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

NCT03894124 | Completed Phase 1 Results

• 2 other identifiers: CRF0012019-000978-33
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Conditions

Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (4)

• 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. Blood samples were collected pre-dose and at 2, 4, 8, 12, 24, 30, 36, 48, 60 and 72 h post-dose

  72 hours from treatment cessation; days 7-10 inclusive from enrolment

• Steady State Plasma Concentrations of Doravirine After Drug Intake Cessation up to 72h Post-dose

  Following cessation of daily dorovirine, plasma concentrations of drug to be taken before last dose and at 11 further timepoints over 72 hours. Blood samples were collected at pre-dose and at 2,4,8,12,24,30,36,47,60 and 72h post-dose

  72 hours from treatment cessation; days 7-10 inclusive from enrolment

• Steady State Plasm Concentrations of Doravirine After Drug Intake Cessation up to 72 Hours Post-dose

  Following cessation of daily dorovirine, plasma concentrations of drug to be taken before last dose and at 11 further timepoints over 72 hours. Blood samples were collected pre-dose and at 2, 4, 8, 12, 24, 30, 36, 48, 60 and 72h post-dose

  72 hours from treatment cessation; days 7-10 inclusive from enrolment

• Steady State Plasma Concentrations of Doravirine After Drug Intake Cessation up to 72 Hours Post-dose.

  Following cessation of daily dorivirine, plasm concentrations of drug to be taken were collected pre-dose and at 2,4,8, 12, 24, 30, 36, 48, 60 and 72h post-dose

  72 hours from treatment cessation; days 7-10 inclusive from enrolment

Secondary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events

  From enrolment to last visit; last visit will be between days 20-23 from enrolment

Study Arms (1)

Study intervention

OTHER

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

Drug: Doravirine

Interventions

Doravirine DRUG

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

Also known as: Pifeltro

Study intervention

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chelsea and Westminster NHS Foundation Trust: lead
• Merck Sharp & Dohme LLC: collaborator
• Imperial College London: collaborator
• University of Liverpool: collaborator

Study Sites (1)

Chelsea and Westminster Hospital NHS Foundation Trust

London, SW10 9NH, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 30272231 BACKGROUND

• 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.

  PMID: 30047107 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

doravirine

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Research Operations Manager
• Organization: Chelsea and Westminster NHS Foundation Trust

chelwest.research@nhs.net

+442033156825

Study Officials

• Marta Boffito

  Chelsea and Westminster NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single cohort pharmacokinetic (PK) study

Study Record Dates

• First Submitted: March 26, 2019
• First Posted: March 28, 2019
• Study Start: June 12, 2019
• Primary Completion: July 25, 2019
• Study Completion: August 6, 2019
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)