Acute Kidney Injury (AKI) Urological and Genital Diseases
Conditions
Interventions
Parts 1 and 2 are randomised, double-blind and placebo controlled assessing single and multiple ascending doses.
Optional Part 3 is a randomised open-label assessment comparing the test medicine to a
Sponsors
Unicycive Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must provide written informed consent 2. Must be willing and able to communicate and participate in the whole study 3. Subjects must be willing and able to swallow multiple capsules 4. Aged 18 to 55 years inclusive at the time of signing informed consent 5. Must agree to adhere to the contraception requirements defined in the clinical protocol 6. Healthy males or healthy females of non-childbearing potential 7. Body mass index (BMI) of 18.0 to 32.0 kg/m² as measured at screening 8. Weight =50 kg at screening 9. Must have a normal blood pressure defined as a systolic BP between 100 and 140 mmHg, diastolic BP between 40 and 90mmHg after 5 mins supine 10. No evidence of postural hypotension (defined as a dizziness / light headedness or a drop is systolic BP >20mmHg or drop in diastolic BP >10 mmHg when assessed 3 minutes after standing
Exclusion criteria
Exclusion criteria: 1. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients 2. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active 3. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator 4. Subjects with a history of cholecystectomy or gall stones 5. Subjects with any past history of gastrointestinal ulceration (e.g. peptic ulcer disease), gastrointestinal haemorrhage, diverticular disease or recent (within 6 months) symptoms of dyspepsia lasting 2 weeks or more 6. Recurrent and recent history of simple faints, vasovagal presyncope/syncope or blackouts 7. Subjects with glucose-6-phosphate dehydrogenase deficiency 8. Subjects with a history of conjunctival or corneal ulceration within the past 12 months. 9. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 10. Evidence of current SARS-CoV-2 infection 11. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert’s Syndrome are not allowed 12. Subjects with elevated potassium above the upper limit of the normal reference range 13. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results 14. Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative highly sensitive urine [or serum] pregnancy test). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle stimulating hormone [FSH] concentration =40 IU/L) 15. 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 16. Subjects who have previously been administered IMP in this study. Subjects who have taken part in Part 1 are not permitted to take part in Parts 2 and 3. Subjects who have taken part in Part 2 are not permitted to take part in Part 3 17. Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood 18. 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 or established HRT) in the 14 days before study medication administration. COVID-19 vaccines are accepted concomitant medications. 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 PD activity is expected by the time of dosing with IMP; and if the use of medication does not jeopardise the safety of the trial subject; and if the use of medication is not considered to interfere with the objectives of the study 19. Subjects who are using PDE5 inhibitors 20. History of any drug or alcohol abuse in the past 2 years 21. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units =
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability will be assessed throughout the study, from dosing to follow up visits (Day 1 to Day 11 in Part 1 and Part 3, Day 1 to Day 15 in Part 2) Part 1: To provide safety and tolerability information for UNI-494 by assessing: incidence of adverse events (AEs), physical examination findings and change from baseline for vital signs, electrocardiograms (ECGs), and laboratory safety tests Part 2: To provide safety and tolerability information for UNI-494 by assessing: incidence of AEs, physical examination findings and change from baseline for vital signs, ECGs, and laboratory safety tests Part 3 (optional): Nicorandil relative bioavailability (Frel) based on a within subject comparison for Cmax, AUC(0-last) and AUC(0-inf) of the UNI-494 Capsule compared to the nicorandil marketed product (tablet) through measurement of plasma samples taken in Part 3 from dosing to discharge, across both periods. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic parameters will be measured using analysis of plasma samples taken from pre-dose to 48 hours post-dose in all Parts. Relative bioavailability will be assessed through measurement of plasma samples taken in Regimen E, should this be utilised. Samples will be taken from pre-dose to 48 hours post-dose in both periods. Safety and tolerability will be assessed throughout the study, from dosing to follow up visits (Day 1 to Day 11 in Part 3). Part 1: 1.1. Following PK parameters for UNI-494, nicorandil and 1-cyclohexylethylamine will be calculated (where possible and appropriate): Tlag, Tmax, Cmax, C24, AUC(0-24), AUC(0-last), AUC(0-inf), AUCextrap, Lambda-z, T1/2, metabolite to parent ratios (MPR) based on AUC and Cmax, CL/F, Vz/F and MRT 1.2. Relative bioavailability based on a within cohort comparison for Cmax, AUC(0-last) and AUC(0-inf) for UNI-494, nicorandil and 1-cyclohexylethylamine following dosing of the UNI-494 capsule in the fed versus the fasted state Part 2: Following PK parameters for UNI-494, nicorandil and 1-cyclohexylethylamine will be calculated (where possible and appropriate) Tlag, Tmax, Cmax, C24, AUC(0-tau), AUC(0-last), Lambda-z, T1/2, metabolite to parent ratios (MPR) based on AUC and Cmax, accumulation ratios based on Cmax and AUC, CL/Ftau, Vz/Ftau and MRT Part 3 (optional) 3.1. Following PK parameters for UNI-494, nicorandil and 1-cyclohexylethylamine will be calculated (where possible and appropriate): Tlag, Tmax, Cmax, C24, AUC(0-24), AUC(0-last), AUC(0-inf), AUCextrap, Lambda-z, T1/2, metabolite to parent ratios (MPRs) based on AUC and Cmax, CL/F, Vz/F and MRT 3.2. To provide further safety and tolerability information for UNI-494 by assessing: incidence of AEs, physical examination findings and change from baseline for vital signs, ECGs, and laboratory safety tests | — |
Countries
England, United Kingdom
Outcome results
None listed