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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

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

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Drug: Doravirine Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single cohort pharmacokinetic (PK) study
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Pharmacokinetics of Plasma Doravirine Once Daily Over 72 Hours Following Drug Intake Cessation in Healthy Volunteers
Actual Study Start Date : June 12, 2019
Actual Primary Completion Date : July 25, 2019
Actual Study Completion Date : August 6, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Study intervention
Pifeltro® (doravirine 100mg) daily dose for 7 days
Drug: Doravirine
Non-nucleoside reverse transcriptase inhibitor. Administered as film coated tablet.
Other Name: Pifeltro




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

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): NCT03894124


Locations
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United Kingdom
Chelsea and Westminster Hospital NHS Foundation Trust
London, United Kingdom, SW10 9NH
Sponsors and Collaborators
Chelsea and Westminster NHS Foundation Trust
Merck Sharp & Dohme Corp.
Imperial College London
University of Liverpool
Investigators
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Principal Investigator: Marta Boffito Chelsea and Westminster Hospital NHS Foundation Trust

Publications:
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Responsible Party: Chelsea and Westminster NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03894124    
Other Study ID Numbers: CRF001
2019-000978-33 ( EudraCT Number )
First Posted: March 28, 2019    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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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Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases