Respiratory Syncytial Virus InfectionsPhase 1NCT06033612
Safety, Tolerability, Pharmacokinetics, and Food Effect Study of RV299 in Healthy Adults
A Phase 1 study testing RV299 and Midazolam in people with Respiratory Syncytial Virus Infections, run by Pfizer at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Respiratory Syncytial Virus Infections
- What is being tested?
- RV299 and Midazolam
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 12 Nov 2021to 27 Jul 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.)
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- 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.
- Has used any other prescription medication within 14 days or 10 half-lives (whichever is longer) prior to Day 1 of the dosing period that the Investigator judges is likely to interfere with the trial or pose an additional risk in participating.
- Has used any over-the-counter medication (including multivitamin, herbal, or homeopathic preparations; excluding paracetamol - up to 2g paracetamol per day permitted) during the 7 days or 10 half-lives of the drug (whichever is longer) prior to Day 1 of the dosing period, that the Investigator judges is likely to interfere with the trial or pose an additional risk in participating.
- Consumption of herbal remedies or dietary supplements containing St. John's Wort in the three weeks before the planned Day 1 of the dosing period.
- Known or suspected intolerance or hypersensitivity to the investigational product, any closely related compound, or any of the stated ingredients.
- History of significant allergic reaction (anaphylaxis, angioedema) to any product (food, pharmaceutical, etc).
- Donation of blood or blood products (excluding plasma) within 90 days prior to trial medication administration.
- Has a mental incapacity or language barriers precluding adequate understanding, co-operation, and compliance with the trial requirements.
- An inability to follow a standardised diet and meal schedule or inability to fast, as required during the trial.
- Participants with veins on either arm that are unsuitable for intravenous puncture or cannulation.
- Prior screen failure (where the cause of the screen failure is not deemed to be temporary), randomisation, participation, or enrolment in this trial. Participants who initially failed due to temporary non-medically significant issues are eligible for re-screening once the cause has resolved.
- Participants who have received or are planning on receiving a COVID-19 vaccination two weeks before first dose administration, or within one week after the final follow-up visit for the study.
- Known or suspected intolerance or hypersensitivity to the investigational product, the non-investigational product (midazolam), any closely related compound, or any of the stated ingredients.
- Female participants currently on combined hormonal contraception or hormonal replacement therapy containing oestradiol or ethinyloestradiol.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Richmond Pharmacology Ltd
London, Greater London, SE1 1YR
About this study
Official title: A Randomised, Double Blinded, Placebo-controlled Single and Multiple Ascending Dose Study of Orally Administered RV299 to Evaluate Safety, Tolerability, Pharmacokinetics and Food Effect in Healthy Adult Participants
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.
Read the detailed description
This is a randomised, double blind, placebo-controlled Phase I study to assess the safety, tolerability, pharmacokinetics and food effect of RV299 in healthy participants aged ≥ 20 to ≤ 40 years.
The clinical study consists of 3 parts (Parts A - C):
Part A: single ascending doses (SAD) of RV299 in healthy adult Caucasian participants (up to 3 dose levels of RV299 in 3 cohorts; 6 participants/cohort)
Part B: multiple ascending doses (MAD) of RV299 in healthy adult Caucasian participants (up to 2 dose levels of RV299 in 2 cohorts of 8 participants dosed for 5 consecutive days). Part B will incorporate a drug-drug interaction (DDI) design to investigate interaction between RV299 and midazolam in one cohort (Cohort 3) of 8 participants.
Part C: food effect (FE) in healthy adult Caucasian participants (one cohort of 8 participants to be randomised to receive either RV299 in the first treatment period fasted and in the second treatment period fed, or vice versa)
The study will be conducted as an adaptive integrated design since various study parts can be triggered at appropriate times during the conduct of other parts of the study. Dose escalation to the following scheduled dose or progression to a consecutive part of the study will only occur after satisfactory review of all safety, tolerability and pharmacokinetic (PK) data.
- Conditions
- Respiratory Syncytial Virus Infections
- Being tested
- RV299, Placebo, Midazolam
- Keywords
- RSV, bronchiolitis, lower respiratory tract infection, LRTI
- Medical subject headings
- Respiratory Syncytial Virus Infections, Bronchiolitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RV299Drug
Oral Suspension
PlaceboDrug
matching placebo
MidazolamDrug
pre-filled oral syringe
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: 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). Receives: Drug: RV299 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: 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.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: 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.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: 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.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: 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.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: 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) from time zero to 24 hours post-dose (AUC0-24h) following single and multiple doses of RV299.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: Parts A, B and C: pre-dose (Day 1) to 24 hours after final dose of RV299
Assess area under the plasma concentration-time curve of RV299 from time zero to infinity (AUC0-inf) following single and multiple doses of RV299.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: Parts A, B and C: pre-dose (Day 1) to 7 days after final dose of RV299
Assess accumulation ratio of RV299 based on AUC0-tau following multiple doses of RV299.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: Part B only: pre-dose (Day 1) to 7 days after final dose of RV299 (at Day 5)
Assess minimum blood plasma concentration (Cmin) of RV299 between administration of two doses of RV299.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: Parts B and C: pre-dose (Day 1) to 7 days after final dose of RV299
Assess plasma clearance (rate of removal of RV299 from plasma) (CL/F) following single and multiple doses of RV299.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: Parts A, B and C: pre-dose (Day 1) to 7 days after final dose of RV299
Assess apparent volume of distribution (VZ/F) of RV299 following single and multiple doses of RV299.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: 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 after dosing in the fed and fasted states.
First dose of RV299 will be given while participant is in the fasted state; second dose will be given after patient has eaten (and vice-versa). Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Measured: Part C only: pre-dose (Day 1) to 7 days after second (final) dose (Day 5).
Assess maximum plasma concentration (Cmax) of RV299 after dosing in the fed and fasted states.
First dose of RV299 will be given while participant is in the fasted state; second dose will be given after patient has eaten (and vice-versa). Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Measured: Part C only: pre-dose (Day 1) to 7 days after second (final) dose (at Day 5).
Characterise steady-state plasma pharmacokinetics (PK) of RV299 following multiple doses of RV299 by comparing AUC against dosing intervals.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: Part B only: pre-dose (Day 1) to 7 days after final dose of RV299 (at Day 5).
Assess area under the plasma concentration versus time curve from time zero to 12 hours post-dose (AUC0-12) following multiple doses of RV299.
Pharmacokinetic analysis will include listings and summaries of RV299 concentration by time point, derived PK, parameters and analysis of relationship with dose and body weight
Measured: Part B only: pre-dose to 12 hours following administration of first dose of RV299 (Day 1) and final dose (Day 5)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2023
- Study start12 Nov 2021
- Primary completion27 Jul 2022
- Study completion27 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory Syncytial Virus InfectionsStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06033612
- Sponsor's protocol ID
- REVD001
- Other IDs
- C5251001
- Status last verified
- Sep 2023
- First submitted
- 11 Aug 2022
- Last updated
- 13 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double Blinded, Placebo-controlled Single and Multiple Ascending Dose Study of Orally Administered RV299 to Evaluate Safety, Tolerability, Pharmacokinetics and Food Effect in Healthy Adult Participants
- ClinicalTrials.gov ID
- NCT06033612
- Acronym / sponsor ID
- REVD001
- Conditions
- Respiratory Syncytial Virus Infections
- Keywords
- RSV, bronchiolitis, lower respiratory tract infection, LRTI
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 12 Nov 2021 (actual)
- Primary completion
- 27 Jul 2022 (actual)
- Study completion
- 27 Jul 2022 (actual)
- First posted
- 13 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a randomised, double blind, placebo-controlled Phase I study to assess the safety, tolerability, pharmacokinetics and food effect of RV299 in healthy participants aged ≥ 20 to ≤ 40 years.
The clinical study consists of 3 parts (Parts A - C):
Part A: single ascending doses (SAD) of RV299 in healthy adult Caucasian participants (up to 3 dose levels of RV299 in 3 cohorts; 6 participants/cohort)
Part B: multiple ascending doses (MAD) of RV299 in healthy adult Caucasian participants (up to 2 dose levels of RV299 in 2 cohorts of 8 participants dosed for 5 consecutive days). Part B will incorporate a drug-drug interaction (DDI) design to investigate interaction between RV299 and midazolam in one cohort (Cohort 3) of 8 participants.
Part C: food effect (FE) in healthy adult Caucasian participants (one cohort of 8 participants to be randomised to receive either RV299 in the first treatment period fasted and in the second treatment period fed, or vice versa)
The study will be conducted as an adaptive integrated design since various study parts can be triggered at appropriate times during the conduct of other parts of the study. Dose escalation to the following scheduled dose or progression to a consecutive part of the study will only occur after satisfactory review of all safety, tolerability and pharmacokinetic (PK) data.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A Single Ascending Dose (SAD) - RV299/Placebo | Experimental | Drug: RV299, Drug: PlaceboParticipants 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. |
| Part B Multiple Ascending Dose (MAD) - RV299/Placebo | Experimental | Drug: RV299, Drug: Placebo, Drug: MidazolamParticipants 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 |
| Part C Food Effect (FE)- RV299 | Experimental | Drug: RV299Participants 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). |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (28 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RV299Oral Suspension | Drug | Part A Single Ascending Dose (SAD) - RV299/Placebo, Part B Multiple Ascending Dose (MAD) - RV299/Placebo, Part C Food Effect (FE)- RV299 |
| Placebomatching placebo | Drug | Part A Single Ascending Dose (SAD) - RV299/Placebo, Part B Multiple Ascending Dose (MAD) - RV299/Placebo |
| Midazolampre-filled oral syringe | Drug | Part B Multiple Ascending Dose (MAD) - RV299/Placebo |
Primary outcome
Number of participants with treatment-emergent adverse events (TEAE) as assessed by CTCAE V5.0.
Time frame: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
Listings and summary tables of AEs will be based on TEAEs (defined as events starting, or worsening, after the first dose of RV299).
Evaluate the proportion of participants with clinically significant shifts in haematology/clinical chemistry/coagulation/urinalysis values from baseline following dosing with RV299
Time frame: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
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.
Evaluate the proportion of subjects with changes in ECG measurements from baseline following dosing with RV299
Time frame: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
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.
Evaluate safety and tolerability of RV299 by assessing changes from baseline in tympanic temperature (vital sign parameters)
Time frame: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
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.
Evaluate safety and tolerability of RV299 by assessing changes from baseline in blood pressure (BP) (vital sign parameters).
Time frame: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
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.
Evaluate safety and tolerability of RV299 by assessing changes from baseline in heart rate (HR) (vital sign parameters).
Time frame: PPart A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
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.
Evaluate safety and tolerability of RV299 by assessing changes from baseline in respiratory rate (vital sign parameters).
Time frame: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose
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.
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.
Time frame: 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.
Pharmacokinetic analysis will include listings and summaries of midazolam concentration by time point and analysis of relationship with dose and body weight.
Assess time to maximum plasma concentration (tmax) of midazolam (as index substrate) before and after dosing with RV299.
Time frame: 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.
Pharmacokinetic analysis will include listings and summaries of midazolam concentration by time point and analysis of relationship with dose and body weight
Assess terminal half life of (t1/2) of midazolam (as index substrate) before and after dosing with RV299.
Time frame: 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.
Pharmacokinetic analysis will include listings and summaries of midazolam concentration by time point and analysis of relationship with dose and body weight
Assess maximum plasma concentration (Cmax) of midazolam (as index substrate) before and after dosing with RV299.
Time frame: 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.
Pharmacokinetic analysis will include listings and summaries of midazolam concentration by time point and analysis of relationship with dose and body weight
15 secondary outcomes
Characterise plasma pharmacokinetics (PK) of RV299 by assessing time to maximum plasma concentration (tmax) following single and multiple doses of RV299.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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) from time zero to 24 hours post-dose (AUC0-24h) following single and multiple doses of RV299.
Time frame: Parts A, B and C: pre-dose (Day 1) to 24 hours after final dose of RV299
Assess area under the plasma concentration-time curve of RV299 from time zero to infinity (AUC0-inf) following single and multiple doses of RV299.
Time frame: Parts A, B and C: pre-dose (Day 1) to 7 days after final dose of RV299
Assess accumulation ratio of RV299 based on AUC0-tau following multiple doses of RV299.
Time frame: Part B only: pre-dose (Day 1) to 7 days after final dose of RV299 (at Day 5)
Assess minimum blood plasma concentration (Cmin) of RV299 between administration of two doses of RV299.
Time frame: Parts B and C: pre-dose (Day 1) to 7 days after final dose of RV299
Assess plasma clearance (rate of removal of RV299 from plasma) (CL/F) following single and multiple doses of RV299.
Time frame: Parts A, B and C: pre-dose (Day 1) to 7 days after final dose of RV299
Assess apparent volume of distribution (VZ/F) of RV299 following single and multiple doses of RV299.
Time frame: 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 after dosing in the fed and fasted states.
Time frame: Part C only: pre-dose (Day 1) to 7 days after second (final) dose (Day 5).
Assess maximum plasma concentration (Cmax) of RV299 after dosing in the fed and fasted states.
Time frame: Part C only: pre-dose (Day 1) to 7 days after second (final) dose (at Day 5).
Characterise steady-state plasma pharmacokinetics (PK) of RV299 following multiple doses of RV299 by comparing AUC against dosing intervals.
Time frame: Part B only: pre-dose (Day 1) to 7 days after final dose of RV299 (at Day 5).
Assess area under the plasma concentration versus time curve from time zero to 12 hours post-dose (AUC0-12) following multiple doses of RV299.
Time frame: Part B only: pre-dose to 12 hours following administration of first dose of RV299 (Day 1) and final dose (Day 5)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2023.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RV299 and Midazolam in people with Respiratory Syncytial Virus Infections, run by Pfizer at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-emergent adverse events (TEAE) as assessed by CTCAE V5.0. (time frame: Part A: 7 days after single dose; Part B: 28 days after final dose; Part C: 7 days after final dose). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.