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Trial registered on ANZCTR


Registration number
ACTRN12624001366549
Ethics application status
Approved
Date submitted
11/09/2024
Date registered
13/11/2024
Date last updated
13/11/2024
Date data sharing statement initially provided
13/11/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
An Open-label, 2 Part, Study to Assess the Pharmacokinetics of a Spray Dried Dispersion Formulation of Radiprodil Under Fasted and Fed Conditions in Healthy Adult Subjects: Part A
Scientific title
An Open-label, 2 Part, Study to Assess the Pharmacokinetics of a Spray Dried Dispersion Formulation of Radiprodil Under Fasted and Fed Conditions in Healthy Adult Subjects: Part A
Secondary ID [1] 312787 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glutamate receptor ionotropic N-methyl-D-aspartate (GRIN) related disorder - neurodevelopmental syndromes 334844 0
Condition category
Condition code
Neurological 331399 331399 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 331586 331586 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, 2 part, study to determine the pharmacokinetics of the spray dried dispersion (SDD) formulation of radiprodil under fasted and fed conditions.

The study will be conducted in 2 Parts.

Part A of the study is a single oral 15 mg dose of radiprodil SDD.

Part B is a food effect study, assessing the effect of consumption of food prior to a single oral dose of radiprodil and the effect of food after a single oral dose of radiprodil. (Note: the dose of radiprodil in Part B is not yet known)

All participants will be screened between Day-28 and Day -2.

Participants will be confined to the clinical research unit (CRU) from Day -1 to Day 5 to monitor adherence to the intervention.

This entry in the ANZCTR registry describes Part A
Intervention code [1] 329322 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339160 0
To determine the PK parameters of radiprodil and metabolites after administration of an oral single dose of radiprodil SDD formulation
Timepoint [1] 339160 0
PK sampling will be done at Day 1 pre-dose (within 60 minutes prior to dosing), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 16 hours post-dose, Day 2, 24 and 36 hours post-dose, Day 3 post-dose, Day 4 post-dose and Day 5 (End of Treatment/End of Study) post-dose.
Secondary outcome [1] 438829 0
To assess the safety and tolerability of radiprodil after oral administration of single oral dose of radiprodil SDD formulation. This will be assessed as a composite outcome.
Timepoint [1] 438829 0
Assessment of safety and tolerability will be done daily from screening until the end of treatment.

Adverse events: The severity of any adverse events experienced during the study will be categorised by the Investigator as 'Mild,' 'Moderate,' or 'Severe.' These events will be continuously monitored and assessed as soon as they are reported or observed. The review of these events will occur daily, starting from the Screening phase and continuing throughout the study, using safety assessments, observations, and reports from participants.

Vital signs: Blood pressure and heart rate is measured using sphygmomanometer respiratory rate by manual breath count, temperature by thermometer. Vital signs will be measured at screening and check in (Day -1); on Day 1 within 60 minutes prior to dosing with radiprodil SDD and at 1, 3, 4 and 6 hours (± 15 minutes) post-dose; once daily on Day 2, 3, and 4 (within 15 minutes of time of radiprodil dosing on Day 1); and on Day 5 within 15 minutes prior to the 96 hour post-dose PK blood collection. Measurement of vital signs will occur after the participant has been resting for at least 5 minutes in a semi-supine position prior to assessment. Vital signs will include temperature, respiratory rate, blood pressure, and pulse.

12-lead ECG will be recorded after the participant has been resting for at least 5 minutes in the semi-supine position. Triplicate ECGs (each replicate separated by at least 1 minute and the full set of triplicates completed within 5 minutes) are performed at Screening and on Day -1 only, all other time points will be single readings. On Day 1, ECGs will be taken within 60 minutes prior to radiprodil SDD dose and at 1, 3 and 4 hours (± 15 minutes) post-dose. On Day 5, ECGs will be taken within 15 minutes prior to the 96 hour post-dose PK blood collection. If a participant experienced a post-dose QTcF > 500 msec or > 480 msec with a concomitant change-from-baseline QTcF > 60 msec, additional ECGs are to be recorded until normalization or return to baseline. The average of the triplicate recordings of the following intervals will be reported: ventricular heart rate, RR interval; PR interval; QRS duration; QT interval; and QTcF. Assessments should include comments on whether the tracings are normal or abnormal; rhythm; presence of arrhythmia or conduction defects; morphology; any evidence of myocardial infarction; or ST-segment, T Wave, and U Wave abnormalities.

Clinical laboratory testing will occur at screening; at check-in (Day -1); on Day 2 at 24 hour (+/- 15 minutes for blood sample; +/- 3 hours for urine sample) post-dose, and on Day 5 following the 96 hour PK sample (within 15 minutes for blood sample; within 3 hours for urine sample). Participants will be requested to fast for at least 10 hours prior to each clinical laboratory blood sample collection timepoint, except in the instance of an End of Treatment visit. Blood and urine samples will be processed per the clinic’s standard processes.

Eligibility
Key inclusion criteria
1. Must have given written informed consent before any study-related activities are performed and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects.
2. Adult males and females, 18 to 55 years of age (inclusive) at screening.
3. Body mass index (BMI) more than or equal to 18.0 and less than or equal 32.0 kg/m2, with a body weight more than 50 kg at screening.
4. Medically healthy (in the opinion of the PI or delegate), as determined by pre-study medical history, and without clinically significant abnormalities including the following:
a. Physical examination without any clinically relevant findings;
b. Systolic blood pressure in the range of 90 to 140 mmHg and diastolic blood pressure in the range of 40 to 90 mmHg after resting for 5 minutes in a semi-supine position.
c. Pulse rate in the range of 40 to 100 bpm after 5 minutes resting in a semi-supine position.
d. Body temperature (tympanic), between 35.5°C and 37.5°C.
e. Electrocardiogram without clinically significant abnormalities including QT interval corrected using the Fridericia formula (QTcF) <450 msec for male participants and less than 470 msec for female participants.
f. No clinically significant findings in clinical chemistry, hematology, coagulation, and urinalysis tests.
5. Female volunteers:
a. Must be of non-child-bearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or
b. If of child-bearing potential, must:
I. Have a negative pregnancy test at the screening visit and on admission to the CRU on Day-1.
II. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 90 days after the last dose of study drug.
III. Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception from one month prior to screening until at least 90 days after the last dose of study drug, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle.
6. Male volunteers, if not surgically sterilized, must:
a. Agree not to donate sperm from signing the consent form until at least 90 days after the last dose of study drug.
b. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as use of a condom combined with use of a highly effective method of contraception) from signing the consent form until at least 90 days after the last dose of study drug.
c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom from signing the consent form until at least 90 days after the last dose of study drug.
Note – abstinence, from signing the consent form until at least 90 days after the last dose of study drug, is an acceptable form of contraception if this is in line with the male participant’s usual practice.
7. Have suitable venous access for blood sampling.
8. Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Known hypersensitivity to the study drug or any of the study drug ingredients.
2. History of suicide attempts or deliberate self-harm, or a score of 4 or 5 on ideation or any suicidal behaviour on the Columbia-Suicide Severity Rating Scale (C SSRS).
3. History of anaphylaxis or other significant allergy (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic seasonal allergies at time of dosing on Day 1) which, in the opinion of the PI (or delegate), would interfere with the volunteer’s ability to participate in the study.
4. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, psychiatric, or neurological disease/disorder, including any acute illness, determined by the PI (or delegate) to be clinically relevant.
5. History of surgery within 3 months prior to Day 1 as determined by the PI (or delegate) to be clinically relevant, or surgery planned during the study.
6. History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia.
7. Presence or having sequelae of gastrointestinal, liver (including Gilbert’s syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
8. Liver function test results elevated more than 1.5-fold above the ULN for gamma glutamyl transferase (GGT), bilirubin (total, conjugated and unconjugated), ALP, AST or ALT. Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the PI (or delegate), if the levels are unaccompanied by clinical signs and are determined to be normal variants.
9. Estimated creatinine clearance (CrCl) less than 60 mL/min using the Cockcroft-Gault formula or serum creatinine more than 1.5-fold above the ULN.
10. A history of or positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
11. Positive drugs of abuse test, cotinine test or alcohol breath test results at the screening visit and/or on admission to the CRU on Day 1.
12. Regular consumption of more than 10 standard alcoholic drinks/week and/or more than 4 standard alcoholic drinks on any one day, where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc/Vol], 100 mL wine [12% Alc/Vol], or 30 mL spirit [40% Alc/Vol]).
13. Routine consumption of an average of more than five (5) 240 mL servings of coffee or other caffeinated beverages per day.
14. Use of marijuana (including prescribed marijuana) within 30 days of Day -1.
15. Use of tobacco-containing products and nicotine or nicotine containing products in the 2 months prior to Day 1.
16. Females who are breastfeeding or planning to breastfeed.
17. Unable to swallow oral medication.
18. Use of any prescription or over-the-counter medication (including herbal products, diet aids, vitamins, and hormone supplements) within 14 days or 5 half-lives of the medication (whichever is longer) prior to the first dose of study drug, except use of contraceptives. Up to 2 grams per day of acetaminophen will be allowed at the discretion of the Investigator.
19. Acute illness within 14 days of study Day 1.
20. Use of any vaccinations within 7 days prior to screening.
21. Donation of blood or plasma within 30 days prior to first dose of study drug, or loss of whole blood of more than 500 mL within 30 days prior to first dose of study drug, or receipt of a blood transfusion within 1 year of the first dose of study drug.
22. Dosed in another clinical trial within 28 days prior to radiprodil dosing. Participants enrolled in Part A of the RAD-GRIN-503 study are permitted to participate in Part B if there is at least 7 days between the last dose administered in Part A and the first dose administration in Part B.
23. Consumption of the following prior to dosing period:
a. Alcohol 48 hours prior to dosing.
b. Grapefruit (or pomelo or star fruit), Seville oranges, Seville orange marmalade, poppy seeds or other products containing these fruits within 10 days prior to dosing.
c. Caffeine and/or xanthine-containing products (e.g., tea, coffee) within 24 hours prior to dosing.
24. Any other condition or prior therapy that in the opinion of the PI (or delegate) would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

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
Not yet recruiting
Date of first participant enrolment
Anticipated
18/11/2024
Actual
Date of last participant enrolment
Anticipated
8/12/2024
Actual
Date of last data collection
Anticipated
12/02/2025
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 317219 0
Commercial sector/Industry
Name [1] 317219 0
GRIN Therapeutics, Inc.
Country [1] 317219 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
GRIN Therapeutics, Inc.
Address
Country
United States of America
Secondary sponsor category [1] 319507 0
Commercial sector/Industry
Name [1] 319507 0
Avance Clinical Pty Ltd
Address [1] 319507 0
Country [1] 319507 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315954 0
Bellberry Human Research Ethics Committee D
Ethics committee address [1] 315954 0
https://bellberry.com.au/
Ethics committee country [1] 315954 0
Australia
Date submitted for ethics approval [1] 315954 0
11/10/2024
Approval date [1] 315954 0
18/10/2024
Ethics approval number [1] 315954 0

Summary
Brief summary
This study is testing the safety, tolerability (if any side effects occur), pharmacokinetics (PK; the amount of experimental drug or any breakdown products in the blood), of a single dose/food effect of an experimental drug called Radiprodil in the presence or absence of food (food effect).

This entry in the ANZCTR registry describes Part A: a single oral 15 mg dose of radiprodil SDD.

Radiprodil is being developed as a potential new treatment of tuberous sclerosis complex (a rare genetic disease that causes non-cancerous tumours to grow in the brain and several other areas of the body) and focal cortical dysplasia (a malformation of neurons in a region of the brain called the cortex). Radiprodil is expected to reduce the risks of seizures and negative developmental outcomes that are characteristic in patients with these conditions. In patients with these disorders nearly all will have a form of epilepsy (seizures) from a very young age that does not respond to current treatments available. Seizures can affect the process of normal development and cognitive skills leading to behavioural issues and negative developmental outcomes. Radiprodil has the potential to normalise the pathways in the brain that are involved in seizures and therefore reduce the risks of seizures, negative developmental outcomes and other significant symptoms that are characteristic in patients with these conditions.

The purpose of this study is to test the safety and tolerability of a new version of oral radiprodil called Sprayed Dried Dispersion (SDD) radioprodil when taken as a single dose either with or without food. The study will also assess the plasma pharmacokinetic profile (how a drug moves through the bloodstream over time) of the SDD radiprodil.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 136334 0
Dr Ofer Gonen
Address 136334 0
Nucleus Network, Level 5, Burnet Tower, 89 Commercial Rd, Melbourne, Victoria, 3004
Country 136334 0
Australia
Phone 136334 0
+61 03 8593 9801
Fax 136334 0
Email 136334 0
[email protected]
Contact person for public queries
Name 136335 0
Tristan Iseli
Address 136335 0
Avance Clinical, 213 Glynburn Road, Firle, South Australia, 5070
Country 136335 0
Australia
Phone 136335 0
+61 08 8249 94788
Fax 136335 0
Email 136335 0
[email protected]
Contact person for scientific queries
Name 136336 0
Tristan Iseli
Address 136336 0
Avance Clinical, 213 Glynburn Road, Firle, South Australia, 5070
Country 136336 0
Australia
Phone 136336 0
+61 08 8249 94788
Fax 136336 0
Email 136336 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.