The Safety and Efficacy of Combination N-Butyl-Deoxynojirimycin (SC-48334) and Zidovudine in Patients with HIV-1 Infection and 200–500 CD4 Cells/mm

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We conducted a double-blind. randomized phase II study to evaluate the safety and activity of combination therapy with N-deoxynojirimycin (SC-48334) (an α-glucosidase I inhibitor) and zidovndine versus zidovudine alone. Patients with 200 to 500 Cl)4 cells mm3 who tolerated −12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h and zidovudine ( 100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58. zidovudine and placebo. Twenty-three patients (38%) and 15 (26%). in the combination and zidovudine groups, respectively. discontinued therapy (p - 0.15). The mean SC-48334 steady-state trough level (4.04 ± 0.99 μ.g ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells mm3 and 52.4 cells mm3 for the combination and zidovudine groups, respectively (p - 0.36). lor patients with prior zidovudine therapy. the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells mm3 and 4.9 cells mm3 at week 8 and 6.8 cells mm3 and 45.1 cells mm3 at week 16. respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p - 0.10) and five (45%) and two (14%) at week 24 (p - 0.08). respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients. Although superiority of combination therapy was not seen, these data suggest that SC-48334 has anti-HIV activity and provide a rationale for the evaluation of better tolerated compounds of this class.

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