Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001072505p
Ethics application status
Submitted, not yet approved
Date submitted
22/08/2024
Date registered
5/09/2024
Date last updated
5/09/2024
Date data sharing statement initially provided
5/09/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 Drug-Drug Interaction Study to Assess the Interaction Potential of NB-4746 on CYP1A2 and CYP3A4 Substrates in Healthy Volunteers
Scientific title
A Phase 1 Drug-Drug Interaction Study to Assess the Interaction Potential of NB-4746 on CYP1A2 and CYP3A4 Substrates in Healthy Volunteers
Secondary ID [1] 312572 0
CL-4746-24-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic lateral sclerosis 334493 0
Condition category
Condition code
Neurological 331107 331107 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant will receive
• Caffeine - 1 x 100mg tablet taken orally on Day 1 and Day 9
• Midazolam - 1mg (mixed with apple juice) taken orally on Day 1 and Day 9.
• NB-4746 - 100mg (mixed with water and flavoured syrup) taken orally, twice a day on Day 3 to Day 9 and in the morning of Day 10.
Participants are administered all study medications by the site staff at the site.
Intervention code [1] 329092 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 338870 0
To evaluate potential drug-drug interactions of NB-4746 with CYP1A2 (caffeine) and CYP3A4 (midazolam) substrates in healthy volunteers.
Timepoint [1] 338870 0
Plasma PK collections for CYP1A2 (caffeine/paraxanthine)/CYP3A4 (midazolam) substrate analysis will be performed at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, and 48 hours after Day 1 and Day 9 dosing.
Secondary outcome [1] 437734 0
1. To evaluate the safety and tolerability of NB-4746 dosing 100 mg twice a day (BID) for 8 days in healthy volunteers
Timepoint [1] 437734 0
Daily from Day 1 to Day 14 as well as at the End of Study/End of Treatment visit.
Secondary outcome [2] 437735 0
To evaluate the Pharmacokinetic (PK) of NB-4746 dosing 100 mg BID for 8 days in healthy volunteers
Timepoint [2] 437735 0
PK collections for NB-4746 will be performed on Day 3 at pre-AM dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-AM dose; pre-AM dose on Days 5, 7 and 9; and on Day 10 at pre-AM dose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 32, 48, 56, 72, 80, and 96 hours post-AM dose.

Eligibility
Key inclusion criteria
Participants will be eligible to be included in the study if all of the following criteria apply:
1. Aged greater or equal to 18 years and less than or equal to 65 years.
2. Body mass index (BMI) within the range 18 to 30 kg per m2 (inclusive).
3. Overtly healthy, as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (ECG) obtained at screening and Day 1.
4. Baseline (screening and Day -1) laboratory test values within normal ranges. Out of normal range values may be accepted by the Investigator, if not clinically significant, with the exception of the following:
a. Alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than 1.5 x upper limit of normal.
b. Total, indirect, or direct bilirubin greater than 1.5 x upper limit of normal. Participants with Gilbert’s syndrome with indirect bilirubin outside of the normal range will be excluded from the study.
c. Creatinine clearance less than 80 mL per min (estimated from Cockcroft Gault equation).
d. Amylase and lipase must be within the normal range at screening and Day -1.
5. Nonsmoker and or ex-smoker who has discontinued smoking and or use of nicotine-containing products (including nicotine and non-nicotine vapes) for at least 3 months prior to the first dose of study drug, confirmed by a negative carbon monoxide (CO) breath test at screening and Day -1.
6. Willing to refrain from consumption of caffeine-containing products including, but not limited to, coffee, tea, cola drinks, and chocolate for at least 48 hours prior to the first dose of study drug through to discharge on Day 14.
7. Females must be either amenorrheic for greater than or equal to 1 year or with FSH greater than 40 mIU/mL at screening if amenorrheic less than 1 year); or surgically sterile (having undergone bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 6 months. However, to protect against the transfer of the study drug in any bodily fluids, male partners of female participants (whether postmenopausal or surgically sterile) must use a barrier form (e.g., condom) of contraception until the EOS visit or 7 days after the last dose of study drug in case of early study termination.
8. Males with female partners of childbearing potential must agree to use barrier contraceptive (i.e., condom) and their female partners must use a highly effective method of contraception from screening to 90 days after the last dose of study drug. Males must also refrain from sperm donations during this time period. Males who are abstinent will not be required to use a contraceptive method unless they become sexually active. Males in a same sex relationship must also use a barrier form of contraception against the transfer of the study drug in any bodily fluids until the End of Study visit or 7 days after the last dose of study drug in case of early termination.
9. Capable of giving signed informed consent.
10. Ability to communicate well with the Investigator, in the local language, and to understand and comply with the requirements of the study.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants are excluded from the study if any of the following criteria apply:
1. History or presence of significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drugs; or interfering with the interpretation of data.
2. History of pancreatitis or with prior cholecystectomy.
3. Any history of significant medical illness or any chronic medical illness, as determined by the investigator.
4. Mentally or legally incapacitated, has significant emotional problems at screening or expected during the conduct of the study, or has a history of a clinically significant psychiatric disorder within the last 5 years. Note: normal healthy volunteers who have had situational depression may be enrolled in the study at the discretion of the Investigator.
5. History of severe drug allergy or hypersensitivity or food allergy, including anaphylaxis.
6. Has had surgery or trauma with significant blood loss within the last 3 months prior to the first dose of study drug.
7. Has donated more than 1 unit (500 mL) of blood within 4 weeks prior to the first dose of study drug.
8. Fever (body temperature greater than 38°C) or symptomatic viral or bacterial infection within 2 weeks prior to screening.
9. Abnormal heart rate or blood pressure (mean resting heart rate less than or equal to 40 or greater than or equal to 100 bpm, systolic BP less than or equal to 90 or greter than or equal to 149 mmHg, diastolic BP less than or equal to 50 to greater than or equal to 90 mmHg) at screening or before the first administration of study drug. Vitals may be repeated up to 2 times for the purpose of eligibility.
10. Any other abnormal vital signs that are considered to be clinically significant by the investigator.
11. Lifetime history of cancer except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. Fully resected basal cell carcinoma and squamous cell carcinoma with no evidence of recurrence for 1 year are permitted.
12. QTcF interval (QT with Fridericia’s correction) greater than 450 msec in males and greater than 470 msec in females at screening, or any other ECG finding that is considered to be clinically significant by the investigator.
13. Inability to swallow or tolerate oral medications.
14. Past or intended use of over-the-counter or prescription medication (including herbal medications) within 14 days before Day 1, with the exception of occasional paracetamol (doses up to 2 g per day for no more than 3 consecutive days).
15. Live vaccine(s) within 1 month before screening or plans to receive such vaccines during the study.
16. Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) before Day 1.
17. Current participation in any other investigational drug study or receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) before Day 1.
18. Regular use of known drugs of abuse or a history of drug abuse within 12 months prior to screening or positive screening or Day -1 drugs of abuse test.
19. Regular alcohol consumption within 6 months before the study, current evidence of substance dependence or self-reported alcoholic intake >2 drinks/day for female participants and >3 drinks/day for male participants, or positive screening or Day -1 alcohol breath test. Participants must be willing refrain from consumption of alcohol for 48 hours prior to Day 1 dosing through End of Study or Early Termination visits..
20. Positive human immunodeficiency virus (HIV) or hepatitis C antibody test (HCV), or hepatitis B surface antigen (HBsAg) at screening or 3 months before Day 1.
21. Known sensitivity to the NB-4746 study drug or any of the formulation components.
22. Known hypersensitivity to midazolam or any of the formulation components, or history of acute narrow angle glaucoma. Participants with open-angle glaucoma must have well controlled disease.
23. Known hypersensitivity to caffeine or any of the formulation components.

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
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
24/09/2024
Actual
Date of last participant enrolment
Anticipated
1/11/2024
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 317004 0
Commercial sector/Industry
Name [1] 317004 0
Nura Bio Inc
Country [1] 317004 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Nura Bio
Address
Country
United States of America
Secondary sponsor category [1] 319248 0
Commercial sector/Industry
Name [1] 319248 0
Inclin Pty Ltd
Address [1] 319248 0
Country [1] 319248 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 315762 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 315762 0
Ethics committee country [1] 315762 0
Australia
Date submitted for ethics approval [1] 315762 0
24/07/2024
Approval date [1] 315762 0
Ethics approval number [1] 315762 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135710 0
Dr Christopher Argent
Address 135710 0
Scientia Clinical Research Ltd The Bright Building, Levels 5 & 6, Corner High & Avoca Streets, Randwick NSW 2031
Country 135710 0
Australia
Phone 135710 0
+61 02 9382 5800
Fax 135710 0
Email 135710 0
[email protected]
Contact person for public queries
Name 135711 0
Christopher Argent
Address 135711 0
Scientia Clinical Research Ltd The Bright Building, Levels 5 & 6, Corner High & Avoca Streets, Randwick NSW 2031
Country 135711 0
Australia
Phone 135711 0
+61 02 9382 5800
Fax 135711 0
Email 135711 0
[email protected]
Contact person for scientific queries
Name 135712 0
Christopher Argent
Address 135712 0
Scientia Clinical Research Ltd The Bright Building, Levels 5 & 6, Corner High & Avoca Streets, Randwick NSW 2031
Country 135712 0
Australia
Phone 135712 0
+61 02 9382 5800
Fax 135712 0
Email 135712 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.