NCT04244448: SOLUBIC

Bioequivalence of Solid/Crushed/Dissolved Forms of Biktarvy®

Completed Phase 1 Last updated 28 July 2021

What this trial tests

Phase 1 trial testing receive dissolved form of BIKTARVY® in Healthy Volunteers in 18 participants. Completed in 31 May 2021.

Timeline

2 December 2019

Primary endpoint
24 April 2021

31 May 2021

Quick facts

Lead sponsor	University Hospital, Caen
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	treatment
Enrollment	18
Start date	2 December 2019
Primary completion	24 April 2021
Estimated completion	31 May 2021
Sites	1 location across France

Drugs / interventions tested

• receive dissolved form of BIKTARVY® — full drug profile →
• receive crushed form of BIKTARVY® — full drug profile →
• receive solid form of BIKTARVY® — full drug profile →

Conditions studied

• Healthy Volunteers — all drugs for Healthy Volunteers →

Sponsor

University Hospital, Caen

Who can join

Adults 18 to 55, any sex, with Healthy Volunteers. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Study context:

Some HIV-positive patients have difficulties with oral administration of antiretroviral drugs, such as children and adults suffering from ENT cancer. It is therefore necessary to offer these patients an alternative: administering the triple therapy in a liquid or well crushed form would be alternatives to a solid tablet, conditional on demonstrating their bioequivalence and that they are well tolerated (taste in particular).

Objectives:

The investigator's primary intention is to demonstrate the bioequivalence of each of the three active ingredients in Biktarvy® (single daily tablet made up of a set combination of tenofovir alafenamide/emtricitabine/bictegravir: TAF/FTC/BIC) by administering the drug in the forms of a complete and solid tablet (phase S), a tablet dissolved in water (phase D) or a tablet crushed and suspended in apple compote (phase C). The secondary objectives are to compare the safety, tolerance (taste in particular) and preference of healthy volunteers after administration of Biktarvy®, depending on the three methods of oral administration.

Equipment and methods:

This is a phase I, monocentric, open, three-period, randomised, cross-over trial that will be conducted with 18 healthy volunteers (9 men, 9 women) above the age of 18 in a French university hospital (Caen University Hospital - CHU de Caen). The healthy volunteers will be randomised to receive three different forms (solid, dissolved or crushed) in a varying order, according to the randomisation, at an interval of 14 to 28 days. After each of the three doses, the volunteers will be hospitalised for 24 hours and will then return three times to carry out the pharmacokinetic study with samples taken at the following times: 0 h (right before taking Biktarvy®); 0.5 h; 1 h; 1.5 h; 2 h; 2.5 h; 3 h; 4 h; 8 h; 12 h; 24 h; 36 h; 48 h and 72 h (after Biktarvy®).

The plasma concentration in antiretroviral drugs will be analysed by liquid chromatography-mass spectrometry (QTRAP 5500, Sciex, Les Ulis, France) at Orléans Regional Hospital (CHR d'Orléans). The bioequivalence between administration methods D or C will be demonstrated if the confidence interval at 90% (CI 90%) of the ratio parameters Cmax, AUC0-72h and AUC0-∞ is included in the 80%-125% range of those obtained for administration method S and for the three active ingredients.

Hypothesis tested:

Oral administration of Biktarvy® tablets dissolved in water (as a liquid solution) or crushed and administered in an apple compote is bioequivalent to the solid form (entire tablet swallowed with water) with regard to the three active ingredients that make up Biktarvy®. This means that these methods could be offered to patients who have difficulties with swallowing tablets. Preliminary data must be obtained using healthy volunteers.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Bioavailability of dissolved and crushed single tablets of bictegravir, emtricitabine, tenofovir alafenamide in healthy adults: the SOLUBIC randomized crossover study.
   Hocqueloux L, Lefeuvre S, Bois J, Brucato S, et al · · 2022 · cited 12× · PMID 36322475 · DOI 10.1093/jac/dkac369