None listed
Conditions
Brief summary
This phase 1 study is a randomized, placebo-controlled, double-blind, trial of an oral drug called GT 02287 vs. placebo in healthy volunteers. The study will assess the safety, tolerability, Pharmacokinetics, and Food Effect in single and multiple ascending dose cohorts.
Interventions
This is a single centre, randomized, double-blind, placebo-controlled study of single and multiple ascending doses of GT-02287 in healthy volunteers.
This study will consist of 2 parts: single and multiple ascending doses of GT-02287. Participants will provide informed consent and undergo screening for the study no more than 28 days prior to Day 1. Eligible participants will check in to the clinical research unit (CRU) on Day -1, the day prior to dosing. All participants in both parts will atte
This is a single centre, randomized, double-blind, placebo-controlled study of single and multiple ascending doses of GT-02287 in healthy volunteers. This study will consist of 2 parts: single and multiple ascending doses of GT-02287. Participants will provide informed consent and undergo screening for the study no more than 28 days prior to Day 1. Eligible participants will check in to the clinical research unit (CRU) on Day -1, the day prior to dosing. All participants in both parts will attend a Follow-up Visit scheduled 7-10 days after their last dose of IP, or after early termination. - Part 1 (single ascending doses; SAD): Study participants will be randomly assigned to receive a single dose of GT-02287 or placebo administered as an oral solution on day 1. There will be 5 ascending dose cohorts in this part with 8 participants per cohort. Sentinel dosing will occur within each cohort. The first 2 participants assigned to each cohort will be randomized 1:1 to GT02287 or placebo. The remaining 6 participants in each cohort will be randomized 5:1 to GT02287 or placebo, for an overall 3:1 randomization ratio for each cohort, including cohort 4. - Cohort 1: 2.4 mg/kg - Cohort 2: 4.8 mg/kg - Cohort 3: 7.7 mg/kg - Cohort 4: 10 mg/kg, then another 10 mg/kg after at a 1-to-2-week washout (FE) - Cohort 5: 12 mg/kg Participants in Part 1 will be confined to the CRU from Day -1 to Day 4, with a single dose of IP administered on Day 1. Participants in Cohort 4 only (the FE cohort) will be recalled, following investigator review of safety data, after a 1-to-2-week washout of their Day 1 dose of IP to assess impact of FE on safety and PK of single dose GT02287. Participants in the FE cohort will be re-admitted to the CRU on FE Day -1 and confined until FE Day 4, with a second single dose of the same allocated treatment on FE Day 1 in a fed state. The enrollment of the next dose cohort will begin only after review of the safety and tolerability data (through Day 4) and available plasma PK data (through the 60-hour post dose sample) for at least 6 out of 8 participants of the previous dose cohort. Part 2 (multiple ascending doses; MAD): This part can begin once safety, tolerability, and PK data are available from the first 3 dose levels from Part 1. Progression to MAD will be confirmed by a blinded Safety Review Committee (SRC). Study participants will be randomly assigned to receive multiple doses of GT 02287 or placebo administered as an oral solution once a day for 14 days. Participants will be confined from Day -1 to Day 17, with once-a-day dosing from Day 1 to Day 14. There will be 4 ascending dose cohorts in this part with 8 healthy adult participants per cohort. The sentinel dosing will not be used, and all participants will be directly randomized in a 3:1 ratio (6 participants will receive GT-02287 and 2 will receive placebo). - Cohort 1: 2.4 mg/kg/day - Cohort 2: 4.8 mg/kg/day - Cohort 3: 7.7 mg/kg/day - Cohort 4: 10 mg/kg/day For all cohorts in both parts, all doses of IP will be administered in a fasted state (other than the second dose for the FE cohort). In Part 1, participants will fast overnight for at least 10 hours before their dose in the morning, followed by an additional 4-hour postdose fast. In Part 2, participants will fast for at least 8 hours overnight predose, followed by an additional 4-hour postdose fast. Water will be allowed as often as desired except for the intervals from 1 hour before dosing to 1 hour after dosing. The second dose of the FE cohort in part 1 will be used to evaluate single-dose PK under fed conditions. Before their dose in the morning, participants will fast for at least 10 hours overnight, then eat a high-fat (=50 percent of total caloric content of the meal), high-calorie (approximately 800 to 1000 calories) meal 30 minutes prior to dose administration. The high-fat meal should be consumed within 30 minutes or less and IP should be administered 30 minutes after the start of the meal. Participants will then fast for at least 4 hours postdose. Water will be allowed as often as desired except the intervals from 10 minutes before dosing to 1 hour after dosing. Individual doses will be provided for participants by Clinical Reasearch Unit staff on the day of administration in 60 mL amber glass bottles with a polypropylene top seal and screw cap. All participants will receive the IP at the study site under the surveillance of appropriate study personnel.
Sponsors
Gain Therapeutics, Australia Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participant must be able and willing to provide written informed consent and be willing to comply with the requirements and restrictions of the study. 2. Participant is of any sex, >/=18 and < /=65 years of age. 3. Participant has a body mass index >/=18 and < /=32 kg/m2 at Screening. 4. Participant is not pregnant and not lactating. 5. If participant is either of childbearing potential or produces potentially viable sperm, participant must agree to use 2 forms of contraception (barrier method and a second highly effective form of birth control/contraception, as per definitions below) if engaging in potentially reproductive intercourse (with a partner who produces potentially viable sperm or is of childbearing potential, respectively) from Screening until at least 30 or 90 days respectively following final study dose administration: - Barrier method: condom, diaphragm or cap AND - Second highly effective form of birth control/contraception: established use of oral, injected, intravaginal, or implanted hormonal contraception (combined or progestogen-only, associated with inhibition of ovulation), intrauterine device, or intrauterine hormone-releasing system Note: A participant is considered to be of childbearing potential if they are postmenarchal and premenopausal, unless surgically sterile (permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or physiologically incapable of becoming pregnant. A postmenopausal state is defined as no menses for at least 1 year without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration >/= 40 IU/L. 6. Participant must agree to not donate ova or sperm from Screening until at least 30 or 90 days respectively following final study dose administration. 7. Participant must agree to not participate in another investigational study while taking part in this study.
Exclusion criteria
1. Participant has a suspected hypersensitivity to GT-02287 or excipients. 2. Participant has AST, ALT, alkaline phosphatase [ALP], gamma-glutamyl transferase [GGT] or TBIL >1.5 × ULN at Screening. If a participant is initially excluded due to this criterion, the assessment may be repeated once at the investigator’s discretion prior to Day -1. 3. Participant has any clinically significant history of allergies (including drug allergies, allergic eczema, or anaphylactic reactions, but excluding untreated allergic rhinitis or rhinoconjunctivitis caused by seasonal or house dust mite allergy). 4. Participant has a history of suicidal behavior or suicide attempts (an answer of “yes” to any lifetime suicidal behaviors on the C-SSRS), has had any active suicidal ideation within the last 3 months before Screening (an answer of “yes” to categories 4 or 5 of the C SSRS), or who is at significant risk to commit suicide, as judged by the investigator using the C-SSRS at Screening. 5. Participant has or had an active febrile illness or a symptomatic viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 2 weeks before Day -1. 6. Participant has any clinically significant abnormality following the Investigator’s review of the physical examinations, ECG, and clinical laboratory tests at Screening or on Day -1. If a participant is initially excluded due to this criterion, the assessment may be repeated once at the investigator’s discretion prior to Day -1. 7. Participant has the below mean pulse rate, systolic blood pressure (SBP), or diastolic blood pressure (DBP) when measured at rest in triplicate at Screening or Day -1: - Mean pulse rate <45 or >100 beats per minute. - Mean SBP >160 mmHg. - Mean DBP >95 mmHg. If the mean pulse, mean SBP, or mean DBP is out of the range specified above, 1 additional triplicate measurement may be taken at Screening or on Day -1. If this triplicate also gives an abnormal result, the participant should be excluded. 8. Participant has a mean QT interval corrected using Fridericia’s Formula (QTcF) of >450 msec (for males) and >470 msec (for females) at Screening or Day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken. If this triplicate also gives an abnormal result, the participant should be excluded. 9. Participant has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsade de pointes, structural heart disease, or a family history of long QT syndrome. 10. Participant has a history of seizures, head trauma, or loss of consciousness. 