Safety, Tolerability, Pharmacokinetics, and Food Effect Study of RV299 in Healthy Adults

NCT06033612 | Completed Phase 1

• 2 other identifiers: REVD001C5251001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Respiratory Syncytial Virus Infections

Keywords

RSV; bronchiolitis; lower respiratory tract infection; LRTI

Outcome Measures

Primary Outcomes (11)

• Number of participants with treatment-emergent adverse events (TEAE) as assessed by CTCAE V5.0.

  Listings and summary tables of AEs will be based on TEAEs (defined as events starting, or worsening, after the first dose of RV299).

  Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose

• Evaluate the proportion of participants with clinically significant shifts in haematology/clinical chemistry/coagulation/urinalysis values from baseline following dosing with RV299

  Blood and urine tests will be conducted at a central laboratory. Results at each visit will be summarized using the statistics n, mean, standard deviation, median, minimum and maximum.

  Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose

• Evaluate the proportion of subjects with changes in ECG measurements from baseline following dosing with RV299

  Parameters collected will be: PR interval (msec); QRS interval (msec); QT interval (msec); QTcB interval (msec); QTcF interval (msec); Heart rate (bpm). Results at each visit will be summarized using the statistics n, mean, standard deviation, median, minimum and maximum.

  Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose

• Evaluate safety and tolerability of RV299 by assessing changes from baseline in tympanic temperature (vital sign parameters)

  Tympanic temperature will be collected in degrees Celsius (°C). Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.

  Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose

• Evaluate safety and tolerability of RV299 by assessing changes from baseline in blood pressure (BP) (vital sign parameters).

  Blood pressure (systolic and diastolic) will be measure in mm Hg. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.

  Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose

• Evaluate safety and tolerability of RV299 by assessing changes from baseline in heart rate (HR) (vital sign parameters).

  Heart rate will be measure in beats per minute (bpm). Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.

  PPart A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose

• Evaluate safety and tolerability of RV299 by assessing changes from baseline in respiratory rate (vital sign parameters).

  Respiratory rate will be measured in breaths per minute. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.

  Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose

• 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.

  Pharmacokinetic analysis will include listings and summaries of midazolam concentration by time point and analysis of relationship with dose and body weight.

  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.

• Assess time to maximum plasma concentration (tmax) of midazolam (as index substrate) before and after dosing with RV299.

  Pharmacokinetic analysis will include listings and summaries of midazolam concentration by time point and analysis of relationship with dose and body weight

  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.

• Assess terminal half life of (t1/2) of midazolam (as index substrate) before and after dosing with RV299.

  Pharmacokinetic analysis will include listings and summaries of midazolam concentration by time point and analysis of relationship with dose and body weight

  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.

• Assess maximum plasma concentration (Cmax) of midazolam (as index substrate) before and after dosing with RV299.

  Pharmacokinetic analysis will include listings and summaries of midazolam concentration by time point and analysis of relationship with dose and body weight

  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.

Secondary Outcomes (15)

• Characterise plasma pharmacokinetics (PK) of RV299 by assessing time to maximum plasma concentration (tmax) following single and multiple doses of RV299.

  Parts A, B and C: pre-dose (Day 1) to 7 days after final dose of RV299

• Assess terminal half-life (t1/2) of RV299 following single and multiple doses of RV299.

  Parts A, B and C: pre-dose (Day 1) to 7 days after final dose of RV299

• Assess rate constant (λz) of RV299 following single and multiple doses of RV299.

  Parts A, B and C: pre-dose (Day 1) to 7 days after final dose of RV299

• Assess maximum plasma concentration (Cmax) of RV299 following single and multiple doses of RV299.

  Parts A, B and C: pre-dose (Day 1) to 7 days after final dose of RV299

• Assess area under the plasma concentration versus time curve (AUC) of RV299 from time zero to last quantifiable plasma concentration (AUC0-t) following single and multiple doses of RV299.

  Parts A, B and C: pre-dose (Day 1) to 7 days after final dose of RV299

Study Arms (3)

Part A Single Ascending Dose (SAD) - RV299/Placebo

EXPERIMENTAL

Participants will receive RV299 or placebo as a single dose on Day 1. Sentinel dosing will be used (one on RV299 and one on placebo) before the rest of the cohort are dosed together.

Drug: RV299; Drug: Placebo

Part B Multiple Ascending Dose (MAD) - RV299/Placebo

EXPERIMENTAL

Participants will receive RV299 or placebo twice daily on Day 1-4 and a single dose on Day 5. Participants in each cohort will receive ascending doses of RV299, depending on emerging safety and PK data. Part B, Cohort 3 will investigate interaction between midazolam and RV299. Participants will receive a single dose of midazolam on Day 1 and Day 7, and receive RV299 twice daily on Days 2 - 6

Drug: RV299; Drug: Placebo; Drug: Midazolam

Part C Food Effect (FE)- RV299

EXPERIMENTAL

Participants will receive RV299 as a single dose on Day 1 and Day 5; treatment will be administered in the first treatment period fasted and the second treatment period fed (or vice versa).

Drug: RV299

Interventions

RV299 DRUG

Oral Suspension

Part A Single Ascending Dose (SAD) - RV299/Placebo; Part B Multiple Ascending Dose (MAD) - RV299/Placebo; Part C Food Effect (FE)- RV299

Placebo DRUG

matching placebo

Part A Single Ascending Dose (SAD) - RV299/Placebo; Part B Multiple Ascending Dose (MAD) - RV299/Placebo

Midazolam DRUG

pre-filled oral syringe

Part B Multiple Ascending Dose (MAD) - RV299/Placebo

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• An understanding, ability, and willingness to fully comply with trial procedures and restrictions.

You may not qualify if:

• 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;
• Has a haemoglobin, platelet count, total white blood cell count, lymphocyte or monocyte count less than lower limit of normal (LLN) (up to two repeats may be taken).
• Has total bilirubin, ALT or AST consistently greater than ULN at Screening (up to two repeats may be taken).
• Any other abnormal findings on vital signs, ECG, physical examination or laboratory evaluation of blood and urine samples that the Investigator judges as likely to interfere with the trial or pose an additional risk in participating.
• Positive test results for alcohol or drugs of abuse at screening or Day-1/Day-2.
• History or clinical evidence of substance and/or alcohol abuse within the 2 years before screening.
• Treatment with an investigational drug within 90 days or 5 half-lives preceding the first dose of trial medication (or as determined by the local requirement, whichever is longer).
• Use of tobacco in any form (e.g., smoking or chewing) or other nicotine containing products in any form (e.g., gum, patch, electronic cigarettes) within 3 months prior to the planned first day of dosing.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Richmond Pharmacology Ltd

London, Greater London, SE1 1YR, United Kingdom

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections; Bronchiolitis

Interventions

Midazolam

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections; Bronchitis; Respiratory Tract Infections; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part A and B (Cohorts 1 -2) participants and care providers will remain blinded to study allocation. Part B (Cohort 3) and Part C participants will not be blinded to their study treatment. The placebo bottle will be covered with a paper sleeve to ensure contents remain blinded. Pharmacy staff preparing investigational products will not be blinded to drug assignment. During the trial, individual randomisation codes will be kept in the site's clinical trials pharmacy, accessible to the pharmacy personnel only. Drug accountability will be reviewed by an unblinded CRA. Sponsor staff involved in clinical decision-making (e.g. Safety Review Committee) will be blinded to drug assignment. Sponsor staff performing PK analysis will be unblinded but will deliver blinded PK data and reports to the blinded sponsor and Investigator teams. A cardiologist will examine all ECG recordings of Part B participants with readers blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2022
• First Posted: September 13, 2023
• Study Start: November 12, 2021
• Primary Completion: July 27, 2022
• Study Completion: July 27, 2022
• Last Updated: September 13, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)