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

NCT04931147 | Completed Phase 1

• 1 other identifier: RXC007/0001
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Fibrosis; Inflammation; Idiopathic Pulmonary Fibrosis; Non-alcoholic Steatohepatitis; Liver Diseases; Kidney Diseases

Outcome Measures

Primary Outcomes (4)

• Treatment Emergent Adverse Events

  This primary endpoint relates to the number of participants who report a treatment emergent adverse event (TEAEs) across all study parts.

  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 & up to 8 weeks for Part B & C).

• 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.

  This primary endpoint will report the number of participants within each cohort of Part A, Part B \& Part C 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.

  Part A: From Day 1 to post-study follow up visit (up to 6 weeks) & Part B/C: From Day 1 to post-study follow up visit (up to 8 weeks)

• 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.

  This primary endpoint will report the number of participants within each cohort of Part A, Part B \& Part C 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.

  Part A: From Day 1 to post-study follow up visit (up to 6 weeks) & Part B/C: From Day 1 to post-study follow up visit (up to 8 weeks)

• 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.

  This primary endpoint will report the number of participants within each cohort of Part A, Part B \& Part C 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.

  Part A: From Day 1 to post-study follow up visit (up to 6 weeks) & Part B/C: From Day 1 to post-study follow up visit (up to 8 weeks)

Secondary Outcomes (30)

• Pharmacokinetic Parameters - Part A - Maximum observed concentration (Cmax)

  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).

• Pharmacokinetic Parameters - Part A - Time to maximum observed concentration (Tmax)

  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).

• Pharmacokinetic Parameters - Part A - Elimination rate constant (λz)

  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).

• Pharmacokinetic Parameters - Part A - Terminal elimination half-life (t1/2)

  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).

• 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)

  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).

Study Arms (18)

Part A SAD - Cohort 1

EXPERIMENTAL

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; Drug: RXC007 Matching Placebo

Part A SAD - Cohort 2

EXPERIMENTAL

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; Drug: RXC007 Matching Placebo

Part A SAD - Cohort 3

EXPERIMENTAL

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; Drug: RXC007 Matching Placebo

Part A SAD - Cohort 4

EXPERIMENTAL

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; Drug: RXC007 Matching Placebo

Part A SAD - Cohort 5

EXPERIMENTAL

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; Drug: RXC007 Matching Placebo

Part A SAD - Cohort 6

EXPERIMENTAL

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; Drug: RXC007 Matching Placebo

Part A SAD - Optional Cohort 7

EXPERIMENTAL

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; Drug: RXC007 Matching Placebo

Part A SAD - Optional Cohort 8

EXPERIMENTAL

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; Drug: RXC007 Matching Placebo

Part B MAD - Cohort 1

EXPERIMENTAL

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; Drug: RXC007 Matching Placebo

Part B MAD - Cohort 2

EXPERIMENTAL

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; Drug: RXC007 Matching Placebo

Part B MAD - Optional Cohort 3

EXPERIMENTAL

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; Drug: RXC007 Matching Placebo

Part B MAD - Optional Cohort 4

EXPERIMENTAL

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; Drug: RXC007 Matching Placebo

Part A SAD - Optional Cohort 9

EXPERIMENTAL

This is an optional ninth 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; Drug: RXC007 Matching Placebo

Part A SAD - Optional Cohort 10

EXPERIMENTAL

This is an optional tenth 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; Drug: RXC007 Matching Placebo

Part B MAD - Optional Cohort 5

EXPERIMENTAL

This is an optional fifth 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; Drug: RXC007 Matching Placebo

Part B MAD - Optional Cohort 6

EXPERIMENTAL

This is an optional sixth 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; Drug: RXC007 Matching Placebo

Part C DDI - Cohort 1 Rosuvastatin

EXPERIMENTAL

This is the first treatment arm in Part C (Drug-Drug Interaction) of the study. All participants within the cohort (12 participants) will to receive a selected dose of RXC007 (following Dose Escalation Data Review from Part A and Part B) and 10 mg rosuvastatin as follows: single dose of rosuvastatin (10 milligrams) on Day 1 followed by three single doses of RXC007 on Day 6, Day 7 \& Day 8 before taking a single dose of both RXC007 and rosuvastatin together on Day 9.

Drug: RXC007

Part C DDI - Cohort 2 Metformin

EXPERIMENTAL

This is the second treatment arm in Part C (Drug-Drug Interaction) of the study. All participants within the cohort (12 participants) will to receive a selected dose of RXC007 (following Dose Escalation Data Review from Part A and Part B) and 500 mg metformin as follows: single dose of metformin (500 milligrams) on Day 1 followed by three single doses of RXC007 on Day 4, Day 5 \& Day 6 before taking a single dose of both RXC007 and metformin together on Day 7.

Drug: RXC007

Interventions

RXC007 DRUG

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.

Part A SAD - Cohort 1; Part A SAD - Cohort 2; Part A SAD - Cohort 3; Part A SAD - Cohort 4; Part A SAD - Cohort 5; Part A SAD - Cohort 6; Part A SAD - Optional Cohort 10; Part A SAD - Optional Cohort 7; Part A SAD - Optional Cohort 8; Part A SAD - Optional Cohort 9; Part B MAD - Cohort 1; Part B MAD - Cohort 2; Part B MAD - Optional Cohort 3; Part B MAD - Optional Cohort 4; Part B MAD - Optional Cohort 5; Part B MAD - Optional Cohort 6; Part C DDI - Cohort 1 Rosuvastatin; Part C DDI - Cohort 2 Metformin

RXC007 Matching Placebo DRUG

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.

Part A SAD - Cohort 1; Part A SAD - Cohort 2; Part A SAD - Cohort 3; Part A SAD - Cohort 4; Part A SAD - Cohort 5; Part A SAD - Cohort 6; Part A SAD - Optional Cohort 10; Part A SAD - Optional Cohort 7; Part A SAD - Optional Cohort 8; Part A SAD - Optional Cohort 9; Part B MAD - Cohort 1; Part B MAD - Cohort 2; Part B MAD - Optional Cohort 3; Part B MAD - Optional Cohort 4; Part B MAD - Optional Cohort 5; Part B MAD - Optional Cohort 6

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: 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.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male participants, between 18 and 55 years of age, inclusive.
• 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.
• Participant with a body mass index (BMI) of 18.0-32.0 kg/m2.
• Participant with a body weight of 60 kg or greater.
• No clinically significant history of previous allergy / sensitivity to RXC007, rosuvastatin or metformin, or any of the excipients contained within the IMP/NIMP.
• 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.
• Haemoglobin and haematocrit above the lower limit of the normal range for the reference laboratory.
• Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) \< 1.5 times the upper limit of the normal (ULN) range for the reference laboratory.
• 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).
• Participant with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCV Ab) test results at Screening.
• 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.
• 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.
• Participant must be available to complete the study (including all follow-up visits).
• Participant must satisfy an Investigator about his fitness to participate in the study.
• Participant must provide written informed consent to participate in the study.

You may not qualify if:

• A clinically significant history of gastrointestinal disorder likely to influence IMP/NIMP absorption.
• A clinically significant history of infection in the last 3 months.
• 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.
• Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
• 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).
• Participant with a glomerular filtration rate less than 80 mL/min/1.73m2 (calculated by Cockcroft-Gault equation.
• 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.
• Inability to communicate well with the Investigators (i.e., language problem, poor mental development or impaired cerebral function).
• 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).
• Donation of 450 mL or more blood within the 3 months before the first dose of IMP/NIMP.
• 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.
• 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).
• Participants who have received a COVID-19 vaccine injection within 28 days prior to the first dose of IMP/NIMP.

Sponsors & Collaborators

• Redx Pharma Ltd: lead
• Simbec Research: collaborator

Study Sites (1)

Simbec-Orion Clinical Pharmacology

Merthyr Tydfil, Mid Glamorgan, CF48 4DR, United Kingdom

Location

MeSH Terms

Conditions

Fibrosis; Inflammation; Idiopathic Pulmonary Fibrosis; Non-alcoholic Fatty Liver Disease; Liver Diseases; Kidney Diseases

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Fatty Liver; Digestive System Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Annelize Koch

  Simbec-Orion Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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. Part C of the study will assume an open-label design whereby all participants will receive active RXC007. 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 4, 2021
• First Posted: June 18, 2021
• Study Start: May 13, 2021
• Primary Completion: March 8, 2023
• Study Completion: March 8, 2023
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)