Autism Spectrum Disorder (ASD), Idiopathic Pulmonary Fibrosis (IPF), Glioma & Breast Cancer Not Applicable
Conditions
Interventions
This is a randomised, double-blinded, placebo-controlled dose-escalation study to evaluate the safety, tolerability, PK, and PD of the tablet formulation of SFX-01 following single and repeat daily do
Sponsors
Evgen Pharma (United Kingdom)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Participants who are able to provide informed consent indicating they understand the purpose of, and procedures required, for the study and are willing to participate. 2. Participant must be 18 to 55 years of age inclusive, at the time of signing and dating the informed consent form (ICF). 3. Participants must be male. 4. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, safety laboratory tests, vital signs, and 12-lead ECGs. 5. Participants must have a body mass index (BMI) of 18-32 kg/m2, with body weight in the range of 50-100 kg. 6. Male participant (and partner of childbearing potential) willing to use a highly effective method of contraception or 2 effective methods of contraception, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the participant) from first dose until 90 days after last dose of IMP. To be re-confirmed on Day -8 (prior to skin punch biopsy) and Day -1 (prior to first dose administration): 7. Participant continues to meet all screening inclusion criteria. 8. Participant has a negative urinary drugs of abuse (DOA)/alcohol screen. 9. Participant has a negative COVID-19 test (if required at the time of study conduct).
Exclusion criteria
Exclusion criteria: 1. Participants who are unable to refrain from eating brassica vegetables or using brassica containing supplements from at least 7 days prior to the Day -8 skin punch biopsies until the End of- Study Visit. Brassica vegetables include cabbage, cauliflower, horseradish, landcress, Ethiopian mustard, kale, collard greens, Chinese broccoli, cabbage, Brussels sprouts, Kohlrabi broccoli, broccoli flower, broccoli romanesco, wild broccoli, bok choy, Komatsuna, mizuna, rapini, flowering cabbage, Chinese cabbage, Napa cabbage, turnip root, rutabaga, canola/rape seed, Siberian kale, wrapped heart mustard cabbage, mustard seed (brown, black, white), tatsoi, rocket (arugula), garden cress, water cress, radish, daikon, and wasabi. 2. Participants with a known sensitivity or intolerance to brassica vegetables. 3. Participants with any clinically relevant history (e.g., respiratory, renal, hepatic, GI, haematological, lymphatic, neurological, cardiovascular, psychiatric disease or diseases). 4. Participants with any clinically significant abnormal vital signs, physical examination, or other safety findings within 36 days before the first dose administration of the IMP. 5. Participants with any clinically significant abnormal test results for haematology, clinical chemistry, coagulation and/or urinalysis within 36 days before the first dose administration of the IMP. 6. Participants with gamma-glutamyl transferase (GGT) >1.5 x upper limit of normal (ULN). 7. Participants with disorders of the central nervous system, psychiatric disorders, and/or behavioural disturbances (e.g., cerebrovascular events, depression, post-traumatic stress disorder, anxiety, bipolar disorder, severe migraine, and Parkinson's disease). 8. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements, within 36 days or 5 half-lives (whichever is longer) prior to the first dose of IMP. 9. Participants with a positive screen for Hepatitis B (Hepatitis B surface antigen [HBsAg]), Hepatitis C (Hepatitis C antibody, anti-Hepatitis C virus [HCV]), COVID-19 (lateral flow test [LFT]) or human immunodeficiency virus (HIV). 10. Participants with a history or clinical evidence of alcoholism or drug abuse. Alcohol abuse is defined as regular weekly intake of more than 21 units if male. Drug abuse is defined as compulsive, repetitive and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a reduction in dose will lead to withdrawal symptoms. 11. Participants who smoke more than 10 cigarettes or the equivalent amount of tobacco per day and/or regularly use vaping products and/or are unwilling to refrain from smoking/vaping during the study. 12. Participants with a confirmed positive result from urinary DOA screen at Screening, Day -8, or Day -1 indicating drug abuse including amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, methadone, opiates, phencyclidine (PCP), and tricyclic antidepressants, or a confirmed positive urine alcohol test at Screening, Day -8, or Day -1. 13. Participants who have received a COVID-19 vaccination within 28 days prior to the first dose or plan to receive a COVID-19 vaccination before the End-of-Study Visit. 14. Participants who had donated more than 500 mL of blood within 90 days prior to Screening. 15. Participation in a New Chemical Entity (NCE) clinical study within the previous 3 months or five half-lives, whichever is longer, or a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoints for this study are safety endpoints and are defined as follows: 1. Adverse Events (AEs) will be recorded from the point of informed consent up to final post-study follow up visit. 2. Laboratory safety (biochemistry, haematology, coagulation and urinalysis) at screening, Day -8, Day -1, Day 4, Day 7 & End of Study 3. Vital signs (systolic/diastolic blood pressure, pulse, oral body temperature and respiratory rate) at screening, Day -8, Day -1, Day 1 (pre-dose and 1, 2, 4, 8 and 12 h post dose), Day 4, Day 7 (pre-dose and 1, 2, 4, 8, and 12 h post-dose), and End-of Study Visit 4. 12-lead ECG (heart rate, PR interval, QRS width, QT interval and QTcF interval) at screening, Day -1, Day 1 (Pre-dose, 2, 4, 8, and 12 h post dose), Day 2, Day 4, Day 7, and End-of Study Visit | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints for this study are pharmacokinetic/pharmacodynamic parameters derived from analysis of plasma and urine samples for concentrations of SFX-01 and its' major metabolites. PK Endpoints are defined as follows: 1.1. Single Dose (Day 1) AUC0-12 - area under the concentration-time curve from 0 to 12 hours AUC0-24 - area under the concentration-time curve from 0 to 24 hours Cmax - maximum observed concentration AUC0-12 (norm) - area under the concentration-time curve from 0 to 12 hours normalised for dose AUC0-24 (norm) - area under the concentration-time curve from 0 to 24 hours normalised for dose Cmax (norm) - maximum observed concentration normalised for dose C24 - concentration at 24 hours (pre-dose Day 2) Tmax - time to maximum observed concentration t½ - apparent terminal elimination half-life ?z - terminal elimination rate constant CL/F - Apparent total body clearance following extravascular administration (parent only) Vz/F - apparent volume of distribution in the terminal state (parent only) Ae - amount excreted in urine fe - fraction excreted in urine (parent only) CLR - renal clearance 1.2. Steady-State (Day 7) AUCtau - area under the concentration-time curve in the dosing interval AUC0-8 - area under the concentration-time curve from time 0 extrapolated to infinity %AUCext - percentage extrapolated AUC Cmax,ss - maximum observed concentration at steady-state Cmin,ss - minimum observed concentration at steady-state AUCtau (norm) - area under the concentration-time curve in the dosing interval normalised for dose AUC0-8 (norm) - area under the concentration-time curve from time 0 extrapolated to infinity normalised for dose Cmax,ss (norm) - maximum observed concentration at steady-state normalised for dose Cmin,ss (norm) - minimum observed concentration at steady-state normalised for dose Tmax,ss - time to maximum observed concentration at steady state t½ - apparent terminal elimination half-life ?z - terminal elimination rate constant C | — |
Countries
United Kingdom
Outcome results
None listed