Safety, Tolerability, Pharmacokinetics, and Food Effect Study of RV299 in Healthy Adults (NCT06033612) | Clinical Trial Compass
CompletedPhase 1
Safety, Tolerability, Pharmacokinetics, and Food Effect Study of RV299 in Healthy Adults
United Kingdom50 participantsStarted 2021-11-12
Plain-language summary
The main aims of the study are to assess the safety, tolerability, pharmacokinetics and food effects of RV299 compared to Placebo in healthy adult participants.
The study consists of three parts: single ascending dose (Part A), multiple ascending doses (Part B) and food effect (Part C) in Caucasian participants.
Who can participate
Age range20 Years – 40 Years
SexALL
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Inclusion criteria
✓. Male or Female, Caucasian, aged greater than or equal to 20 to less than or equal to 40 years at the date of signing informed consent.
✓. Participants in Caucasian cohorts should be distinguished by very light to brown skin pigmentation and straight to wavy or curly hair, and should be indigenous to Europe, northern Africa, western Asia, India. This includes Caucasian participants from North America, Australia and South Africa.
✓. Healthy as defined by: a) the absence of clinically significant illness and surgery within four weeks prior to dosing; b) the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, haematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
✓. Participants must agree to use contraceptive requirements as described in the study protocol for the applicable duration.
✓. Participants must agree not to donate sperm or ova from the time of the first administration of trial medication until 3 months after three months after the last follow-up visit.
✓. Participants must have a body mass index (BMI) between 18.0-25.0 kg/m² inclusive at screening.
✓. Satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluation that is reasonably likely to interfere with the participant's participation in or ability to complete the trial as assessed by the Investigator.
✓. Ability to provide written, personally signed, and dated informed consent.
Exclusion criteria
What they're measuring
1
Number of participants with treatment-emergent adverse events (TEAE) as assessed by CTCAE V5.0.
Timeframe: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
2
Evaluate the proportion of participants with clinically significant shifts in haematology/clinical chemistry/coagulation/urinalysis values from baseline following dosing with RV299
Timeframe: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
3
Evaluate the proportion of subjects with changes in ECG measurements from baseline following dosing with RV299
Timeframe: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
4
Evaluate safety and tolerability of RV299 by assessing changes from baseline in tympanic temperature (vital sign parameters)
Timeframe: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
5
Evaluate safety and tolerability of RV299 by assessing changes from baseline in blood pressure (BP) (vital sign parameters).
Timeframe: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
6
Evaluate safety and tolerability of RV299 by assessing changes from baseline in heart rate (HR) (vital sign parameters).
Timeframe: PPart A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
✕. Current or recurrent disease (e.g., cardiovascular, haematological, neurological, endocrine, immunological, renal, hepatic or gastrointestinal or other conditions) that could affect the action, absorption, or disposition of RV299, or could affect clinical assessments or clinical laboratory evaluations.
✕. Current or relevant history of physical or psychiatric illness that are not stable or may require a change in treatment, use of prohibited therapies during the trial or make the participant unlikely to fully comply with the requirements of the trial or complete the trial, or any condition that presents undue risk from the investigational product or trial procedures.
✕. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial may influence the result of the trial, or the participant's ability to participate in the trial.
✕. Use or intention to use any medications/products that are known inhibitors of the CYP3A4 enzymes or substrates of Aldehyde oxidase (AO), Pglycoprotein (PgP) or Breast Cancer Resistance Protein (BCRP) for 2 weeks prior to Day 1 of the dosing period up to the follow-up visit. (The Indiana University (2016) "Cytochrome P450 Drug Interaction Table" should be utilized to determine inhibitors of CYP3A) (http://medicine.iupui.edu/clinpharm/ddis/table.aspx).
✕. The history or presence of any of the following cardiac conditions known structural cardiac abnormalities; family history of long QT syndrome; cardiac syncope or recurrent, idiopathic syncope; exercise related clinically significant cardiac events.
✕. Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG or clinically important abnormalities that may interfere with the interpretation of QTc interval changes. (Participants with borderline abnormalities may be included if the deviations do not pose a safety risk, and if agreed between the appointed Cardiologist and the PI.)
✕. Has vital signs outside of the following normal range at screening or Day -1/Day-2.
✕. Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening;
7
Evaluate safety and tolerability of RV299 by assessing changes from baseline in respiratory rate (vital sign parameters).
Timeframe: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
8
Assess area under the plasma concentration versus time curve (AUC) of midazolam (as index substrate) from 0 to 24 hours post-dose (AUC0-24h) before and after dosing with RV299.
Timeframe: Part B Cohort 3 only: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 13, 16, and 24 hours following administration of midazolam on Day 1 and Day 7.
9
Assess time to maximum plasma concentration (tmax) of midazolam (as index substrate) before and after dosing with RV299.
Timeframe: Part B Cohort 3 only: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 13, 16, and 24 hours following administration of midazolam on Day 1 and Day 7.
10
Assess terminal half life of (t1/2) of midazolam (as index substrate) before and after dosing with RV299.
Timeframe: Part B Cohort 3 only: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 13, 16, and 24 hours following administration of midazolam on Day 1 and Day 7.
11
Assess maximum plasma concentration (Cmax) of midazolam (as index substrate) before and after dosing with RV299.
Timeframe: Part B Cohort 3 only: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 13, 16, and 24 hours following administration of midazolam on Day 1 and Day 7.