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A 3-part Study to Evaluate Safety, Tolerability, Food Effect and Drug-drug Interactions of RXC007 in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT04931147
Recruitment Status : Recruiting
First Posted : June 18, 2021
Last Update Posted : June 18, 2021
Sponsor:
Collaborator:
Simbec Research
Information provided by (Responsible Party):
Redx Pharma Plc

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

Condition or disease Intervention/treatment Phase
Fibrosis Inflammation Idiopathic Pulmonary Fibrosis Non-alcoholic Steatohepatitis Liver Diseases Kidney Diseases Drug: RXC007 Drug: RXC007 Matching Placebo Phase 1

Detailed Description:

The study will be split into 3 parts: Part A, Part B & Part C.

Parts A and B of this study will enrol up to 80 healthy males; maximum of 52 in Part A, maximum of 28 in Part B. The sample size to be enrolled in Part C will be determined as Parts A & B are ongoing.

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 2 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 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 2 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).

At this stage of the study, the details of the design, conduct and implementation of Part C are still to be determined and will be implemented via substantial amendment.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
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)
Masking Description:

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.

A 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.

Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 13, 2021
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: Part A SAD - Cohort 1
This is the first treatment arm in Part A (Single Ascending Dose) of the study. 4 participants will be randomised to receive 2 mg of RXC007 on one occasion on Day 1. The remaining 2 participants will receive matching placebo.
Drug: RXC007
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.

Drug: RXC007 Matching Placebo
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.

Experimental: Part A SAD - Cohort 2
This is the second treatment arm in Part A (Single Ascending Dose) of the study. 4 participants will be randomised to receive a selected dose of RXC007 (following Cohort 1 Dose Escalation Data Review) on one occasion on Day 1. The remaining 2 participants will receive matching placebo.
Drug: RXC007
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.

Drug: RXC007 Matching Placebo
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.

Experimental: Part A SAD - Cohort 3
This is the third treatment arm in Part A (Single Ascending Dose) of the study. 4 participants will be randomised to receive a selected dose of RXC007 (following Dose Escalation Data Review of previous cohorts data) on one occasion on Day 1. The remaining 2 participants will receive matching placebo.
Drug: RXC007
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.

Drug: RXC007 Matching Placebo
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.

Experimental: Part A SAD - Cohort 4
This is the fourth treatment arm in Part A (Single Ascending Dose) of the study. 4 participants will be randomised to receive a selected dose of RXC007 (following Dose Escalation Data Review of previous cohorts data) on one occasion on Day 1. The remaining 2 participants will receive matching placebo.
Drug: RXC007
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.

Drug: RXC007 Matching Placebo
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.

Experimental: Part A SAD - Cohort 5
This is the fifth treatment arm in Part A (Single Ascending Dose) of the study. 4 participants will be randomised to receive a selected dose of RXC007 (following Dose Escalation Data Review of previous cohorts data) on one occasion on Day 1. The remaining 2 participants will receive matching placebo.
Drug: RXC007
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.

Drug: RXC007 Matching Placebo
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.

Experimental: Part A SAD - Cohort 6
This is the sixth treatment arm in Part A (Single Ascending Dose) of the study. 4 participants will be randomised to receive a selected dose of RXC007 (following Dose Escalation Data Review of previous cohorts data) on one occasion on Day 1. The remaining 2 participants will receive matching placebo.
Drug: RXC007
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.

Drug: RXC007 Matching Placebo
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.

Experimental: Part A SAD - Optional Cohort 7
This is an optional seventh treatment arm in Part A (Single Ascending Dose) of the study. If deemed as necessary following Dose Escalation Data Review of previous cohorts data, up to 8 participants may be enrolled into this optional cohort. If enrolled, up to 6 participants will be randomised to receive a selected dose of RXC007 (following Dose Escalation Data Review of previous cohorts data) on one occasion on Day 1. The remaining 2 participants will receive matching placebo.
Drug: RXC007
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.

Drug: RXC007 Matching Placebo
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.

Experimental: Part A SAD - Optional Cohort 8
This is an optional eighth treatment arm in Part A (Single Ascending Dose) of the study. If deemed as necessary following Dose Escalation Data Review of previous cohorts data, up to 8 participants may be enrolled into this optional cohort. If enrolled, up to 6 participants will be randomised to receive a selected dose of RXC007 (following Dose Escalation Data Review of previous cohorts data) on one occasion on Day 1. The remaining 2 participants will receive matching placebo.
Drug: RXC007
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.

Drug: RXC007 Matching Placebo
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.

Experimental: Part B MAD - Cohort 1
This is the first treatment arm in Part B (Multiple Ascending Dose) of the study. 4 participants will be randomised to receive a selected dose of RXC007 (following Dose Escalation Data Review of SAD cohort data) once daily for 14 days. The remaining 2 participants will receive matching placebo.
Drug: RXC007
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.

Drug: RXC007 Matching Placebo
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.

Experimental: Part B MAD - Cohort 2
This is the second treatment arm in Part B (Multiple Ascending Dose) of the study. 4 participants will be randomised to receive a selected dose of RXC007 (following Dose Escalation Data Review of SAD and previous MAD cohort data) once daily for 14 days. The remaining 2 participants will receive matching placebo.
Drug: RXC007
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.

Drug: RXC007 Matching Placebo
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.

Experimental: Part B MAD - Optional Cohort 3
This is an optional third treatment arm in Part B (Multiple Ascending Dose) of the study. If deemed as necessary following Dose Escalation Data Review of previous cohorts data, up to 8 participants may be enrolled into this optional cohort. If enrolled, up to 6 participants will be randomised to receive a selected dose of RXC007 (following Dose Escalation Data Review of previous cohorts data) once daily for 14 days. The remaining 2 participants will receive matching placebo.
Drug: RXC007
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.

Drug: RXC007 Matching Placebo
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.

Experimental: Part B MAD - Optional Cohort 4
This is an optional fourth treatment arm in Part B (Multiple Ascending Dose) of the study. If deemed as necessary following Dose Escalation Data Review of previous cohorts data, up to 8 participants may be enrolled into this optional cohort. If enrolled, up to 6 participants will be randomised to receive a selected dose of RXC007 (following Dose Escalation Data Review of previous cohorts data) once daily for 14 days. The remaining 2 participants will receive matching placebo.
Drug: RXC007
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.

Drug: RXC007 Matching Placebo
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.




Primary Outcome Measures :
  1. Treatment Emergent Adverse Events [ Time Frame: Collection of TEAEs occurs through ad hoc reporting from the participants from the point of first dose administration (Day 1 in each part) through to study completion (up to 6 weeks for Part A & 8 weeks for Part B). ]
    This primary endpoint relates to the number of participants who report a treatment emergent adverse event (TEAEs) across all study parts.

  2. Number of participants who report a change from normal range values for laboratory safety parameters (serum biochemistry, serum haematology or urinalysis) from first dose on Day 1 to post-study follow up visit. [ Time Frame: Part A: From Day 1 to post-study follow up visit (up to 6 weeks) & Part B: From Day 1 to post-study follow up visit (up to 8 weeks) ]
    This primary endpoint will report the number of participants within each cohort of Part A and Part B of the study who record a value which is deemed as outside of the normal range (regardless of clinical significance) for any of the serum biochemistry, serum haematology or urinalysis parameters as defined in the study protocol following first dose administration on Day 1 up to completion of the post-study visit.

  3. Number of participants who report a change from normal range values for vital signs parameters (blood pressure, pulse rate, respiration rate, oral body temperature) from first dose on Day 1 to post-study follow up visit. [ Time Frame: Part A: From Day 1 to post-study follow up visit (up to 6 weeks) & Part B: From Day 1 to post-study follow up visit (up to 8 weeks) ]
    This primary endpoint will report the number of participants within each cohort of Part A and Part B of the study who record a value which is deemed as outside of the normal range (regardless of clinical significance) for any of the vital signs parameters (systolic/diastolic blood pressure, pulse rate, respiration rate, oral body temperature) as defined in the study protocol following first dose administration on Day 1 up to completion of the post-study visit.

