Healthy volunteers Not Applicable
Conditions
Interventions
The study incorporated five drug-drug interaction (DDI) investigations with REN001 and five different NIMPs as follows
gemfibrozil (Part A), fluconazole (Part B), fexofenadine (Part C), rosuvastatin (Part D) and carbamazepine (Part E
optional). Part A, Part B and Part E enrolled single cohorts containing up to 14 subjects each, Part C enrolled two cohorts containing up to 24 subjects, and Part D enrolled a single cohort containing
Day -35 to Day -1)
Screening assessments were performed from Day -35 to Day -1 to ensure the eligibility of subjects.
Part A (REN001 and gemfibrozil)
Day -1 to Day 5
Subjects entered the Clinical Pha
Sponsors
Reneo Pharma Ltd (United Kingdom)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy male and female subjects, between 18 and 60 years of age, inclusive. 2. Female subject with a negative pregnancy test at Screening. 3. Subjects must agree to adhere to the contraception requirements defined in the study protocol. 4. Subject with a body mass index (BMI) of 18-32 kg/m2 (BMI = body weight (kg) / [height (m)]2) 5. No clinically significant history of previous allergy/sensitivity to REN001, gemfibrozil, fluconazole, fexofenadine, rosuvastatin, carbamazepine or any of the excipients contained within the IMP/NIMPs. 6. No clinically significant abnormal test results for serum biochemistry, haematology, coagulation and/or urine analyses within 35 days before the first dose administration of the IMP/NIMP. 7. Subject with a negative urinary drugs of abuse (DOA) screen (including alcohol) test results, determined within 35 days before the first dose administration of the IMP/NIMP (N.B.: A positive test result may be repeated at the Investigator’s discretion). 8. Subject with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg)) and hepatitis C virus antibody (HCV Ab) test results at Screening. 9. No clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 35 days before first dose of IMP/NIMP including a PR interval >220 ms, QT interval heart rate corrected using Fridericia’s formula QTcF >450 ms. 10. No clinically significant abnormalities in vital signs (e.g., blood pressure, pulse, respiratory rate and oral temperature) determined within 35 days before first dose of IMP/NIMP. 11. Subject must be available to complete the study (including all follow-up visits). 12. Subject must satisfy an Investigator about his/her fitness to participate in the study. 13. Subject must provide written informed consent to participate in the study.
Exclusion criteria
Exclusion criteria: 1. A clinically significant history of gastrointestinal disorder likely to influence IMP/NIMP administration and absorption. 2. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 35 days or 5 half-lives (whichever is longer) prior to the first dose of IMP/NIMP with the exception of paracetamol (which may be taken as an analgesic to a maximum of 2 g in 24 h) and ibuprofen (which may be taken as an analgesic to a maximum of 1.2 g in 24 h [400 mg 3 times a day]). 3. Subjects who have previously received REN001. 4. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction. 5. Suitable veins for venepuncture and cannulation. 6. Presence or history of clinically significant allergy requiring treatment, as judged by the Investigator. Hay Fever is allowed unless active. 7. A clinically significant history of drug or alcohol abuse (defined as the consumption of more than 14 units [for male and female subjects] of alcohol a week) within the past two years. 8. Medical history that would preclude the administration of the NIMPs. 9. Inability to communicate well with the Investigators (i.e., language problem, poor mental development or impaired cerebral function). 10. Participation in a New Chemical Entity (NCE) clinical study within the previous 3 months or five half-lives, whichever is longer, or a marketed drug clinical study within 30 days or five half-lives, whichever is longer, before the first dose of IMP/NIMP. (The washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study). 11. Donation or loss of 450 mL or more blood within the 3 months before the first dose of IMP/NIMP or no plans to donate blood in the 3 months following completion of the study. 12. Vegans, vegetarians or other dietary restrictions (e.g., restrictions for medical, religious or cultural reasons, etc) that would prevent the subject from consuming a standardised meal or gelatine capsule. 13. Willing and able to swallow gelatin capsules. 14. Users of nicotine products i.e., current smokers or ex-smokers who have smoked within the 6 months prior to Screening or users of cigarette replacements (i.e., e-cigarettes, nicotine patches or gums). 15. Female subjects who are pregnant, breastfeeding or lactating. 16. Subjects who have received a COVID-19 vaccine injection within 35 days prior to the first dose of IMP/NIMP.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) parameters derived from analysis of plasma samples for concentrations of REN001 and its metabolites (M351 and M527) in Parts A, B & E, fexofenadine in Part C and rosuvastatin in Part D: 1. Cmax - Maximum plasma concentration 2. Tmax - Time of Cmax 3. t½ - Terminal elimination half-life 4. AUC0-t - Area under the plasma concentration-time profile from time zero to the time of the last measurable concentration (Clast) 5. AUCinf - Area under the plasma concentration-time profile from time zero extrapolated to infinite time 6. AUC0-t metabolite to parent ratios (REN001 only) - AUC0-t (metabolite) / AUC0-t (REN001) 7. AUCinf metabolite to parent ratios (REN001 only) - AUCinf (metabolite) / AUCinf (REN001) In addition, ?z, CL/F, Vz/F, AUC%extrapolated will be derived and reported for REN001 (and its metabolites) fexofenadine and rosuvastatin. Blood samples for PK analysis were taken at the following timepoints: Part A: 71 timepoints from Day 1 pre-dose to Day 33 Part B: 37 timepoints from Day 1 pre-dose to Day 18 Part C/D: 36 timepoints from Day 1 pre-dose to Day 16 Part E: 34 timepoints from Day 1 pre-dose to Day 25 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety endpoints defined as follows: 1.1. Adverse events (AEs) recorded from the point of informed consent up to the final post-study follow-up visit in each part 1.2. Laboratory safety (biochemistry, haematology, coagulation and urinalysis) 1.3. Vital signs (systolic/diastolic blood pressure, pulse, oral body temperature and respiratory rate) 1.4. 12-lead ECG (heart rate, PR interval, QRS width, QT interval and QTcF interval) Safety endpoints will be evaluated at set points within the following periods: Part A: screening to post-study follow-up (up to Day 39) Part B: screening to post-study follow-up (up to Day 24) Part C/D: screening to post-study follow-up (up to Day 22) Part E: screening to post-study follow-up (up to Day 31) 2. Pharmacokinetic parameters derived from analysis of plasma samples for concentrations of Coproporphyrin I (for Part A only): 2.1. Cmax - Maximum plasma concentration 2.2. Tmax - Time of Cmax 2.3. AUC0-24 - Area under the plasma concentration-time profile from time zero to 24 hours post-dose Blood samples for PK analysis of secondary endpoints were taken at the following timepoints: Part A: 13 timepoints from Day 1 pre-dose to 24 hours post-dose | — |
Countries
United Kingdom, Wales
Contacts
Public ContactStudy Clinical Trial Coordinator
Outcome results
None listed