Dosing in Parts B and C may commence anytime after the 2 sentinel participants in Part A.

Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under direct supervision of the clinical research unit staff. This ensures compliance to study drug intake by participants.

A healthy volunteer can only participant in one of the 3 parts of the study,
Intervention code [1] 328585 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 338239 0
Part A - Itraconazole interaction: This part will evaluate the effect of itraconazole on the pharmacokinetics (PK) of JNT-517 in healthy participants.
Timepoint [1] 338239 0
Part A - Itraconazole interaction: Participants will be assessed daily from first dose of JNT-517 on Day 1 until Day 13 post-dose (pre-dose and at 72 hours post-dose on dosing days) and will be asked to return for a safety follow-up approximately 1 week after the final dose of study medication.
Primary outcome [2] 338317 0
Part B - Midazolam interaction: This part will evaluate the effect of JNT-517 on the single dose pharmacokinetics (PK) of midazolam in healthy participants.
Timepoint [2] 338317 0
Part B - Midazolam interaction: Participants will be assessed daily from first dose of midazolam on Day 1 until Day 18 post-dose (pre-dose and at 48 hours post-dose on dosing days) and will be asked to return for a safety follow-up approximately 1 week after the final dose of study medication.
Primary outcome [3] 338318 0
Part C - Pravastatin Interaction: This part will evaluate the effect of JNT-517 on the single dose pharmacokinetics (PK) of pravastatin in healthy participants.
Timepoint [3] 338318 0
Part C - Pravastatin Interaction: Participants will be assessed daily from first dose of pravastatin on Day 1 until Day 6 post-dose (pre-dose and at 24 hours post-dose on dosing days) and will be asked to return for a safety follow-up approximately 1 week after the final dose of study medication.
Secondary outcome [1] 435101 0
Part A - Itraconazole interaction: To evaluate safety and tolerability of JNT-517 in the presence and absence of itraconazole.
Timepoint [1] 435101 0
Part A - Itraconazole interaction: Participants will be assessed daily from first dose of JNT-517 on Day 1 until Day 13 post-dose. Participants will be discharged on Day 13 and will be asked to return for a safety follow-up approximately 1 week after the final dose of study medication.
Secondary outcome [2] 435422 0
Part B - Midazolam interaction: To evaluate safety and tolerability of JNT-517 in the presence and absence of midazolam.
Timepoint [2] 435422 0
Part B - Midazolam interaction: Participants will be assessed daily from first dose of midazolam on Day 1 until Day 18 post-dose. Participants will be discharged on Day 18 and will be asked to return for a safety follow-up approximately 1 week after the final dose of study medication.
Secondary outcome [3] 435423 0
Part C - Pravastatin interaction: To evaluate safety and tolerability of JNT-517 in the presence and absence of itraconazole, midazolam, and pravastatin, respectively.
Timepoint [3] 435423 0
Part C - Pravastatin Interaction: Participants will be assessed daily from first dose of pravastatin on Day 1 until Day 6 post-dose. Participants will be discharged on Day 6 and will be asked to return for a safety follow-up approximately 1 week after the final dose of study medication.

