Relative Bioavailability Study to Investigate a Potential Interaction Between DTG DT and F/TAF TOS. (UNIVERSALRBA)

December 5, 2023 updated by: Radboud University Medical Center

Relative Bioavailability Study to Investigate a Potential Interaction Between Dolutegravir (DTG) and Tenofovir Alafenamide Fumarate/Emtricitabine (F/TAF) Administered as Paediatric Tablet Formulations

This relative bioavailability (RBA) study will be conducted to investigate whether there is a potential pharmacokinetic effect when paediatric DTG and F/TAF are taken together as dispersible formulations. This study will be performed in healthy volunteers instead of HIV-infected patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This relative bioavailability (RBA) study will be conducted to investigate whether there is a potential pharmacokinetic effect when paediatric DT DTG (30 mg dose) and F/TAF TOS (180/22.5 mg dose) are taken together. For this purpose, Gilead's F/TAF 60/7.5 mg TOS tablets and ViiV Healthcare's DTG 5 mg tablets will be used. Given the very low plasma concentration of TAF (very probably mainly under the detection limit) with a single dose of 7.5 mg in adults, 3 tablets of F/TAF 60/7.5 mg (180/22.5 mg) will be given, which is similar to the adult dose. It was considered to keep the ratio between DTG and F/TAF similar to the to be developed paediatric fixed dose combination tablet, which would have resulted in a DTG dose of 60mg DTG DT. But because DTG shows nonlinear kinetics above a dose of 50 mg FCT (3), it was decided to use DTG 30 mg DT tablets, which is bioequivalent to adult dose of 50 mg FCT. For all compounds, a dose similar to the adult dose will be given.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Subject is at least 18 and not older than 55 years of age at the day of screening.
  2. Subject weighs at least 40 kg.
  3. Subject has a BMI of 18.5-30 kg/m2, extremes included.
  4. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
  5. Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry, haematology and urinalysis testing within four weeks prior to day 1. Results of biochemistry, haematology and urinalysis testing should be within the laboratory's reference ranges. If laboratory results are not within the reference ranges, the subject is included based on the Investigator's judgment that the observed deviations are not clinically relevant. This should be clearly recorded.
  6. Subject has a normal blood pressure and pulse rate, according to the Investigator's judgment.
  7. Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to day 1.

Exclusion Criteria:

  1. Positive HIV test.
  2. Positive hepatitis B or C test.
  3. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
  4. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism, or excretion.
  5. Inability to understand the nature and extent of the study and the procedures required.
  6. Pregnant female (as confirmed by an hCG test performed less than 4 weeks before day 1) or breast-feeding female. Female subjects of childbearing potential without adequate contraception, e.g., hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout the entire conduct of the study.
  7. Therapy with any drug (including herbal remedies, multivitamins, iron supplements and calcium supplements) for two weeks preceding day 1, except for acetaminophen.
  8. Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), psychiatric disorders, gastro-intestinal disorders, renal disorders (renal failure determined as an estimated Glomerular Filtration Rate (eGFR) below 50 ml/min (MDRD-based)), hepatic disorders (Child-Pugh B or C), hormonal disorders (especially diabetes mellitus), coagulation disorders.
  9. History of or current abuse of drugs, alcohol or solvents.
  10. Participation in a drug study within 60 days prior to day 1. 11. Donation of blood within 60 days prior to day 1.

12. Febrile illness within 3 days before day 1. 13. Co-worker of Radboud university medical center.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Single-dose DTG 30 mg
Healthy volunteers receiving a single-dose DTG 30 mg as 6X5 mg dispersible tablets (DT) as a dispersed suspension in a fasted state. Samples will be taken pre-dose (t=0) and 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, and 48 hours post ingestion.
Drug: DTG DT (6 x 5 mg)
DTG 5mg dispersible tablet
Other Names:
  • Tivicay 5 mg (ViiV)
Active Comparator: Single-dose F/TAF 180/22.5 mg
Healthy volunteers receiving a single-dose F/TAF 180/22.5 mg as 3X60/7.5 mg TOS as a dispersed suspension in a fasted state. Samples will be taken pre-dose (t=0) and 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, and 48 hours post ingestion.
Drug: F/TAF TOS (3 x 60/7.5 mg)
60/7.5 mg TOS emtricitabine/TAF
Other Names:
  • F/TAF TOS 60/7.5 mg (Gilead)
Experimental: Single-dose DTG 30 mg and F/TAF 180/22.5 mg
Healthy volunteers receiving a single-dose F/TAF 180/22.5 mg as 3X60/7.5 mg TOS + DTG 30 mg as 6X5 mg DT as a co-dispersed suspension in a fasted state. Samples will be taken pre-dose (t=0) and 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, and 48 hours post ingestion.
Drug: DTG DT (6 x 5 mg)
DTG 5mg dispersible tablet
Other Names:
  • Tivicay 5 mg (ViiV)
Drug: F/TAF TOS (3 x 60/7.5 mg)
60/7.5 mg TOS emtricitabine/TAF
Other Names:
  • F/TAF TOS 60/7.5 mg (Gilead)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The relative bioavailability of TAF and TFV
Time Frame: 17 days
The relative bioavailability of TAF and TFV after a single-dose F/TAF 180/22.5 mg as 3X60/7.5 mg TOS (reference TAF) compared to TAF and TFV after a single-dose F/TAF 180/22.5 mg as 3X60/7.5 mg TOS in combination with a single dose of DTG 30 mg as 6X5 mg DT tablets (test).
17 days
The relative bioavailability of FTC
Time Frame: 17 days
The relative bioavailability of FTC after a single-dose F/TAF 180/22.5 mg as 3X60/7.5 mg TOS (reference FTC) compared to FTC after a single-dose F/TAF 180/22.5 mg as 3X60/7.5 mg TOS in combination with a single dose of DTG 30 mg as 6X5 mg DT tablets (test).
17 days
The relative bioavailability of DTG
Time Frame: 17 days
The relative bioavailability of DTG after a single-dose DTG 30 mg as 6X 5 mg DT tablets (reference DTG) compared to DTG after a single-dose F/TAF 180/22.5 mg as 3X60/7.5 mg TOS in combination with a single dose of DTG 30 mg as 6X5 mg DT tablets (test).
17 days
The relative bioavailability of the potential interaction and pharmacokinetics
Time Frame: 17 days
The relative bioavailability of the potential interaction, the pharmacokinetics (AUC0-∞, Cmax, Tmax, T1⁄2) of DTG, FTC, TAF and TFV will be obtained and the geometric mean ratios of the AUC0-tlast (TAF), AUC0-∞ (DTG, FTC and TFV only), Cmax , and Cmin (DTG, FTC and TFV only) of the test versus reference treatment
17 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: 17 days
Adverse events will be described and compared (including clinically relevant laboratory abnormalities) of the treatments with F/TAF and DTG once daily.
17 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Radboud University Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Gilead Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: David Burger, Prof.dr., Radboud University Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 6, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 24, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 3, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 5, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 6, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UNIVERSAL RBA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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