A Randomised, Double-blind, Placebo-controlled, SAD/MAD First-in-human, Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of RXC007 Including Evaluation of Drug-Drug Interaction and Food Effect in Male Participants

RXC007/0001

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of RXC007.

2021-05-13

2023-03-08

2023-03-08

Completed

Early phase I

90

Inclusion Criteria: 1. Healthy male participants, between 18 and 55 years of age, inclusive. 2. Male participant (and female 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 3 months after last dose of IMP/NIMP. 3. Participant with a body mass index (BMI) of 18.0-32.0 kg/m2. 4. Participant with a body weight of 60 kg or greater. 5. No clinically significant history of previous allergy / sensitivity to RXC007, rosuvastatin or metformin, or any of the excipients contained within the IMP/NIMP. 6. No clinically significant abnormal test results for serum biochemistry, haematology and/or urine analyses within 28 days before the first dose administration of the IMP/NIMP. 7. Haemoglobin and haematocrit above the lower limit of the normal range for the reference laboratory. 8. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) \< 1.5 times the upper limit of the normal (ULN) range for the reference laboratory. 9. Participant with a negative urinary drugs of abuse (DOA) screen (including alcohol) test results, determined within 28 days before the first dose administration of the IMP/NIMP (N.B.: A positive test result may be repeated at the Investigator's discretion). 10. Participant with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCV Ab) test results at Screening. 11. No clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 28 days before first dose of IMP/NIMP including a PR interval \> 220ms, QRS width \> 120ms and QTcF interval \> 450 ms. 12. No clinically significant abnormalities in vital signs (e.g., blood pressure (systolic blood pressure \> 140 mmHg) / heart rate, respiration rate, oral temperature) determined within 28 days before first dose of IMP/NIMP. 13. Participant must be available to complete the study (including all follow-up visits). 14. Participant must satisfy an Investigator about his fitness to participate in the study. 15. Participant must provide written informed consent to participate in the study. 16. Participants with a negative COVID-19 reverse transcription polymerase chain reaction (RT-PCR) test on admission (if required). Exclusion Criteria: 1. A clinically significant history of gastrointestinal disorder likely to influence IMP/NIMP absorption. 2. A clinically significant history of infection in the last 3 months. 3. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements, antacids (Part C Cohort 1 only), any product known to be a substrate mainly metabolised by CYP enzymes within 28 days or 5 half-lives (whichever is longer) prior to the first dose of IMP/NIMP. 4. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction. 5. Participants who are unable to demonstrate the ability to swallow multiple "dummy" capsules (i.e., an empty gelatin capsules) of the size proposed for administration in a particular cohort/dose level (up to and including size 00). 6. Participant with a glomerular filtration rate less than 80 mL/min/1.73m2 (calculated by Cockcroft-Gault equation. 7. A clinically significant history of drug or alcohol abuse (defined as the consumption of more than 14 units of alcohol a week) within the past two years. 8. Inability to communicate well with the Investigators (i.e., language problem, poor mental development or impaired cerebral function). 9. Participation in a NCE clinical study within the previous 3 months or five half-lives, whichever is longer, or a marketed drug clinical study within the 30 days or five half-lives, whichever is longer, before the first dose of IMP/NIMP. (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). 10. Donation of 450 mL or more blood within the 3 months before the first dose of IMP/NIMP. 11. Vegans, vegetarians or other dietary restrictions (e.g., restrictions for medical, religious or cultural reasons, etc.), which would prevent participants from consuming a high-fat breakfast or standardised meal. 12. 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). 13. Participants who have received a COVID-19 vaccine injection within 28 days prior to the first dose of IMP/NIMP.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'This study is a first-in-human, single ascending (SAD) and multiple ascending dose (MAD) study, including the evaluation of drug-drug interactions. Each cohort will adopt a dose leader design with 2 participants being dosed on the first dosing day of each cohort. Of these 2, 1 will be on active drug and 1 on placebo. The remainder of the cohort will be dosed at least 24 h later pending an acceptable safety profile in the dose-leader group and will contain at least 1 additional placebo participant.\n\nIn both Part A (SAD) and Part B (MAD), sequential cohorts will be exposed to increasing doses of RXC007. Prior to dose escalation between cohorts, safety and PK data from the previous cohort will be reviewed by the Dose Escalation Review Committee (DERC) to determine whether it is appropriate to proceed to the next cohort/dose level.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'Part A \\& Part B of the study will assume a double blind design whereby both study participants and investigators will be blinded to active IMP versus placebo assignment. Within each cohort, 4 participants will be randomised to active versus 2 placebo participants.\n\nPart C of the study will assume an open-label design whereby all participants will receive active RXC007.\n\nA designated individual will generate the randomisation code under the guidance of a statistician. All other site and Sponsor personnel involved in the study will be blinded with regards to the IMP being administered. The Pharmacist (or designee) responsible for the preparation of participant doses and emergency code break envelopes will not be blinded.', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 90, 'type': 'ACTUAL'}}

2023-11-18