Back to resultsDrug Interaction Study With RV521 in Healthy Volunteer Subjects
Primary Purpose
Respiratory Syncytial Virus Infections
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Itraconazole
Verapamil
Rifampicin
Midazolam
Placebo for RV521
RV521
Sponsored by
About this trial
This is an interventional treatment trial for Respiratory Syncytial Virus Infections
Eligibility Criteria
Inclusion Criteria:
- Age 18 to 45 years, inclusive
- Willing to comply with protocol defined contraception requirements
- In good health with no history of major medical conditions
- A body mass index (BMI) of 18 - 25 kg/m2
Exclusion Criteria:
- Evidence of any clinically significant or currently active major medical condition
- Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab)
- Not willing to comply with protocol defined restrictions for intake of drugs of abuse, alcohol, nicotine-containing products, medication (prescription, OTC, herbal, vitamins/minerals etc) and specified food and drink products
Sites / Locations
- Richmond Pharmacology Ltd
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
RV521 plus Itraconazole
RV521 plus Verapamil
RV521 plus Rifampicin
RV521 plus Midazolam
Placebo plus Midazolam
Arm Description
RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D7 plus Itraconazole 100 mg capsules for oral administration, a 200 mg dose administered once daily on D4 - D10, inclusive
RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D11 plus Verapamil, 80 mg tablets for oral administration, an 80 mg dose administered TDS daily on D4 - D14, inclusive
RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D10 plus Rifadin, Rifampicin, 300 mg capsules for oral administration, a 600 mg dose administered once daily on D4 - D10, inclusive
RV521 drug substance in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15
Placebo for RV521 in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15
Outcomes
Primary Outcome Measures
Effect of RV521 on Cmax of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of RV521 on tmax of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of RV521 on t1/2 of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of RV521 on AUC of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of RV521 on CL/F of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on Cmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on tmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on t1/2 of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on AUC of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on CL/F of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on Cmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on tmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on t1/2 of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on AUC of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on CL/F of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on Cmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on tmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on t1/2 of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on AUC of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on CL/F of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Secondary Outcome Measures
Number of subjects with treatment-related adverse events as assessed by NCI CTCAE V5.0
The number of subjects with treatment-related adverse events will be summarised by treatment group using descriptive statistics
Number of subjects with QT/QTc interval changes relative to baseline who received RV521 (monotherapy), Midazolam (monotherapy) or RV521 and Midazolam (combination therapy)
Descriptive statistics will be given by time point and dose-group for absolute values and change from baseline. Results will be tabulated and for QTc, the difference to time matched placebo will also be displayed
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03782662
Brief Title
Drug Interaction Study With RV521 in Healthy Volunteer Subjects
Official Title
An Adaptive, Part Open-label, Part Randomised Phase 1 Clinical Trial in Healthy Volunteers to Study Drug Interactions With RV521 Including Those Mediated by CYP3A4 and P-glycoprotein
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
November 6, 2018 (Actual)
Primary Completion Date
March 17, 2019 (Actual)
Study Completion Date
March 17, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main aim of this study is to determine whether RV521 interacts with any other medication using four licensed medicines (midazolam, itraconazole, rifampicin and verapamil) that are known to have specific effects on enzymes and transporter proteins that influence the absorption of drugs
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Syncytial Virus Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
82 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RV521 plus Itraconazole
Arm Type
Experimental
Arm Description
RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D7 plus Itraconazole 100 mg capsules for oral administration, a 200 mg dose administered once daily on D4 - D10, inclusive
Arm Title
RV521 plus Verapamil
Arm Type
Experimental
Arm Description
RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D11 plus Verapamil, 80 mg tablets for oral administration, an 80 mg dose administered TDS daily on D4 - D14, inclusive
Arm Title
RV521 plus Rifampicin
Arm Type
Experimental
Arm Description
RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D10 plus Rifadin, Rifampicin, 300 mg capsules for oral administration, a 600 mg dose administered once daily on D4 - D10, inclusive
Arm Title
RV521 plus Midazolam
Arm Type
Experimental
Arm Description
RV521 drug substance in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15
Arm Title
Placebo plus Midazolam
Arm Type
Placebo Comparator
Arm Description
Placebo for RV521 in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15
Intervention Type
Drug
Intervention Name(s)
Itraconazole
Intervention Description
Itraconazole capsules
Intervention Type
Drug
Intervention Name(s)
Verapamil
Intervention Description
Verapamil tablets
Intervention Type
Drug
Intervention Name(s)
Rifampicin
Other Intervention Name(s)
Rifadin
Intervention Description
Rifampicin capsules
Intervention Type
Drug
Intervention Name(s)
Midazolam
Other Intervention Name(s)
Midazolam Prefilled Syringe, Buccolam
Intervention Description
Midazolam oromucosal solution
Intervention Type
Drug
Intervention Name(s)
Placebo for RV521
Intervention Description
Placebo for RV521 capsules
Intervention Type
Drug
Intervention Name(s)
RV521
Intervention Description
RV521 capsules
Primary Outcome Measure Information:
Title
Effect of RV521 on Cmax of Midazolam
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 17
Title
Effect of RV521 on tmax of Midazolam
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 17
Title
Effect of RV521 on t1/2 of Midazolam
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 17
Title
Effect of RV521 on AUC of Midazolam
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 17
Title
Effect of RV521 on CL/F of Midazolam
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 17
Title
Effect of itraconazole on Cmax of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 12
Title
Effect of itraconazole on tmax of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 12
Title
Effect of itraconazole on t1/2 of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 12
Title
Effect of itraconazole on AUC of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 12
Title
Effect of itraconazole on CL/F of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 12
Title
Effect of verapamil on Cmax of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 16
Title
Effect of verapamil on tmax of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 16
Title
Effect of verapamil on t1/2 of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 16
Title
Effect of verapamil on AUC of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 16
Title
Effect of verapamil on CL/F of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 16
Title
Effect of rifampicin on Cmax of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 15
Title
Effect of rifampicin on tmax of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 15
Title
Effect of rifampicin on t1/2 of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 15
Title
Effect of rifampicin on AUC of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 15
Title
Effect of rifampicin on CL/F of RV521
Description
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time Frame
Baseline to study day 15
Secondary Outcome Measure Information:
Title
Number of subjects with treatment-related adverse events as assessed by NCI CTCAE V5.0
Description
The number of subjects with treatment-related adverse events will be summarised by treatment group using descriptive statistics
Time Frame
Screening to final study visit (performed at 7 days following the last dose of any intervention)
Title
Number of subjects with QT/QTc interval changes relative to baseline who received RV521 (monotherapy), Midazolam (monotherapy) or RV521 and Midazolam (combination therapy)
Description
Descriptive statistics will be given by time point and dose-group for absolute values and change from baseline. Results will be tabulated and for QTc, the difference to time matched placebo will also be displayed
Time Frame
Baseline to to final study visit (performed at 7 days following the last dose of any intervention)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age 18 to 45 years, inclusive
Willing to comply with protocol defined contraception requirements
In good health with no history of major medical conditions
A body mass index (BMI) of 18 - 25 kg/m2
Exclusion Criteria:
Evidence of any clinically significant or currently active major medical condition
Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab)
Not willing to comply with protocol defined restrictions for intake of drugs of abuse, alcohol, nicotine-containing products, medication (prescription, OTC, herbal, vitamins/minerals etc) and specified food and drink products
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lorch, MD
Organizational Affiliation
Richmond Pharmacology Limited
Official's Role
Principal Investigator
Facility Information:
Facility Name
Richmond Pharmacology Ltd
City
London
ZIP/Postal Code
SE1 1YR
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Drug Interaction Study With RV521 in Healthy Volunteer Subjects
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