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

NCT05489406 | Completed Phase 1

• 1 other identifier: UNIVERSAL RBA
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hiv

Outcome Measures

Primary Outcomes (4)

• The relative bioavailability of TAF and TFV

  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

  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

  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

  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 Outcomes (1)

• Adverse events

  17 days

Study Arms (3)

Single-dose DTG 30 mg

ACTIVE COMPARATOR

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)

Single-dose F/TAF 180/22.5 mg

ACTIVE COMPARATOR

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)

Single-dose DTG 30 mg and F/TAF 180/22.5 mg

EXPERIMENTAL

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); Drug: F/TAF TOS (3 x 60/7.5 mg)

Interventions

DTG DT (6 x 5 mg) DRUG

DTG 5mg dispersible tablet

Also known as: Tivicay 5 mg (ViiV)

Single-dose DTG 30 mg; Single-dose DTG 30 mg and F/TAF 180/22.5 mg

F/TAF TOS (3 x 60/7.5 mg) DRUG

60/7.5 mg TOS emtricitabine/TAF

Also known as: F/TAF TOS 60/7.5 mg (Gilead)

Single-dose DTG 30 mg and F/TAF 180/22.5 mg; Single-dose F/TAF 180/22.5 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is at least 18 and not older than 55 years of age at the day of screening.
• Subject weighs at least 40 kg.
• Subject has a BMI of 18.5-30 kg/m2, extremes included.
• Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
• 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.
• Subject has a normal blood pressure and pulse rate, according to the Investigator's judgment.
• Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to day 1.

You may not qualify if:

• Positive HIV test.
• Positive hepatitis B or C test.
• Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
• Relevant history or current condition that might interfere with drug absorption, distribution, metabolism, or excretion.
• Inability to understand the nature and extent of the study and the procedures required.
• 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.
• Therapy with any drug (including herbal remedies, multivitamins, iron supplements and calcium supplements) for two weeks preceding day 1, except for acetaminophen.
• 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.
• History of or current abuse of drugs, alcohol or solvents.
• Participation in a drug study within 60 days prior to day 1. 11. Donation of blood within 60 days prior to day 1.
• \. Febrile illness within 3 days before day 1. 13. Co-worker of Radboud university medical center.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Gilead Sciences: collaborator

Study Sites (1)

RTCCS Radboudumc

Nijmegen, Netherlands

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

dolutegravir

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

Study Officials

• David Burger, Prof.dr.

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2022
• First Posted: August 5, 2022
• Study Start: October 6, 2022
• Primary Completion: March 24, 2023
• Study Completion: November 30, 2023
• Last Updated: December 6, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)