11. Participant uses any prescribed or nonprescribed drugs (including vitamins, dietary supplements, hormone replacement therapy, natural and herbal remedies, e.g., St. John’s Wort) within 2 weeks or 5 half-lives (whichever is longer) before Day -1. Paracetamol at doses up to 2 g/day and hormonal birth control/contraception is allowed. 12. Participant has used cigarettes (or equivalent nicotine-containing product) within 4 weeks prior to Screening or has urine cotinine >200 ng/mL level at Screening or on Day -1. If a participant is initially excluded due to this criterion, the assessment may be repeated once at the investigator’s discretion prior to Day -1. 13. Participant has a history of consuming more than 14 units of alcoholic beverages per week (note: 1 unit equal to 250 mL of beer, 100 mL of wine, or 30 mL of spirits/hard liquor) within 6 months prior to Screening, has a history of alcoholism within 2 years prior to Screening, or has a positive alcohol breath test at Screening or Day -1. If a participant has a positive alcohol breath test at Screening, the assessment may be repeated once at the investigator’s discretion prior to Day -1. A positive test on Day 1 is exclusionary. 14. Participant has excessive caffeine consumption (defined as greater than 4 cups per day of caffeinated coffee, tea, soda, energy drinks and/or other beverages containing caffeine, or equivalent in chocolate, supplements, or other sources of caffeine) within 2 weeks prior to Day -1. 15. Participant is unable to refrain from consumption of grapefruit, grapefruit juice, Seville oranges, star fruit, or pomelo fruit within 7 days prior to Day 1 and for the duration of the study. 16. Participant has used amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates (drugs of abuse) within 3 months before Day -1 or has a positive urine drug screen at Screening or Day -1. If a participant has a positive urine drug screen at Screening, the assessment may be repeated once at the investigator’s discretion prior to Day -1. 17. Participant has used medications known to interfere with the CYP3A4 and/or P-glycoprotein metabolic pathways in the 3 months prior to Day -1. 18. Participant has used dietary supplements or herbal remedies known to interfere with the CYP3A4 and/or P-glycoprotein metabolic pathways in the 4 weeks prior to Day -1. 19. Participant has had any significant blood loss (equal to 450 mL), donated 1 unit (equal to 450 mL) of blood, or received a transfusion of any blood or blood products within 60 days before Day -1, or has donated plasma within 7 days before Day -1. 20. Participant has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis A virus immunoglobulin M antibodies (anti-HAV IgM), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus 1 and 2 antibodies (anti-HIV-1, anti-HIV-2). 21. Participant has a history of malabsorption, inflammatory bowel disease, pancreatitis, irritable bowel disease, cholecystectomy, Gilbert’s Syndrome, or any other clinically relevant disorder which may impact the absorption of GT 02287. 22. Participant has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy, as judged by the investigator or designee. A history of childhood asthma that is resolved (in the opinion of the investigator) is not exclusionary. 23. Participant has current or recent history (within the past 6 months) of recurrent headache (e.g., tension-type, cluster, or migraine with a frequency of >/=2 episodes per month and requiring treatment), which, in the opinion of the investigator, precludes participation in the study. 24. Participant has a history of severe depression, or mild/moderate depression lasting >/=3 months, requiring hospitalization and/or pharmacological therapy, or recent history (within the past 6 months) of any other psychiatric condition which, in the opinion of the investigator, precludes participation in the study. 25. Participant’s estimated glomerular filtration rate (calculated based on Cockcroft-Gault formula) is <60 mL/min/1.73 m2. 26. Participant has participated in any interventional clinical study or has been treated with any investigational drugs within 3 months or 5 half-lives, whichever is longer, before Screening. 27. Participant is an employee of the Gain Therapeutics group, or any vendor involved in the study. Food effect cohort exclusion criterion: 28. Participant has any allergies, intolerances, or dietary preferences that prevents them from consuming the high-fat breakfast.
Outcome results
None listed