Pharmacokinetics of Plasma Doravirine Once Daily Over 72 Hours Following Drug Intake Cessation in Healthy Volunteers
Primary Purpose
Human Immunodeficiency Virus
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Doravirine
Sponsored by
About this trial
This is an interventional other trial for Human Immunodeficiency Virus
Eligibility Criteria
Inclusion Criteria:
- The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
- Male or non-pregnant, non-lactating females.
- Between 18 to 65 years, inclusive
- Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive
- ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat is allowed for eligibility determination.
- Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 4 weeks after the study. Any contraception method must be used consistently, in accordance with the approved product label and for at least 4 weeks after discontinuation of IMP.
- Men who have partners who are women of childbearing potential must be using an adequate method of contraception to avoid pregnancy in their partner throughout the study and for a period of at least 4 weeks after the study. Any contraception method must be used consistently, in accordance with the approved product label and for at least four weeks after discontinuation of IMP.
- Willing to consent to their personal details being entered onto the TOPS database
- Willing to provide proof of identity by photographic ID at screen and any subsequent visit
- Registered with a GP in the UK
Exclusion Criteria:
- Any clinically significant acute or chronic medical illness
- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
- Positive blood screen for hepatitis B surface antigen or C antibody
- Positive blood screen for HIV-1 or 2 by antibody/antigen assay
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- History or presence of allergy to the study drugs and their components
- Current or recent (within three months) gastrointestinal disease
- Known intolerance of lactose monohydrate, sunset yellow aluminium lake (E110), and patients with galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
- Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study
- Exposure to any investigational drug (or placebo) or participation in a clinical study involving the donation of blood samples within three months of first dose of study drug
- Use of any other drugs (unless approved by the Investigator), including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs.
- Females of childbearing potential without the use of effective non-hormonal birth control methods, or not willing to continue practising these birth control methods for at least four weeks after the end of the treatment period
Sites / Locations
- Chelsea and Westminster Hospital NHS Foundation Trust
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Study intervention
Arm Description
Pifeltro® (doravirine 100mg) daily dose for 7 days
Outcomes
Primary Outcome Measures
Steady state plasma concentrations of doravirine after drug intake cessation up to 72 hours post-dose.
Following cessation of daily doravirine, plasma concentrations of drug to be taken before last dose and at 11 further timepoints over 72 hours.
Secondary Outcome Measures
Incidence of treatment-emergent adverse events
All adverse events to be recorded and reported during the study up to last visit.
Full Information
NCT ID
NCT03894124
First Posted
March 26, 2019
Last Updated
August 9, 2019
Sponsor
Chelsea and Westminster NHS Foundation Trust
Collaborators
Merck Sharp & Dohme LLC, Imperial College London, University of Liverpool
1. Study Identification
Unique Protocol Identification Number
NCT03894124
Brief Title
Pharmacokinetics of Plasma Doravirine Once Daily Over 72 Hours Following Drug Intake Cessation in Healthy Volunteers
Official Title
Pharmacokinetics of Plasma Doravirine Once Daily Over 72 Hours Following Drug Intake Cessation in Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
June 12, 2019 (Actual)
Primary Completion Date
July 25, 2019 (Actual)
Study Completion Date
August 6, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chelsea and Westminster NHS Foundation Trust
Collaborators
Merck Sharp & Dohme LLC, Imperial College London, University of Liverpool
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
Study to assess the pharmacokinetics of plasma doravirine once daily over 72 hours following drug intake cessation at steady-state in healthy volunteers
Detailed Description
The administration of combination antiretroviral therapy (cART) to HIV-infected patients has been associated with a dramatic reduction in AIDS-related morbidity and mortality. The key to successful HIV drug treatment is adhering to the prescribed combination every day. The approval of single tablet combinations (STRs) provides HIV care providers with a "one tablet once a day" therapy, making adherence much easier for patients. However, in HIV therapy, successful adherence also means attention to intervals between doses or dietary restrictions. Ideally, to guarantee long-term virological response, HIV-infected patients should take their cART every day at the same time. However, cART is for life and doses can be forgotten or delayed. For this study 14 healthy volunteers will receive Pifeltro® (doravirine 100mg tablets) daily for 7 days to reach steady state. Following the last dose samples will be taken for pharmacokinetic testing over 72 hours.
The incidence of adverse events between enrolment to the study (day 1) and last visit (day 20-23) will be recorded.
Blood, urine and faecal samples from study subjects will be taken for use in planned exploratory research and for use in future research:
Analyses looking at genes which affect drug disposition (pharmacogenomics); the impact of doravirine intake on platelet function and markers of platelet and endothelial cell activation; metabolic changes associated with doravirine.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Single cohort pharmacokinetic (PK) study
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Study intervention
Arm Type
Other
Arm Description
Pifeltro® (doravirine 100mg) daily dose for 7 days
Intervention Type
Drug
Intervention Name(s)
Doravirine
Other Intervention Name(s)
Pifeltro
Intervention Description
Non-nucleoside reverse transcriptase inhibitor. Administered as film coated tablet.
Primary Outcome Measure Information:
Title
Steady state plasma concentrations of doravirine after drug intake cessation up to 72 hours post-dose.
Description
Following cessation of daily doravirine, plasma concentrations of drug to be taken before last dose and at 11 further timepoints over 72 hours.
Time Frame
72 hours from treatment cessation; days 7-10 inclusive from enrolment
Secondary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events
Description
All adverse events to be recorded and reported during the study up to last visit.
Time Frame
From enrolment to last visit; last visit will be between days 20-23 from enrolment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
Male or non-pregnant, non-lactating females.
Between 18 to 65 years, inclusive
Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive
ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat is allowed for eligibility determination.
Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 4 weeks after the study. Any contraception method must be used consistently, in accordance with the approved product label and for at least 4 weeks after discontinuation of IMP.
Men who have partners who are women of childbearing potential must be using an adequate method of contraception to avoid pregnancy in their partner throughout the study and for a period of at least 4 weeks after the study. Any contraception method must be used consistently, in accordance with the approved product label and for at least four weeks after discontinuation of IMP.
Willing to consent to their personal details being entered onto the TOPS database
Willing to provide proof of identity by photographic ID at screen and any subsequent visit
Registered with a GP in the UK
Exclusion Criteria:
Any clinically significant acute or chronic medical illness
Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
Positive blood screen for hepatitis B surface antigen or C antibody
Positive blood screen for HIV-1 or 2 by antibody/antigen assay
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
History or presence of allergy to the study drugs and their components
Current or recent (within three months) gastrointestinal disease
Known intolerance of lactose monohydrate, sunset yellow aluminium lake (E110), and patients with galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study
Exposure to any investigational drug (or placebo) or participation in a clinical study involving the donation of blood samples within three months of first dose of study drug
Use of any other drugs (unless approved by the Investigator), including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs.
Females of childbearing potential without the use of effective non-hormonal birth control methods, or not willing to continue practising these birth control methods for at least four weeks after the end of the treatment period
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marta Boffito
Organizational Affiliation
Chelsea and Westminster NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chelsea and Westminster Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
SW10 9NH
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30272231
Citation
Elliot ER, Cerrone M, Challenger E, Else L, Amara A, Bisdomini E, Khoo S, Owen A, Boffito M. Pharmacokinetics of dolutegravir with and without darunavir/cobicistat in healthy volunteers. J Antimicrob Chemother. 2019 Jan 1;74(1):149-156. doi: 10.1093/jac/dky384. Erratum In: J Antimicrob Chemother. 2019 May 1;74(5):1466. Challenger, Elizabeth [added].
Results Reference
background
PubMed Identifier
30047107
Citation
Wilby KJ, Eissa NA. Clinical Pharmacokinetics and Drug Interactions of Doravirine. Eur J Drug Metab Pharmacokinet. 2018 Dec;43(6):637-644. doi: 10.1007/s13318-018-0497-3.
Results Reference
background
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Pharmacokinetics of Plasma Doravirine Once Daily Over 72 Hours Following Drug Intake Cessation in Healthy Volunteers
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