None listed
Conditions
Brief summary
This is a open-label, randomized, 3-period, 6-sequence crossover study to determine the relative bioavailability of two formulations (10% and 30%) of radiprodil under fasted and fed conditions in healthy adult participants. Radiprodil may be indicated for use in patients with GRIN related disorders, but a trial of the drug in healthy volunteers is needed before trials in patients with GRIN related disorders can proceed. Who is it for? You may be eligible for this study if you are aged 18 to 55 years and are in good general health without a clinically significant medical history. Study details: All healthy volunteer participants who choose to enrol in this study will receive a single dose of radiprodil over 3 separate periods under fasted and fed conditions. All participants will have their vital signs checked (heart rate, blood pressure, temperature, etc), and will provide blood and urine samples for testing. The data generated in this study will inform the design of future clinical studies and to select the dose(s) for future studies in patients with GRIN related disorders.
Interventions
This is an open-label, randomised, 3-period, 6-sequence crossover study to determine the relative bioavailability of two formulations (10% and 30%) of radiprodil under fasted conditions and the effect of food on the bioavailability of the 30% formulation in healthy adult participants. Approximately 18 healthy adult male and female participants will be enrolled and randomised to 1 of 6 treatment sequences in equal proportion: ABC, ACB, BAC, BCA, CAB, or CBA.
• Treatment B: Single oral dose of 45
This is an open-label, randomised, 3-period, 6-sequence crossover study to determine the relative bioavailability of two formulations (10% and 30%) of radiprodil under fasted conditions and the effect of food on the bioavailability of the 30% formulation in healthy adult participants. Approximately 18 healthy adult male and female participants will be enrolled and randomised to 1 of 6 treatment sequences in equal proportion: ABC, ACB, BAC, BCA, CAB, or CBA. • Treatment B: Single oral dose of 45 mg radiprodil (30%) under fasted conditions. Day -1 participants will fast overnight for at least 10 hours prior to the administration of radiprodil in on Day 1. Participants will continue to fast for an additional 4 hours after administration of IP. • Treatment C: Single oral dose of 45 mg radiprodil (30%) under fed conditions. Following an overnight fast of at least 10 hours, participants will eat a high fat, high calorie breakfast to be consumed prior to administration of radiprodil 30 minutes after the start of the meal and consisting of: 1. Two eggs fried in butter 2. Two rashers of bacon 3. Two slices of toast with 16 g butter per slice 4. 125 g of hash browns 5. 240 mL of full cream milk There will be at least a 96-hour washout period between doses. Adherence to and administration of study treatment will be conducted by delegated study site personnel.
Sponsors
GRIN Therapeutics, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males and females between 18 and 55 years of age, inclusive, at Screening. 2. Body mass index (BMI) between 18 and 32 kg/m2 (inclusive) and weighs at least 50 kg at Screening. 3. Healthy in the opinion of the Investigator, based upon medical history, physical examination (including 12-lead ECG, and clinical laboratory assessments without any clinically significant findings, as deemed by the Investigator) at Screening and prior to dosing on admission or pre dose as applicable. 4. Female participants must be non-lactating and of non-child-bearing potential (i.e., surgically sterilized by hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 6 weeks before Screening) or postmenopausal (defined as no menses for 12 months without an alternative medical cause and a follicle stimulating hormone [FSH] result per local laboratory guidelines; luteinizing hormone [LH] testing may be done if FSH results are inconclusive), or, if of child-bearing potential: a. Must have a negative pregnancy test at Screening and a negative pregnancy test on Day -1, prior to dose administration. b. Must agree not to donate ova or attempt to become pregnant from the time of signing consent until at least 90 days after the last dose of radiprodil. c. If not exclusively in a same-sex relationship, must agree to use adequate contraception (which is 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 radiprodil. 5. Male participants, if not surgically sterilized, must: a. Agree not to donate sperm from the time of signing consent until at least 90 days after the last dose of IP. b. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception (defined as use of a condom plus a highly effective method of contraception) from the time of signing consent until at least 90 days after the last dose of IP. c. If engaging in sexual intercourse with a female partner who is not of child-bearing potential or a same-sex partner, must agree to use a condom from the time of signing consent until at least 90 days after the last dose of IP 6. Ability to provide signed informed consent and to understand and comply with the requirements of the study including dietary requirements and requirement to stay confined on site for the duration of the study.
Exclusion criteria
1. History of hypersensitivity to radiprodil or any components of the formulations. 2. History of any medical condition that, in the opinion of the Investigator, would pose an additional risk to the participant by their participation in the study. 3. Females who are pregnant, breastfeeding, or have a positive pregnancy test at Screening or on Study Day -1. 4. History or presence of significant (in the opinion of the Investigator) cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, urologic, neurological, malignancy, psychiatric disease, or brain surgery or injury. 5. Any surgical or medical condition that, in the opinion of the Investigator, could interfere with the absorption, distribution, metabolism, or excretion of the drug. 6. History of any clinically significant allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic seasonal allergies at time of dosing on Day 1). 7. History of illicit drug abuse or alcohol abuse use within 2 years of Screening. 8. 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). 9. Routine consumption of more than 2 units of alcoholic beverages per day or more than 14 units per week (A unit of alcohol is equivalent to 1 can of beer, 1 glass of wine, or the equivalent of 1 alcoholic drink). 10. Routine consumption of an average of more than five (5) 240 mL servings of coffee or other caffeinated beverages per day. 11. A positive test result for amphetamines, barbiturates, benzodiazepines, cocaine metabolites, opiates, methylenedioxymethamphetamine, cotinine, or alcohol at Screening or Day 1. 12. Use of marijuana (including prescribed marijuana) within 30 days of Day -1. 13. Use of tobacco-containing products and nicotine or nicotine containing products in the 2 months prior to Day 1. 14. Use of any investigational product and prescription drug (with the exception of birth control medication) within 30 days of Day -1 or within 5 half lives whichever is longer. 15. Use of any over-the-counter (OTC) medication including herbal products (e.g., St John’s wort) within the 14 days or 5 half-lives prior to dosing, whichever is longer, and through the completion of all study procedures. Up to 2 grams per day of acetaminophen will be allowed at the discretion of the Investigator. 16. Any vaccine within 7 days of Day -1. 17. Donation of blood or blood products within 30 days of Day -1. 18. Acute illness within 14 days of study Day 1. 19. Positive serologic findings for HBsAg, HCV Ab, and/or HIV Ab at Screening. 20. Surgery within the past 90 days prior to Day 1 as determined by the Investigator to be clinically relevant. 21. Blood pressure was less than 90/40 mmHg or greater than 140/90 mmHg at Screening. 22. Heart rate (HR) < 40 or > 100 beats/minute after at least 5 minutes rest in supine, semi-supine, or seated position (whichever is site standard) 23. Any clinically significant ECG abnormality at Screening (as deemed by the Investigator). 24. QTcF interval > 450 msec for male and >470 msec for female (the average value for the triplicate ECG at Screening and Day -1), or history of prolonged QT syndrome. 25. Dosed in another clinical trial within 28 days prior to radiprodil dosing. 26. 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, or other products containing these fruits within 10 days prior to dosing c. Xanthine-containing products (e.g., tea, coffee) within 24 hours prior to dosing 27. Poor venous access.
Outcome results
None listed