Primary mitochondrial myopathy (rare genetic diseases that cause muscles to not function properly) Genetic Diseases
Conditions
Interventions
Participants receive one 100 mg oral dose of [14C]-REN001 oral solution in the fasted state
Sponsors
Reneo Pharma Ltd
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Healthy males 2. Aged 30 to 65 years, inclusive, at the time of signing informed consent 3. Body mass index (BMI) of 18.0 to 30.0 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 (i.e. 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 within 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 report to have previously received REN001 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 in males >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. 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 have been administered IMP in an ADME study in the last 12 months 13. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 14. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert’s Syndrome are not allowed. 15. Confirmed positive drugs of abuse test result 16. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results 17. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <80 mL/min using the Cockcroft-Gault equation 18. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator 19. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients 20. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active 21. Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood 22. Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (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 short half-life if the washout is such that no pharmacodynamic activity is expected by the time of dosing with IMP; and if the use of medication does not jeopardize the safety of the trial subject; and if the use of medication is not considered to interfere with the objectives of the study. COVID-19 vaccines are accepted concomitant medications. 23. Failure to satisfy the investigator of fitness to participate for any other reason
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mass balance recovery of total radioactivity in all excreta (urine and faeces): CumAe and Cum%Ae measured using liquid scintillation counting. This is assessed between Day 1 and Day 13, or later if the radioactivity criteria were not met (including additional collections in the clinical unit and/or home collections). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Ae, %Ae, CumAe and Cum%Ae for total radioactivity in all excreta (urine and faeces) by interval measured using liquid scintillation counting. These are assessed between Day 1 and Day 13, or later if the radioactivity criteria were not met (including additional collections in the clinical unit and/or home collections). 2. Identification of the chemical structure of each metabolite accounting for =10% of circulating total radioactivity (plasma) or accounting for =10% of the dose in urine and faeces by liquid chromatography-radio-detection with subsequent high-resolution mass spectrometry where appropriate. This is assessed between Day 1 and Day 13, or later if the radioactivity criteria were not met (including additional collections in the clinical unit and/or home collections). 3. Tlag, Tmax, Cmax, AUC(0-last), AUC(0-inf), lambda-z, T1/2, CL/F (apparent clearance), Vz/F (apparent volume of distribution), metabolite to parent ratios (based on Cmax and AUC), as applicable are measured using liquid chromatography with tandem mass spectrometry. These are assessed between Day 1 and Day 13, or later if the radioactivity criteria were not met (including additional collections in the clinical unit and/or home collections). 4. Evaluation of whole blood:plasma concentration ratios for total radioactivity for corresponding time points measured using liquid scintillation. This is assessed between Day 1 and Day 13, or later if the radioactivity criteria were not met (including additional collections in the clinical unit and/or home collections). 5. Incidence of adverse events (AEs) collected by often asking volunteers how they are feeling and change from baseline for vital signs, electrocardiogram (ECG) parameters, and laboratory safety parameters assessed by standard Phase 1 unit monitoring. These are assessed at screening and throughout the trial. | — |
Countries
England, United Kingdom
Contacts
Public ContactStudy Clinical Trial Coordinator
Outcome results
None listed