  4. Number of participants who report a change from normal range values for any of the associated 12-Lead ECG parameters (heart rate, PR interval, QRS width, QT interval and QTcF interval) from first dose on Day 1 to post-study follow up visit. [ Time Frame: Part A: From Day 1 to post-study follow up visit (up to 6 weeks) & Part B: From Day 1 to post-study follow up visit (up to 8 weeks) ]
    This primary endpoint will report the number of participants within each cohort of Part A and Part B of the study who record a value which is deemed as outside of the normal range (regardless of clinical significance) for any of the 12-Lead ECG parameters (heart rate, PR interval, QRS width, QT interval and QTcF interval) as defined in the study protocol following first dose administration on Day 1 up to completion of the post-study visit.


Secondary Outcome Measures :
  1. Pharmacokinetic Parameters - Part A - Maximum observed concentration (Cmax) [ Time Frame: Plasma samples for Cmax evaluation of RXC007 in Part A: Day 1 pre-dose, 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, 48 hr, 72 hr post-dose & post-study follow up (up to 6 weeks for Part A). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the maximum observed concentration (Cmax) of RXC007 in plasma for Part A cohorts.

  2. Pharmacokinetic Parameters - Part A - Time to maximum observed concentration (Tmax) [ Time Frame: Plasma samples for Tmax evaluation of RXC007 in Part A: Day 1 pre-dose, 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, 48 hr, 72 hr post-dose & post-study follow up (up to 6 weeks for Part A). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the time to maximum observed concentration (Tmax) of RXC007 in plasma for Part A cohorts.

  3. Pharmacokinetic Parameters - Part A - Elimination rate constant (λz) [ Time Frame: Plasma samples for λz evaluation of RXC007 in Part A: Day 1 pre-dose, 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, 48 hr, 72 hr post-dose & post-study follow up (up to 6 weeks for Part A). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the elimination rate constant (λz) of RXC007 in plasma for Part A cohorts.

  4. Pharmacokinetic Parameters - Part A - Terminal elimination half-life (t1/2) [ Time Frame: Plasma samples for t1/2 evaluation of RXC007 in Part A: Day 1 pre-dose, 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, 48 hr, 72 hr post-dose & post-study follow up (up to 6 weeks for Part A). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the terminal elimination half-life (t1/2) of RXC007 in plasma for Part A cohorts.

  5. Pharmacokinetic Parameters - Part A - Area under the concentration-time curve (AUC) from the time of dosing to the time of the last measurable concentration (AUC0-t) [ Time Frame: Plasma samples for AUC0-t evaluation of RXC007 in Part A: Day 1 pre-dose, 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, 48 hr, 72 hr post-dose & post-study follow up (up to 6 weeks for Part A). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the area under the concentration-time curve (AUC) from the time of dosing to the time of the last measurable concentration (AUC0-t) of RXC007 in plasma for Part A cohorts.

  6. Pharmacokinetic Parameters - Part A - Area under the concentration-time curve (AUC) extrapolated to infinity (AUC0-inf) [ Time Frame: Plasma samples for AUC0-inf evaluation of RXC007 in Part A: Day 1 pre-dose, 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, 48 hr, 72 hr post-dose & post-study follow up (up to 6 weeks for Part A). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the area under the concentration-time curve (AUC) extrapolated to infinity (AUC0-inf) of RXC007 in plasma for Part A cohorts.

  7. Pharmacokinetic Parameters - Part A - Residual Area (AUC%extrapolated) [ Time Frame: Plasma samples for AUC%extrapolated evaluation of RXC007 in Part A: Day 1 pre-dose, 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, 48 hr, 72 hr post-dose & post-study follow up (up to 6 weeks for Part A). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the residual area (AUC%extrapolated) of RXC007 in plasma for Part A cohorts.

  8. Pharmacokinetic Parameters - Part A - Total apparent clearance following extravascular administration (CL/F) [ Time Frame: Plasma samples for CL/F evaluation of RXC007 in Part A: Day 1 pre-dose, 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, 48 hr, 72 hr post-dose & post-study follow up (up to 6 weeks for Part A). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the total apparent clearance following extravascular administration (CL/F) of RXC007 in plasma for Part A cohorts.

  9. Pharmacokinetic Parameters - Part A - Apparent volume of distribution following extravascular administration (Vz/F) [ Time Frame: Plasma samples for Vz/F evaluation of RXC007 in Part A: Day 1 pre-dose, 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, 48 hr, 72 hr post-dose & post-study follow up (up to 6 weeks for Part A). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the apparent volume of distribution following extravascular administration (Vz/F) of RXC007 in plasma for Part A cohorts.

  10. Pharmacokinetic Parameters - Part B - Maximum observed concentration (Cmax) [ Time Frame: Plasma samples for Cmax evaluation of RXC007 in Part B: Day 1 & 14: 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr post-dose, Day 7, Day 16: 48 hr post-Day 14 dose & Day 17: 72 hr post-Day 14 dose (up to 8 weeks for Part B). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the maximum observed concentration (Cmax) of RXC007 in plasma for Part B cohorts.

  11. Pharmacokinetic Parameters - Part B - Time to maximum observed concentration (Tmax) [ Time Frame: Plasma samples for Tmax evaluation of RXC007 in Part B: Day 1 & 14: 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr post-dose, Day 7, Day 16: 48 hr post-Day 14 dose & Day 17: 72 hr post-Day 14 dose (up to 8 weeks for Part B). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the time to maximum observed concentration (Tmax) of RXC007 in plasma for Part B cohorts.

  12. Pharmacokinetic Parameters - Part B - Elimination rate constant (λz) [ Time Frame: Plasma samples for λz evaluation of RXC007 in Part B: Day 1 & 14: 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr post-dose, Day 7, Day 16: 48 hr post-Day 14 dose & Day 17: 72 hr post-Day 14 dose (up to 8 weeks for Part B). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the elimination rate constant (λz) of RXC007 in plasma for Part B cohorts.

  13. Pharmacokinetic Parameters - Part B - Terminal elimination half-life (t1/2) [ Time Frame: Plasma samples for t1/2 evaluation of RXC007 in Part B: Day 1 & 14: 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr post-dose, Day 7, Day 16: 48 hr post-Day 14 dose & Day 17: 72 hr post-Day 14 dose (up to 8 weeks for Part B). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the terminal elimination half-life (t1/2) of RXC007 in plasma for Part B cohorts.

  14. Pharmacokinetic Parameters - Part B - Area under the concentration-time curve (AUC) from 0 to τ, where τ is the dosing interval (0 - 24 h) (AUC0-τ) [ Time Frame: Plasma samples for AUC0-τ evaluation of RXC007 in Part B: Day 1 & 14: 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr post-dose, Day 7, Day 16: 48 hr post-Day 14 dose & Day 17: 72 hr post-Day 14 dose (up to 8 weeks for Part B). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the area under the concentration-time curve (AUC) from 0 to τ, where τ is the dosing interval (0 - 24 h) (AUC0-τ) of RXC007 in plasma for Part B cohorts.

  15. Pharmacokinetic Parameters - Part B - Area under the concentration-time curve (AUC) from the time of dosing to the time of the last measurable concentration (AUC0-t) [ Time Frame: Plasma samples for AUC0-t evaluation of RXC007 in Part B: Day 1 & 14: 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr post-dose, Day 7, Day 16: 48 hr post-Day 14 dose & Day 17: 72 hr post-Day 14 dose (up to 8 weeks for Part B). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the area under the concentration-time curve (AUC) from the time of dosing to the time of the last measurable concentration (AUC0-t) of RXC007 in plasma for Part B cohorts.

  16. Pharmacokinetic Parameters - Part B - Area under the concentration-time curve (AUC) extrapolated to infinity (AUC0-inf) [ Time Frame: Plasma samples for AUC0-inf evaluation of RXC007 in Part B: Day 1 & 14: 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr post-dose, Day 7, Day 16: 48 hr post-Day 14 dose & Day 17: 72 hr post-Day 14 dose (up to 8 weeks for Part B). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the area under the concentration-time curve (AUC) extrapolated to infinity (AUC0-inf) of RXC007 in plasma for Part B cohorts.

  17. Pharmacokinetic Parameters - Part B - Residual area (AUC%extrapolated) [ Time Frame: Plasma samples for AUC%extrapolated evaluation of RXC007 in Part B: Day 1 & 14: 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr post-dose, Day 7, Day 16: 48 hr post-Day 14 dose & Day 17: 72 hr post-Day 14 dose (up to 8 weeks for Part B). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the residual area (AUC%extrapolated) of RXC007 in plasma for Part B cohorts.

  18. Pharmacokinetic Parameters - Part B - Accumulation ratio calculated from Cmax (ARCmax) [ Time Frame: Plasma samples for ARCmax evaluation of RXC007 in Part B: Day 1 & 14: 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr post-dose, Day 7, Day 16: 48 hr post-Day 14 dose & Day 17: 72 hr post-Day 14 dose (up to 8 weeks for Part B). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the accumulation ratio calculated from Cmax (ARCmax) of RXC007 in plasma for Part B cohorts.

  19. Pharmacokinetic Parameters - Part B - Accumulation ratio calculated from AUC (ARAUC) [ Time Frame: Plasma samples for ARAUC evaluation of RXC007 in Part B: Day 1 & 14: 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr post-dose, Day 7, Day 16: 48 hr post-Day 14 dose & Day 17: 72 hr post-Day 14 dose (up to 8 weeks for Part B). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the accumulation ratio calculated from AUC (ARAUC) of RXC007 in plasma for Part B cohorts.

  20. Pharmacokinetic Parameters - Part B - Total apparent clearance following extravascular administration (CL/F) [ Time Frame: Plasma samples for CL/F evaluation of RXC007 in Part B: Day 1 & 14: 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr post-dose, Day 7, Day 16: 48 hr post-Day 14 dose & Day 17: 72 hr post-Day 14 dose (up to 8 weeks for Part B). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the total apparent clearance following extravascular administration (CL/F) of RXC007 in plasma for Part B cohorts.

  21. Pharmacokinetic Parameters - Part B - Apparent volume of distribution following extravascular administration (Vz/F) [ Time Frame: Plasma samples for Vz/F evaluation of RXC007 in Part B: Day 1 & 14: 15 mins, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr post-dose, Day 7, Day 16: 48 hr post-Day 14 dose & Day 17: 72 hr post-Day 14 dose (up to 8 weeks for Part B). ]
    Plasma samples will be obtained in order to evaluate defined plasma pharmacokinetic parameters for RXC007. This endpoint will report the summary of derived pharmacokinetic parameters for the apparent volume of distribution following extravascular administration (Vz/F) of RXC007 in plasma for Part B cohorts.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   As this is a first-in-human (FiH) study, as per the EMA guidance for risk mitigation in FiH studies, the most relevant population is healthy male volunteers.
Accepts Healthy Volunteers:   Yes
Criteria

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.
  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 or any of the excipients contained within the IMP.
  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.
  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.
  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 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) / pulse rate, respiration rate, oral temperature) determined within 28 days before first dose of IMP.
  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 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, 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.
  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. (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.
  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 first dose administration with the study medication 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04931147


Contacts
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Contact: Helen McKeever +44 (0) 7788278783 h.mckeever@redxpharma.com
Contact: Emma McMurtry +44 (0) 79682 34694 e.mcmurtry@redxpharma.com

Locations
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United Kingdom
Simbec-Orion Clinical Pharmacology Recruiting
Merthyr Tydfil, Mid Glamorgan, United Kingdom, CF48 4DR
Contact: Annelize Koch, MBChB;FFPM    +441443 690977    annelize.koch@simbecorion.com   
Sponsors and Collaborators
Redx Pharma Plc
Simbec Research
Investigators
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Principal Investigator: Annelize Koch Simbec-Orion Clinical Pharmacology
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Responsible Party: Redx Pharma Plc
ClinicalTrials.gov Identifier: NCT04931147    
Other Study ID Numbers: RXC007/0001
First Posted: June 18, 2021    Key Record Dates
Last Update Posted: June 18, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: At this stage, it is not planned that any IPD information will be shared with other researchers outside of the Sponsor and Clinical Research Organisation undertaking the conduct of this study.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Kidney Diseases
Fibrosis
Inflammation
Pathologic Processes
Urologic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases