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Pharmacokinetics of Plasma Doravirine Once Daily Over 72 Hours Following Drug Intake Cessation in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT03894124
Recruitment Status : Completed
First Posted : March 28, 2019
Last Update Posted : August 12, 2019
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Imperial College London
University of Liverpool
Information provided by (Responsible Party):
Chelsea and Westminster NHS Foundation Trust

Tracking Information
First Submitted Date  ICMJE March 26, 2019
First Posted Date  ICMJE March 28, 2019
Last Update Posted Date August 12, 2019
Actual Study Start Date  ICMJE June 12, 2019
Actual Primary Completion Date July 25, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2019)
Steady state plasma concentrations of doravirine after drug intake cessation up to 72 hours post-dose. [ Time Frame: 72 hours from treatment cessation; days 7-10 inclusive from enrolment ]
Following cessation of daily doravirine, plasma concentrations of drug to be taken before last dose and at 11 further timepoints over 72 hours.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2019)
Incidence of treatment-emergent adverse events [ Time Frame: From enrolment to last visit; last visit will be between days 20-23 from enrolment ]
All adverse events to be recorded and reported during the study up to last visit.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics of Plasma Doravirine Once Daily Over 72 Hours Following Drug Intake Cessation in Healthy Volunteers
Official Title  ICMJE Pharmacokinetics of Plasma Doravirine Once Daily Over 72 Hours Following Drug Intake Cessation in Healthy Volunteers
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Single cohort pharmacokinetic (PK) study
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Human Immunodeficiency Virus
Intervention  ICMJE Drug: Doravirine
Non-nucleoside reverse transcriptase inhibitor. Administered as film coated tablet.
Other Name: Pifeltro
Study Arms  ICMJE Study intervention
Pifeltro® (doravirine 100mg) daily dose for 7 days
Intervention: Drug: Doravirine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 27, 2019)
14
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 6, 2019
Actual Primary Completion Date July 25, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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
  2. Male or non-pregnant, non-lactating females.
  3. Between 18 to 65 years, inclusive
  4. Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive
  5. 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.
  6. 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.
  7. 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.
  8. Willing to consent to their personal details being entered onto the TOPS database
  9. Willing to provide proof of identity by photographic ID at screen and any subsequent visit
  10. Registered with a GP in the UK

Exclusion Criteria:

  1. Any clinically significant acute or chronic medical illness
  2. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
  3. Positive blood screen for hepatitis B surface antigen or C antibody
  4. Positive blood screen for HIV-1 or 2 by antibody/antigen assay
  5. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  6. History or presence of allergy to the study drugs and their components
  7. Current or recent (within three months) gastrointestinal disease
  8. Known intolerance of lactose monohydrate, sunset yellow aluminium lake (E110), and patients with galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
  9. 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
  10. 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
  11. 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.
  12. 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03894124
Other Study ID Numbers  ICMJE CRF001
2019-000978-33 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Chelsea and Westminster NHS Foundation Trust
Study Sponsor  ICMJE Chelsea and Westminster NHS Foundation Trust
Collaborators  ICMJE
  • Merck Sharp & Dohme Corp.
  • Imperial College London
  • University of Liverpool
Investigators  ICMJE
Principal Investigator: Marta Boffito Chelsea and Westminster Hospital NHS Foundation Trust
PRS Account Chelsea and Westminster NHS Foundation Trust
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP