Bioequivalence of Crushed Stribild With a Normal Breakfast or With Drip Feed Compared to the Whole Tablet
Condition: HIV
MeSH terms: Crush Injuries
Study type: Interventional
Phase: Phase 1

Summary: 
      Elvitegravir is an HIV-1 integrase inhibitor which is marketed in a fixed dose combination
      tablet with cobicistat, tenofovir and emtricitabine (Stribild®, referred to as STB). For
      patients with swallowing difficulties, administration of whole tablets can be problematic and
      tablets are cut or crushed to ease administration. In addition if HIV patients develop
      opportunistic infections, patients can become severely ill and may end up on the intensive
      care. Patients at the intensive care might not be able to swallow medication. Therefore it is
      useful to know if it is possible to administer STB through a different route, like a feeding
      tube. If STB can be crushed or dissolved and given through a catheter it is also useful to
      know if it can be given with drip feed.

      Currently there is no information about crushing STB tablets. "Crushing STB tablets into a
      liquid medium has not been studied and is not recommended" according to the SPC text.
      Depending on the biopharmaceutical characteristics of a drug formulation, crushing tablets
      can lead to altered pharmacokinetics of drugs.

      It is important to know whether pharmacokinetics are influenced by crushing of tablets as low
      concentrations are associated with virologic failure. Therefore higher doses might be needed.
      In addition, higher Cmax and/or exposure can lead to toxicity. As a result therapeutic drug
      monitoring is advised, or crushing the drug is a contra-indication based on the available
      data.

      It has been shown that simultaneous oral ingestion of antacids and elvitegravir gives a
      decrease in Cmax and AUC of elvitegravir. This interaction is not shown for co-ingestion with
      omeprazole. Which makes it unlikely that this interaction is caused by a pH-lowering effect
      influencing the absorption of elvitegravir. It is probably a local gastrointestinal
      complexation phenomenon, similar to what has been observed with other HIV integrase
      inhibitors. A possible pharmacokinetic interaction between elvitegravir and complexation
      formers may be expected. Especially considering the active binding sites of elvitegravir
      which bind magnesium metal ion cofactors. Although there is data that STB can be ingested
      with a protein rich drink, it is unclear if foods or liquids containing high amounts of
      magnesium or other cations can cause this same interaction.

      Therefore this study will be conducted to investigate whether crushed and suspended STB and
      crushed and suspended STB with drip feed are bioe-quivalent to taking STB as a whole.
    


Intervention name(s): Stribild; Stribild, crushed
Intervention type(s): Drug; Drug
Intervention description(s): Elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil; Crushed Stribild tablet
Intervention MeSH terms: Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Stribild; pharmacokinetics; Crushing; Drip feed