Bioequivalence of Solid/Crushed/Dissolved Forms of Biktarvy®
Condition: Healthy Volunteers
MeSH terms: Crush Injuries
Study type: Interventional
Phase: Phase 1

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.
    


Intervention name(s): receive dissolved form of BIKTARVY®; receive crushed form of BIKTARVY®; receive solid form of BIKTARVY®
Intervention type(s): Drug; Drug; Drug
Intervention description(s): The healthy volunteers will receive dissolved form of BIKTARVY® Pharmacokinetic samples will be taken at the following times: 0 hour (right before taking Biktarvy®); 0.5 hour; 1 hour; 1.5 hours; 2 hours; 2.5 hours; 3 hours; 4 hours; 8 hours; 12 hours; 24 hours; 36 hours; 48 hours and 72 hours (after Biktarvy®).; The healthy volunteers will receive crushed form of BIKTARVY® Pharmacokinetic samples will be taken at the following times: 0 hour (right before taking Biktarvy®); 0.5 hour; 1 hour; 1.5 hours; 2 hours; 2.5 hours; 3 hours; 4 hours; 8 hours; 12 hours; 24 hours; 36 hours; 48 hours and 72 hours (after Biktarvy®).; The healthy volunteers will receive solid form of BIKTARVY® Pharmacokinetic samples will be taken at the following times: 0 hour (right before taking Biktarvy®); 0.5 hour; 1 hour; 1.5 hours; 2 hours; 2.5 hours; 3 hours; 4 hours; 8 hours; 12 hours; 24 hours; 36 hours; 48 hours and 72 hours (after Biktarvy®).
Other intervention name(s): no other intervention name; no other intervention name; no other intervention name
Intervention MeSH terms: Emtricitabine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment