Bioequivalence of Solid/Crushed/Dissolved Forms of Biktarvy®
Status:
Completed
Trial end date:
2021-05-31
Target enrollment:
Participant gender:
Summary
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.