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Gay Men's Health Crisis
New Saquinavir Formulation Enters Clinical Trials
Gabriel Torres, M.D.
January 1, 1996
GMHC Treatment Issues 1996 Jan 1; 10(1): 3

Hoffmann La Roche, makers of saquinavir, the first protease inhibitor to receive FDA approval for treatment of HIV infection, has just launched a large trial to test a new, more promising formulation of the drug.

The old formulation, a hard gelatin capsule with a very low bioavailability (four percent), has been used in six previous clinical trials. The drug has displayed an antiviral effect that is low in comparison to other, soon-to-be-released protease inhibitors -- at least at the standard 600 mg thrice daily dosage. A study of high doses of saquinavir (3,600 and 7,200 mg per day) done at Stanford University did show a substantial improvement in the effect on HIV levels and CD4 count.

The new trial will try the soft gelatin capsule at a dose of 1,200 mg taken three times daily, which is predicted to provide exposures to the drug similar to 7,200 mg/day with the hard gelatin capsule. The study will be double-blind and placebo-controlled (in a two to one ratio of people on saquinavir to those on placebo) for the first sixteen weeks.

Other concomitant protease inhibitors are excluded, but participants may take nucleoside analogue therapies as prescribed by their physicians. They will be required to maintain a constant anti-HIV regimen for these sixteen weeks. After the first sixteen weeks, the trial participants will be given the option of open label therapy with the soft gelatin capsule at the 1,200 mg thrice daily dose.

Six hundred volunteers are expected to be enrolled at 35 to 40 centers in the United States. They will be stratified into three groups by CD4 cell count (0 to 50, 51 to 300 and 301 to 500). One quarter of the trial group must have plasma HIV levels of greater than 20,000 copies/ml. The primary endpoints of the study will be plasma viral load by quantitative PCR and an increase in CD4 cell count. For the location of trials sites around the country, call 800/TRIALS- A.