About The Study
Compare the safety and efficacy of the new protease inhibitor amprenavir (APV) with the licensed protease inhibitor indinavir (IDV), each in combination with nucleoside reverse transcriptase inhibitor (NRTI) therapy.
Study Approach
This was a multicentre, open-label, phase III study where adult participants with a viral load above or equal to 400 copies/ml were randomized to receive amprenavir 1200 mg twice daily or indinavir 800 mg three times daily, each given in combination with two NRTIs. Volunteers had to have received nucleoside therapy (AZT, ddI, ddC, 3TC or d4T) for at least 12 weeks and have never received a protease inhibitor. They were encouraged to change their background NRTI therapy when they entered the study, and were eligible to change their randomized treatment if the switch criteria as specified in the protocol were met. Participants were stratified by screening viral load and whether or not a change in NRTI therapy was planned at the onset.
Study population
A total of 504 participants were enrolled in the study. The demographics and characteristics were similar for the two study groups. At the onset, the median viral load was 3.87 log10 copies in the APV group and 3.98 log10 copies/ml in the IDV group. The median CD4 counts were 389 and 414 respectively. On Day 1 of the study, the most commonly used NRTI combinations were either stavudine/lamivudine or stavudine/didanosine. The majority of participants in both treatment arms had more than one year of prior NRTI experience.
Results
Safety: By Week 48, 18% of the APV recepients versus 15% of the IDV recipients had permanently discontinued randomized therapy due to an adverse event. More subjects in the APV group discontinued early due to gastrointestinal symptoms, whereas more subjects in the IDV group discontinued later due to urological symptoms. The maximum intensity of any event was mild to moderate in the majority of participants in each group. About 3% of the participants receiving APV reported events related to abnormal fat redistribution compared to 12% of the participants receiving IDV.
Efficacy: In the intent to treat analysis, the treatment success (viral load below 400 copies/ml) after 48 weeks was achieved in 30% of the APV recipients versus 46% of the IDV recipients. In the APV group, 26% either had a viral load equal to or above 400 copies/ml at Week 48 or had discontinued randomized therapy prior to Week 48 for this reason (had “true failures”), versus 18% in the IDV group.
Conclusions
Both drugs had a favourable safety profile through forty-eight weeks therapy but they also had a distinct adverse event profile (see results). The efficacy intent to treat analysis showed a balance in favour of indinavir. This balance was influenced by a higher discontinuation rate in the amprenavir group. The open label design of the study may have led to biases in treatment discontinuation and adherence with study therapy.
Note: These results were provided by GlaxoSmithKline.