Eligibility
Key inclusion criteria
1. Males and females 18 to 55 years of age, inclusive.
2. Medically healthy with no clinically significant medical history, physical examination, laboratory results, vital signs, or ECGs.
3. Body mass index (BMI) of 18-40 kg/m2 and total body weight >50 kg (110 lbs).
4. Non-smoker for at least 2 weeks prior to dosing and willing to abstain during the study.
5. Participants with psychiatric illness must be well-controlled for the last 6 months prior to the Screening visit and if on medication, on stable medications for the last 3 months.
6. Capable of giving signed informed consent and able to comply with study procedures
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any acute or chronic medical condition that would prevent the participant from complying with
the procedures or place the participant at risk if they participate in the study.
2. Positive for hepatitis B or C or human immunodeficiency virus.
3. Any history of malignancy in the last 5 years, excluding non-melanoma skin cancer.
4. Any history of liver disease
Any surgical or medical conditions that may affect study drug absorption, distribution,
metabolism, or excretion.
6. Creatinine clearance <90 mL/min by the Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI) creatine equation.
7. Received another investigational drug within 30 days or, if known, 5 half-lives of the
investigational drug (whichever is longer).
8. Alcohol consumption within 5 days of Check in and/or unwilling to abstain during the study.
9. Has consumed herbal preparations/medications, including but not limited to St. John's wort, kava,
ephedra (ma huang), gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto, or ginseng,
within 7 days prior to study drug dosing.
10. Intake of nutritional supplements, juice, other foods or beverages that may affect the various drug
metabolizing enzymes and transporters (eg, alcohol, grapefruit, starfruit, Seville oranges, or their
products) are not permitted for 7 days before dosing and throughout the study.
11. Smoker (defined as an individual who has used nicotine-containing products, including cigarettes
and e-cigarettes) within the last 2 weeks prior to dosing and a positive cotinine test on Day –1.
12. Consumption of caffeinated beverages or food within 72 hours prior to Check-in.
13. Use or intend to use any prescription medications/products within 14 days prior to dosing, unless
deemed acceptable by the Investigator (or designee), or use or intend to use any nonprescription
medications/products including vitamins and minerals within 7 days prior to Check in, unless
deemed acceptable by the Investigator (or designee).
14. Use or intend to use slow release medications/products considered to still be active within 14
days prior to Check in, unless deemed acceptable by the Investigator (or designee).
15. Use of any medications that are inhibitors or inducers of cytochrome P450 (CYP)3A4 or
inhibitors of the transporter P-glycoprotein (P-gp) within 4 weeks prior to randomization and
unwilling and/or unable to avoid these medications throughout the treatment duration.
16. Use of any medication that is a substrate of CYP3A4, or a substrate of the transporters P-gp,
breast cancer resistance protein (BCRP), organic anion transporter 3 (OAT3), multidrug and toxin
extrusion (MATE)1, or MATE2-K within 4 weeks prior to randomization and unwilling and/or
unable to avoid these medications throughout the treatment duration.
17. History of drug/alcohol abuse in the last year.
18. Positive drug screen.
19. Unable to tolerate oral medication.
20. Allergy to JNT-517 or any component of the investigational product.
21. Allergy to itraconazole (Part A), midazolam (Part B), or pravastatin (Part C)
22. Previous exposure to JNT-517 in another clinical trial
23. Received >50 mL of blood or plasma within 30 days of Screening or >500 mL of blood or plasma
within 60 days of Screening.
24. Blood donation of >500 mL within 56 days prior to Screening

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
12/06/2024
Actual
11/06/2024
Date of last participant enrolment
Anticipated
Actual
27/06/2024
Date of last data collection
Anticipated
Actual
18/07/2024
Sample size
Target
36
Accrual to date
Final
36
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 316485 0
Commercial sector/Industry
Name [1] 316485 0
Jnana Therapeutics, Inc.
Country [1] 316485 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
CTI Clinical Trial and Consulting Services Australia Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 318662 0
None
Name [1] 318662 0
Address [1] 318662 0
Country [1] 318662 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315283 0
Bellberry Human Research Ethics Committee E
Ethics committee address [1] 315283 0
https://bellberry.com.au/
Ethics committee country [1] 315283 0
Australia
Date submitted for ethics approval [1] 315283 0
27/03/2024
Approval date [1] 315283 0
10/05/2024
Ethics approval number [1] 315283 0

Summary
Brief summary
This study is designed as a 3-part study in healthy participants to test the drug-to –drug interaction of experimental drug, JNT-517 with itraconazole, midazolam and pravastatin, respectively.

JNT-517 is believed to reduce levels of phenylalanine in the by increasing its removal with urine and reducing uptake of phenylalanine in the gut.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 134214 0
Dr Ofer Gonen
Address 134214 0
Nucleus Network Pty Ltd, Level 5, Burnet Tower, , 89 Commercial Road, Melbourne VIC 3004
Country 134214 0
Australia
Phone 134214 0
+61 03 85939801
Fax 134214 0
Email 134214 0
[email protected]
Contact person for public queries
Name 134215 0
Dr Ofer Gonen
Address 134215 0
Nucleus Network Pty Ltd, Level 5, Burnet Tower, , 89 Commercial Road, Melbourne VIC 3004
Country 134215 0
Australia
Phone 134215 0
+61 03 85939801
Fax 134215 0
Email 134215 0
[email protected]
Contact person for scientific queries
Name 134216 0
Mr Toby Vaughn
Address 134216 0
Jnana Therapeutics, Inc., 6 Tide Street, Suite 301, Boston MA 02210, USA.
Country 134216 0
Australia
Phone 134216 0
+1 513 5050770
Fax 134216 0
Email 134216 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
Individual results obtained are for study purposes and has no remit in clinical care of the patients. Summary results will however be made available via ANZCTR website.


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.