Epilepsy Nervous System Diseases Epilepsy
Conditions
Interventions
On Days 1 to 20, volunteers will receive single oral doses of the non-radiolabelled test medicine, SPN 817 Extended Release Capsules, twice daily, in the morning and evening. To increase tolerance to
Sponsors
Supernus Pharmaceuticals (United States)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Healthy males 2. Aged 30 to 64 years inclusive at the time of signing informed consent 3. Body mass index (BMI) of 18.0 to 32.0 kg/m² as measured at screening 4. Must be willing and able to communicate and participate in the whole study 5. Must have regular bowel movements (ie average stool production of =1 and =3 stools per day) 6. Must provide written informed consent 7. Must agree to adhere to the contraception requirements defined in the clinical protocol
Exclusion criteria
Exclusion criteria: 1. Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer 2. Subjects who are, or are immediate family members of, a study site or sponsor employee 3. Subjects who have previously been administered IMP in this study 4. Evidence of current SARS-CoV-2 infection 5. History of any drug or alcohol abuse in the past 2 years 6. Regular alcohol consumption >21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 ml glass of wine, depending on type) 7. A confirmed positive alcohol breath test at screening or admission 8. Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission 9. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months 10. Male subjects with pregnant or lactating partners 11. Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study 12. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 13. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert’s Syndrome are not allowed. 14. Confirmed positive drugs of abuse test result 15. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results 16. Evidence of renal impairment at screening, as indicated by an estimated CLcr of <80 mL/min using the Cockcroft-Gault equation 17. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator 18. Resting heart rate <50 bpm at screening 19. History of bladder outflow obstruction such as benign prostatic hyperplasia or any history of acute urinary retention 20. Creatine kinase =1.5 x upper limit of normal 21. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients 22. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active 23. Donation of blood or plasma within the previous 3 months or loss of greater than 400 ml of blood 24. Subjects who are taking, or have taken, any prescribed or over-the-counter drug, or herbal remedies or vaccines, including the COVID-19 vaccine, (other than up to 4 g of paracetamol per day) in the 14 days before IMP administration. Exceptions may apply, as determined by the investigator, if each of the following criteria are met: medication with a sho
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Mass balance of total radioactivity recovery in all excreta (urine and faeces): CumAe and Cum%Dose measured using mass spectrometry from samples taken at timepoints between Day 22 and Day 29 2. Metabolite profiling, structural identification, and quantification analysis in whole blood, plasma, urine and faeces samples using liquid chromatography-radio-detection with subsequent mass spectrometry where appropriate, from samples taken at timepoints between Day 22 and Day 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Determination of routes and rates of elimination of total radioactivity (TR) by Ae, %Dose, CumAe and Cum%Dose by interval from blood, urine and faecal samples taken at timepoints between Day 22 and Day 29 2. Identification of the chemical structure of each metabolite accounting for more than 10% by AUC of circulating TR or 10% of the excreted dose from blood, urine and faecal samples taken at timepoints between Day 22 and Day 29 3. Evaluation of whole blood:plasma concentration ratios for TR from samples taken at timepoints between Day 22 and Day 29 3. Measurement of appropriate pharmacokinetic (PK) parameters of huperzine A in plasma and whole blood, including but not limited to: tlag, tmax, tlast, Cmax, AUCtau, AUClast, t1/2, Lambda-z, CL/Ftau, Vz/Ftau, MRTlast, whole blood:plasma concentration ratios for huperzine A, where possible and applicable from samples taken at timepoints between Day 1 and Day 29 4. Measurement of appropriate PK parameters of huperzine A in urine including but not limited to: Ae, CumAe, Fe%, CumFe% and CLR, where possible from samples taken at timepoints between Day 1 and Day 29 5. Measurement of appropriate PK parameters of TR in plasma and whole blood, including but not limited to: tlag, tmax, tlast, Cmax, AUClast, AUCinf, t1/2, Lambda-z, B/P AUC, where possible and applicable from samples taken at timepoints between Day 22 and Day 29 6. Safety and tolerability information for SPN-817 by assessing the incidence of adverse events (AEs), concomitant medications, physical examinations, medical history, change from baseline for vital signs, electrocardiograms (ECGs), suicidal ideation and behaviour as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) and laboratory safety tests at screening and from Day -1 until discharge from the ward on (up to) Day 29 | — |
Countries
England, United Kingdom
Outcome results
None listed