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Drug Interaction Study With RV521 in Healthy Volunteer Subjects

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ClinicalTrials.gov Identifier: NCT03782662
Recruitment Status : Completed
First Posted : December 20, 2018
Last Update Posted : May 23, 2019
Sponsor:
Information provided by (Responsible Party):
ReViral Ltd

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

Condition or disease Intervention/treatment Phase
Respiratory Syncytial Virus Infections Drug: Itraconazole Drug: Verapamil Drug: Rifampicin Drug: Midazolam Drug: Placebo for RV521 Drug: RV521 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : November 6, 2018
Actual Primary Completion Date : March 17, 2019
Actual Study Completion Date : March 17, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: RV521 plus Itraconazole
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
Drug: Itraconazole
Itraconazole capsules

Drug: RV521
RV521 capsules

Experimental: RV521 plus Verapamil
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
Drug: Verapamil
Verapamil tablets

Drug: RV521
RV521 capsules

Experimental: RV521 plus Rifampicin
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
Drug: Rifampicin
Rifampicin capsules
Other Name: Rifadin

Drug: RV521
RV521 capsules

Experimental: RV521 plus Midazolam
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
Drug: Midazolam
Midazolam oromucosal solution
Other Names:
  • Midazolam Prefilled Syringe
  • Buccolam

Drug: RV521
RV521 capsules

Placebo Comparator: Placebo plus Midazolam
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
Drug: Midazolam
Midazolam oromucosal solution
Other Names:
  • Midazolam Prefilled Syringe
  • Buccolam

Drug: Placebo for RV521
Placebo for RV521 capsules




Primary Outcome Measures :
  1. Effect of RV521 on Cmax of Midazolam [ Time Frame: Baseline to study day 17 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  2. Effect of RV521 on tmax of Midazolam [ Time Frame: Baseline to study day 17 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  3. Effect of RV521 on t1/2 of Midazolam [ Time Frame: Baseline to study day 17 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  4. Effect of RV521 on AUC of Midazolam [ Time Frame: Baseline to study day 17 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  5. Effect of RV521 on CL/F of Midazolam [ Time Frame: Baseline to study day 17 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  6. Effect of itraconazole on Cmax of RV521 [ Time Frame: Baseline to study day 12 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  7. Effect of itraconazole on tmax of RV521 [ Time Frame: Baseline to study day 12 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  8. Effect of itraconazole on t1/2 of RV521 [ Time Frame: Baseline to study day 12 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  9. Effect of itraconazole on AUC of RV521 [ Time Frame: Baseline to study day 12 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  10. Effect of itraconazole on CL/F of RV521 [ Time Frame: Baseline to study day 12 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  11. Effect of verapamil on Cmax of RV521 [ Time Frame: Baseline to study day 16 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  12. Effect of verapamil on tmax of RV521 [ Time Frame: Baseline to study day 16 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  13. Effect of verapamil on t1/2 of RV521 [ Time Frame: Baseline to study day 16 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  14. Effect of verapamil on AUC of RV521 [ Time Frame: Baseline to study day 16 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  15. Effect of verapamil on CL/F of RV521 [ Time Frame: Baseline to study day 16 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  16. Effect of rifampicin on Cmax of RV521 [ Time Frame: Baseline to study day 15 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  17. Effect of rifampicin on tmax of RV521 [ Time Frame: Baseline to study day 15 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  18. Effect of rifampicin on t1/2 of RV521 [ Time Frame: Baseline to study day 15 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  19. Effect of rifampicin on AUC of RV521 [ Time Frame: Baseline to study day 15 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics

  20. Effect of rifampicin on CL/F of RV521 [ Time Frame: Baseline to study day 15 ]
    The specified pharmacokinetic parameter will be summarised using descriptive statistics


Secondary Outcome Measures :
  1. Number of subjects with treatment-related adverse events as assessed by NCI CTCAE V5.0 [ Time Frame: Screening to final study visit (performed at 7 days following the last dose of any intervention) ]
    The number of subjects with treatment-related adverse events will be summarised by treatment group using descriptive statistics

  2. Number of subjects with QT/QTc interval changes relative to baseline who received RV521 (monotherapy), Midazolam (monotherapy) or RV521 and Midazolam (combination therapy) [ Time Frame: Baseline to to final study visit (performed at 7 days following the last dose of any intervention) ]
    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



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03782662


Locations
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United Kingdom
Richmond Pharmacology Ltd
London, United Kingdom, SE1 1YR
Sponsors and Collaborators
ReViral Ltd
Investigators
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Principal Investigator: Lorch, MD Richmond Pharmacology Limited

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Responsible Party: ReViral Ltd
ClinicalTrials.gov Identifier: NCT03782662     History of Changes
Other Study ID Numbers: REVC004
2018-003256-21 ( EudraCT Number )
First Posted: December 20, 2018    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Syncytial Virus Infections
Virus Diseases
Pneumovirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Itraconazole
Hydroxyitraconazole
Rifampin
Verapamil
Midazolam
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors