A Phase I Concentration-Targeted Multidose Study of Atevirdine Mesylate ( U-87201E ), AZT, and ddI or ddC

Summary

To determine the safety, toxicity, pharmacokinetic profile, and antiretroviral activity of atevirdine mesylate ( U-87201E ) in HIV-infected patients. Per 06/04/93 amendment, to also evaluate the interactive effects of didanosine ( ddI ) or zalcitabine ( dideoxycytidine; ddC ) with zidovudine ( AZT ) on the pharmacokinetics of U-87201E and to assess the effects of the triple combination therapies on immunologic and virologic parameters. Since the use of non-nucleoside reverse transcriptase inhibitors such as U-87201E has been associated with the rapid development of resistant HIV isolates, an initial evaluation of this drug in patients was made in combination with AZT. Because of the inability to detect resistance after 6 weeks of combined AZT/U-87201E therapy, this protocol will initially investigate U-87201E administered alone and then investigate the effect of this drug with AZT and ddI or ddC.

Timeline

Start

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Primary completion

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Completion

1995-02

Publications

• Background Demeter LM, Meehan PM, Morse G, Fischl MA, Para M, Powderly W, Leedom J, Holden-Wiltse J, Greisberger C, Wood K, Timpone J Jr, Wathen LK, Nevin T, Resnick L, Batts DH, Reichman RC. Phase I study of atevirdine mesylate (U-87201E) monotherapy in HIV-1-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Oct 1;19(2):135-44. doi: 10.1097/00042560-199810010-00006.
• Background Morse GD, Reichman RC, Fischl MA, Para M, Leedom J, Powderly W, Demeter LM, Resnick L, Bassiakos Y, Timpone J, Cox S, Batts D. Concentration-targeted phase I trials of atevirdine mesylate in patients with HIV infection: dosage requirements and pharmacokinetic studies. The ACTG 187 and 199 study teams. Antiviral Res. 2000 Jan;45(1):47-58. doi: 10.1016/s0166-3542(99)00073-x.

Drugs

Indications