Bioequivalence of Crushed Stribild With a Normal Breakfast or With Drip Feed Compared to the Whole Tablet
Status:
Completed
Trial end date:
2015-02-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 1
Details
Lead Sponsor:
Radboud University
Treatments:
Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination