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

NCT ID: NCT03894124

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-12
• Study Completion Date: 2019-08-06

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.

Conditions

Human Immunodeficiency Virus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Study intervention

Pifeltro® (doravirine 100mg) daily dose for 7 days

Group Type: OTHER

Doravirine

Intervention Type: DRUG

Non-nucleoside reverse transcriptase inhibitor. Administered as film coated tablet.

Interventions

Doravirine

Non-nucleoside reverse transcriptase inhibitor. Administered as film coated tablet.

Intervention Type: DRUG

Other Intervention Names

Pifeltro

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: collaborator

University of Liverpool

OTHER

Sponsor Role: collaborator

Chelsea and Westminster NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marta Boffito

Role: PRINCIPAL_INVESTIGATOR

Chelsea and Westminster NHS Foundation Trust

Locations

Chelsea and Westminster Hospital NHS Foundation Trust

London, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 30272231 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30047107 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2019-000978-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRF001

Identifier Type: -

Identifier Source: org_study_id