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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of RXC007.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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/m
- •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.
- •Participants with a negative COVID-19 reverse transcription polymerase chain reaction (RT-PCR) test on admission (if required).
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: RXC007 (Drug)
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.
干预措施: RXC007 Matching Placebo (Drug)
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.
干预措施: RXC007 (Drug)
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.
干预措施: RXC007 Matching Placebo (Drug)
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.
干预措施: RXC007 (Drug)
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.
干预措施: RXC007 Matching Placebo (Drug)
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.
干预措施: RXC007 (Drug)
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.
干预措施: RXC007 Matching Placebo (Drug)
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.
干预措施: RXC007 (Drug)
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.
干预措施: RXC007 Matching Placebo (Drug)
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.
干预措施: RXC007 (Drug)
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.
干预措施: RXC007 Matching Placebo (Drug)
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.
干预措施: RXC007 (Drug)
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.
干预措施: RXC007 Matching Placebo (Drug)
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.
干预措施: RXC007 (Drug)
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.
干预措施: RXC007 Matching Placebo (Drug)
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.
干预措施: RXC007 (Drug)
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.
干预措施: RXC007 Matching Placebo (Drug)
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.
干预措施: RXC007 (Drug)
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.
干预措施: RXC007 Matching Placebo (Drug)
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.
干预措施: RXC007 (Drug)
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.
干预措施: RXC007 Matching Placebo (Drug)
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.
干预措施: RXC007 (Drug)
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.
干预措施: RXC007 Matching Placebo (Drug)
Part A SAD - Optional Cohort 9
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.
干预措施: RXC007 (Drug)
Part A SAD - Optional Cohort 9
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.
干预措施: RXC007 Matching Placebo (Drug)
Part A SAD - Optional Cohort 10
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.
干预措施: RXC007 (Drug)
Part A SAD - Optional Cohort 10
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.
干预措施: RXC007 Matching Placebo (Drug)
Part B MAD - Optional Cohort 5
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.
干预措施: RXC007 (Drug)
Part B MAD - Optional Cohort 5
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.
干预措施: RXC007 Matching Placebo (Drug)
Part B MAD - Optional Cohort 6
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.
干预措施: RXC007 (Drug)
Part B MAD - Optional Cohort 6
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.
干预措施: RXC007 Matching Placebo (Drug)
Part C DDI - Cohort 1 Rosuvastatin
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.
干预措施: RXC007 (Drug)
Part C DDI - Cohort 2 Metformin
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.
干预措施: RXC007 (Drug)
结局指标
主要结局
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.
时间窗: 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)
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.
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.
时间窗: 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)
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.
Treatment Emergent Adverse Events
时间窗: 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).
This primary endpoint relates to the number of participants who report a treatment emergent adverse event (TEAEs) across all study parts.
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.
时间窗: 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)
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.
次要结局
- 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 - 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).)
- 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 - Residual Area (AUC%extrapolated)(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).)
- Pharmacokinetic Parameters - Part B - Time to maximum observed concentration (Tmax)(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).)
- Pharmacokinetic Parameters - Part B - Elimination rate constant (λz)(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).)
- Pharmacokinetic Parameters - Part B - Area under the concentration-time curve (AUC) extrapolated to infinity (AUC0-inf)(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).)
- Pharmacokinetic Parameters - Part B - Accumulation ratio calculated from Cmax (ARCmax)(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).)
- Pharmacokinetic Parameters - Part B - Total apparent clearance following extravascular administration (CL/F)(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).)
- 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) extrapolated to infinity (AUC0-inf)(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).)
- Pharmacokinetic Parameters - Part A - Total apparent clearance following extravascular administration (CL/F)(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).)
- Pharmacokinetic Parameters - Part A - Apparent volume of distribution following extravascular administration (Vz/F)(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).)
- Pharmacokinetic Parameters - Part B - Maximum observed concentration (Cmax)(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).)
- 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)(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).)
- 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)(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).)
- Pharmacokinetic Parameters - Part B - Residual area (AUC%extrapolated)(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).)
- Pharmacokinetic Parameters - Part C - Time to maximum observed concentration (Tmax)(Plasma samples for Tmax evaluation of in Part C: Maximum of 34 samples in Cohort 1 from Day 1 pre-dose to Day 13 and maximum of 33 samples in Cohort 2 from Day 1 pre-dose to Day 10)
- Pharmacokinetic Parameters - Part B - Terminal elimination half-life (t1/2)(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).)
- Pharmacokinetic Parameters - Part B - Accumulation ratio calculated from AUC (ARAUC)(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).)
- Pharmacokinetic Parameters - Part B - Apparent volume of distribution following extravascular administration (Vz/F)(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).)
- Pharmacokinetic Parameters - Part C - Maximum observed concentration (Cmax)(Plasma samples for Cmax evaluation of in Part C: Maximum of 34 samples in Cohort 1 from Day 1 pre-dose to Day 13 and maximum of 33 samples in Cohort 2 from Day 1 pre-dose to Day 10)
- Pharmacokinetic Parameters - Part C - Elimination rate constant (λz)(Plasma samples for λz evaluation of in Part C: Maximum of 34 samples in Cohort 1 from Day 1 pre-dose to Day 13 and maximum of 33 samples in Cohort 2 from Day 1 pre-dose to Day 10)
- Pharmacokinetic Parameters - Part C - Terminal elimination half-life (t1/2)(Plasma samples for t1/2 evaluation of in Part C: Maximum of 34 samples in Cohort 1 from Day 1 pre-dose to Day 13 and maximum of 33 samples in Cohort 2 from Day 1 pre-dose to Day 10)
- Pharmacokinetic Parameters - Part C - 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 in Part C: Maximum of 34 samples in Cohort 1 from Day 1 pre-dose to Day 13 and maximum of 33 samples in Cohort 2 from Day 1 pre-dose to Day 10)
- Pharmacokinetic Parameters - Part C - Total apparent clearance following extravascular administration (CL/F)(Plasma samples for CL/F evaluation of in Part C: Maximum of 34 samples in Cohort 1 from Day 1 pre-dose to Day 13 and maximum of 33 samples in Cohort 2 from Day 1 pre-dose to Day 10)
- Pharmacokinetic Parameters - Part C - Area under the concentration-time curve (AUC) extrapolated to infinity (AUC0-inf)(Plasma samples for AUC0-inf evaluation of in Part C: Maximum of 34 samples in Cohort 1 from Day 1 pre-dose to Day 13 and maximum of 33 samples in Cohort 2 from Day 1 pre-dose to Day 10)
- Pharmacokinetic Parameters - Part C - Residual area (AUC%extrapolated)(Plasma samples for AUC%extrapolated evaluation of in Part C: Maximum of 34 samples in Cohort 1 from Day 1 pre-dose to Day 13 and maximum of 33 samples in Cohort 2 from Day 1 pre-dose to Day 10)
- Pharmacokinetic Parameters - Part C - Apparent volume of distribution following extravascular administration (Vz/F)(Plasma samples for Vz/F evaluation of in Part C: Maximum of 34 samples in Cohort 1 from Day 1 pre-dose to Day 13 and maximum of 33 samples in Cohort 2 from Day 1 pre-dose to Day 10)