A 3-part Study to Evaluate Safety, Tolerability, Food Effect and Drug-drug Interactions of RXC007 in Healthy Volunteers
Condition: Fibrosis; Inflammation; Idiopathic Pulmonary Fibrosis; Non-alcoholic Steatohepatitis; Liver Diseases; Kidney Diseases
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Kidney Diseases; Fibrosis; Inflammation
Study type: Interventional
Phase: Phase 1

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

Detailed description: 
      The study will be split into 3 parts: Part A, Part B & Part C.

      The overall study will enrol up to 136 healthy males; maximum of 68 in Part A, maximum of 44
      in Part B and maximum of 24 in Part C.

      The purpose of Part A is to evaluate the safety, tolerability and concentration of RXC007 in
      the blood when it is given as a single dose on one occasion at different dose strengths. In
      addition, one group in Part A will investigate the effect of food on the safety, tolerability
      and concentration of RXC007 in the blood by taking a single dose of RXC007 following an
      overnight fast and then following a high fat breakfast. Part A will consist of 6 planned
      groups of 6 participants: each group investigating a different dose strength starting at the
      lowest dose and gradually increasing in each group. If required and determined as necessary
      following dose escalation data review, Part A may enrol up to a maximum of 4 additional
      cohorts with a maximum of 8 participants within each cohort.

      Part A of the study will consist of a screening visit (between 28 and 2 days prior to first
      dose), a treatment period (consisting of a maximum of 5 days with 4 overnight stays) and a
      post-study follow-up visit on Day 15. For the food effect cohort, an additional treatment
      period (consisting of a maximum of 5 days with 4 overnight stays) will be undertaken
      following an approximately 4-week washout period with a second follow-up visit to be
      conducted on Day 15 following the second treatment period.

      The purpose of Part B is to evaluate the safety, tolerability and concentration of RXC007 in
      the blood when it is given as a single dose once a day for a period of 14 days at different
      dose strengths. Part B will consist of up to 2 planned groups of 6 participants; each group
      investigating a different dose strength based on the data generated during Part A of the
      study. If required and determined as necessary following dose escalation data review, Part B
      may enrol up to a maximum of 4 additional cohorts with a maximum of 8 participants within
      each cohort.

      Part B of the study will consist of a screening visit (between 28 and 2 days prior to first
      dose), a treatment period (consisting of a maximum of 18 days with 17 overnight stays) and a
      post-study follow-up visit on Day 28.

      Within each cohort in Part A and Part B, 4 participants will receive RXC007 with the
      remaining 2 participants receiving a matching placebo. Each cohort will follow a dose leader
      schedule, whereby 2 participants (1 active, 1 placebo) will be dosed a minimum of 24 hours
      prior to the remaining 4 participants in the cohort. Between each cohort, safety and PK data
      up to the 72-hour post-last dose time point for Part A and up to Day 17 in Part B will be
      evaluated by a Dose Escalation Review Committee (DERC) to determine whether it is appropriate
      to dose escalate into the next cohort. If required, i.e., the safety or pharmacokinetics (PK)
      data indicates, dose modifications may be made in order to select an intermediate/lower dose.
      In addition, modifications may be made following both treatment periods for the food effect
      cohort in Part A to dose all remaining cohorts in Part A and Part B in a fed state (with a
      standardised breakfast) and in Part B, the dose regime may be modified in terms of frequency
      to increase dosing from once per day to multiple times per day. In addition, decisions may be
      made that the proposed length of the in-house treatment period in both Part A & Part B should
      be reduced by one day (from Day 4 to Day 3 in Part A and from Day 17 to Day 16 in Part B).

      The purpose of Part C is to evaluate the safety, tolerability and effect of RXC007 on the
      concentration of rosuvastatin and metformin in the blood to determine as to whether RXC007
      affects the activity of the processes by which certain types of drugs are broken down
      (metabolised) in the body and therefore, whether RXC007 has the potential to interact with
      other drugs, affecting their desired effect in the body i.e., evaluating the drug-drug
      interaction potential of RXC007.

      Part C will consist of 2 groups of 12 participants; Group 1 evaluating the drug-drug
      interactions of RXC007 and rosuvastatin (at a dose strength of 10 mg in an oral tablet
      formulation) and Group 2 evaluating the drug-drug interactions of RXC007 and metformin (at a
      dose strength of 500 mg in an oral tablet formulation). The dose strength of RXC007 to be
      evaluated will be selected based on review of the data generated in Part B of the study.

      Part C of the study will consist of a screening visit (between 28 and 2 days prior to first
      dose), a treatment period (consisting of either a maximum of 14 days with 13 overnight stays
      for Group 1 or a maximum of 11 days with 10 overnight stays for Group 2) and a post-study
      follow-up visit approximately 14 days following the last dose of RXC007 with rosuvastatin or
      metformin (either Day 23 or Day 21 respectively for Group 1 and Group 2).
    

Intervention name(s): RXC007; RXC007 Matching Placebo
Intervention type(s): Drug; Drug
Intervention description(s): RXC007 will be administered in the form of oral capsules at selected doses starting at 2 mg to 4 of the 6 participants within each cohort in Part A and Part B. For Part A, dosing frequency is one single dose on one occasion and for Part B, dosing frequency is single doses once daily for 14 days. If required, following dose escalation data review, dosing frequency and duration may be modified in Part B.
All participants in Part C (24) will receive active RXC007 in the form of oral capsules as single doses.; The matching placebo for RXC007 will be administered in the form of oral capsules matched to the number of active RXC007 capsules at each dose level to 2 of the 6 participants within each cohort in Part A and Part B. For Part A, dosing frequency is one placebo dose on one occasion and for Part B, dosing frequency is single placebo doses once daily for 14 days. If required, following dose escalation data review, dosing frequency and duration may be modified in Part B.
There is no placebo intervention for Part C of the study.
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: 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.
In 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment