Human Immunodeficiency VirusPhase 1NCT03894124

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

A Phase 1 study testing Doravirine in people with Human Immunodeficiency Virus, run by Chelsea and Westminster NHS Foundation Trust at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Study to assess the pharmacokinetics of plasma doravirine once daily over 72 hours following drug intake cessation at steady-state in healthy volunteers Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Human Immunodeficiency Virus
What is being tested?: Doravirine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 1 siteUnited Kingdom
Study dates: 12 Jun 2019to 6 Aug 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

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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

Who cannot join

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

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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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Chelsea and Westminster Hospital NHS Foundation Trust
London, SW10 9NH

Other trials in United Kingdom

About this study

Study to assess the pharmacokinetics of plasma doravirine once daily over 72 hours following drug intake cessation at steady-state in healthy volunteers

Read the 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
Being tested: Doravirine
Medical subject headings: Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DoravirineDrug
Also called Pifeltro
Non-nucleoside reverse transcriptase inhibitor. Administered as film coated tablet.

Study groups in NCT03894124
Study group	Role	What they receive
Study intervention	Other	Pifeltro® (doravirine 100mg) daily dose for 7 days Receives: Drug: Doravirine

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (1)

Number of Participants With Treatment-emergent Adverse Events
All adverse events to be recorded and reported during the study up to last visit.
Measured: From enrolment to last visit; last visit will be between days 20-23 from enrolment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Jun 20196 Aug 2019

First posted28 Mar 2019
Study start12 Jun 2019
Primary completion25 Jul 2019
Study completion6 Aug 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Human Immunodeficiency VirusStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Model description: Single cohort pharmacokinetic (PK) study
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03894124
Sponsor's protocol ID: CRF001
Other IDs: 2019-000978-33, 2019
Status last verified: Sep 2024
First submitted: 26 Mar 2019
Last updated: 19 Sep 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 30272231
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.
PubMed 30047107

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Human Immunodeficiency Virus trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacokinetics of Plasma Doravirine Once Daily Over 72 Hours Following Drug Intake Cessation in Healthy Volunteers
ClinicalTrials.gov ID: NCT03894124
Acronym / sponsor ID: CRF001
Conditions: Human Immunodeficiency Virus
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Chelsea and Westminster NHS Foundation TrustUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC, Imperial College London, University of Liverpool
Study start: 12 Jun 2019 (actual)
Primary completion: 25 Jul 2019 (actual)
Study completion: 6 Aug 2019 (actual)
First posted: 28 Mar 2019 (actual)
Results: Posted 19 Sep 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 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:

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Single cohort pharmacokinetic (PK) study

Arm	Type	Receives
Study intervention	Other	Drug: DoravirinePifeltro® (doravirine 100mg) daily dose for 7 days

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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.

Key exclusion criteria (12 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DoravirineAlso: PifeltroNon-nucleoside reverse transcriptase inhibitor. Administered as film coated tablet.	Drug	Study intervention

Primary outcome

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. Blood samples were collected pre-dose and at 2, 4, 8, 12, 24, 30, 36, 48, 60 and 72 h post-dose
Steady State Plasma Concentrations of Doravirine After Drug Intake Cessation up to 72h Post-dose
Time frame: 72 hours from treatment cessation; days 7-10 inclusive from enrolment
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
Steady State Plasm 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 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
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 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

1 secondary outcome

Number of Participants With Treatment-emergent Adverse Events
Time frame: From enrolment to last visit; last visit will be between days 20-23 from enrolment

Results and safety

Results posted to the registry on 19 Sep 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Study Intervention	14	14

Primary outcome: 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. Geometric mean (95% Confidence Interval). Unit: ng*hr/mL

Measure	Study Intervention n = 14
Doravirine steady-state PK parameters measured over 24h AUC 0-24h	18354 (16395 to 21410)
Doravirine steady-state PK parameters measured over 24h AUC 0-72h	26338 (23080 to 31743)

Population analysed: Plasma concentrations of doravirine after drug intake cessation up to 72 hours post-dose were investigated in population of participants for the study

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

Time frame: 72 hours from treatment cessation; days 7-10 inclusive from enrolment. Geometric mean (95% Confidence Interval). Unit: ng*hr/mL

Measure	Study Intervention n = 14
Cmax 0-24h	1286 (1162 to 1488)
Cmax 0-72h	1286 (1188 to 1462)

Population analysed: Plasma concentrations of doravirine after drug intake cessation up to 72 hours post-dose were investigated in population of participants for the study

Primary outcome: Steady State Plasm 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. Geometric mean (95% Confidence Interval). Unit: ng*hr/mL

Measure	Study Intervention n = 14
Ctrough at 24 h	420 (373 to 526)
Ctrough at 72 h	39 (33 to 61)

Population analysed: Plasma concentrations of doravirine after drug intake cessation up to 72 hours post-dose were investigated in population of participants for the study

Primary outcome: 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. Geometric mean (95% Confidence Interval). Unit: ng*hr/mL

Measure	Study Intervention n = 14
t1/2 0-24h	14.56 (13.19 to 16.59)
t1/2 0-72h	13.97 (12.77 to 15.68)

Population analysed: Plasma concentrations of doravirine after drug intake cessation up to 72 hours post-dose were investigated in population of participants for the study

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Safety and tolerability of the studied drug was collected over a period of 23 days.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Study Intervention	0 of 14 (0%)	6 of 14 (42.9%)	0 of 14

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 30272231Elliot 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.
Background: PubMed 30047107Wilby 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Marta Boffito principal investigator

Chelsea and Westminster NHS Foundation Trust

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Doravirine in people with Human Immunodeficiency Virus, run by Chelsea and Westminster NHS Foundation Trust at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03894124, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.