Bioequivalence Study of CRushed TriUMeq With or Without Drip Feed Compared to the Whole Tablet — SCRUM  

HIV Clinical Trial

Official title: Bioequivalence Study of CRushed TriUMeq With or Without Drip Feed Compared to the Whole Tablet (SCRUM)

Status Completed

Clinical Trial Summary

Dolutegravir is an HIV-1 integrase inhibitor which is marketed as a single tablet (Tivicay®) and in a fixed dose combination tablet with abacavir and lamivudine (Triumeq®, referred to as TRI). For patients with swallowing difficulties, administration of whole tablets can be problematic and tablets are cut or crushed to ease administration.

Currently there is no information about crushing TRI tablets. Therefore this study will be conducted to investigate whether crushed and suspended TRI and crushed and suspended TRI with drip feed are bioequivalent to taking TRI as a whole.

Clinical Trial Description

Dolutegravir is an HIV-1 integrase inhibitor which is marketed as a single tablet (Tivicay®) and in a fixed dose combination tablet with abacavir and lamivudine (Triumeq®, referred to as TRI). 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 TRI through a different route, like a feeding tube. If TRI 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 TRI tablets. Depending on the biopharmaceutical characteristics of a drug formulation, crushing tablets can lead to altered pharmacokinetics of drugs. This has been shown for some of the antiretroviral drugs, such as ritonavir, lopinavir, efavirenz and tenofovir.

It is important to know whether pharmacokinetics are influenced by crushing of tablets as low concentrations are associated with virologic failure. Therefore higher doses or switching to other HIV-drugs 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 DTG plasma concentration is influenced by food, with higher AUC en Cmax after a high-fat meal compared to administration in a fasted state. During clinical development, however, dolutegravir intake was studied without regard to food intake. Therefore, it is recommended that dolutegravir can be taken with or without food.

In addition, it has been shown that simultaneous oral ingestion of antacids and dolutegravir gives a decrease in Cmax and AUC of dolutegravir. 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 dolutegravir. It is probably a local gastrointestinal complexation phenomenon, similar to what has been observed with other HIV integrase inhibitors. A possible pharmacokinetic interaction between dolutegravir and complexation formers may be expected. Especially considering the active binding sites of dolutegravir which bind magnesium metal ion cofactors. It is currently unclear if certain foods or liquids containing high amounts of magnesium or other cations, like drip feed, can cause this same interaction.

Therefore this study will be conducted to investigate whether crushed and suspended TRI and crushed and suspended TRI with drip feed are bioequivalent to taking TRI as a whole. ;

Related Conditions & MeSH terms

• Crush Injuries
• HIV

• NCT number: NCT02569346
• Study type: Interventional
• Source: Radboud University
• Status: Completed
• Phase: Phase 1
• Start date: March 2016
• Completion date: May 2016