Paediatric formulation of TMC 278

Polly Clayden, HIV i-Base

TMC 278 or rilpivirine is currently being evaluated for adults in a tablet formulation at a once daily dose of 25mg.

A poster at IAS2010 authored by Herta M Crauwels and colleagues showed bioavailability data from a Phase 1 trial looking at a new granule formulation intended for use in paediatric patients compared to the adult tablet formulation.

This was an open label, randomised, three way crossover trial in 12 HIV-negative adults, under both fed and fasted conditions.

Volunteers were randomised to receive:

  • Treatment A: granule formulation within 10 minutes of a standardised breakfast.
  • Treatment B: granule formulation after 10-hour overnight fast.
  • Treatment C: Tablet formulation within 10 minutes of a standardised breakfast.

The granules were dispersed in water.

Volunteers were in six groups of two and received Treatments A, B and C in six different sequences with a washout period of at least 14 days in between.

Plasma samples from a full pharmacokinetic (PK) profile were analysed for TMC278 using a validated liquid chromatography-mass spectrometry/mass spectrometry method with a lower limit of 1.0 ng/mL.

Evaluable PK parameters were available for 11 volunteers. Comparisons were made between Treatments A and B with C (reference 1), and between A (reference 2) and B for food effects on the granule formulation.

The investigators noted that plasma concentrations were quantifiable from 30 minutes post dose for the granule formulations compared to one to two hours for the tablet formulation. However the time to achieve the maximum plasma concentrations were similar between the three treatments.

They reported increases in the PK parameters with the granule formulation under both fed and fasted conditions of 18%, 28% and 26% in Cmax, AUClast and AUCinf respectively. The granule formulation under fasted conditions achieved similar exposure to tablets taken with food.

There was a decrease of 30%, 29% and 28% in exposure for the granules taken under fasted conditions compared to with food in the Cmax, AUClast and AUCinf respectively. See Table 1.

Table1: Comparing TMC 278 granules and tablet formulations LSM (95% CI)

Test Reference 1 n/n Cmax AUClast AUCinf
Relative bioavailability Granules fasted Tablet fed 11/11 1.18 (1.09-1.40) 1.28 (1.11-1.48) 1.26 (1.09-1.46)
Granules fed Tablet fed 11/11 0.87 (0.76-0.96) 0.93 (0.85-1.00) 0.93 (0.86-1.00)
Test Reference 2 n/n Cmax AUClast AUCinf
Food effect Granules fasted Granules
11/11 0.70 (0.59-0.83) 0.71 (0.63-0.80) 0.72 (90.64-0.81)

In a taste questionnaire 10/12 volunteers rated the granules “acceptable” or “good”. The investigators noted that all treatments were generally well tolerated and no new safety signals were observed.

They concluded that the TMC 278 granule formulation has good oral biovailability and palatability and will be developed further for use in paediatric trials.


Crauwels HM et al. Relative bioavailability of a concept paediatric formulation of TMC278, an investigational NNRTI. 18th IAS Conference, 18–23 July 2010, Vienna. Abstract THPE0158.

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