A Phase II/III Double-Blind Study of Amitriptyline and Mexiletine for Painful Neuropathy in HIV Infection

To assess the efficacy, safety, and tolerability of amitriptyline hydrochloride versus mexiletine hydrochloride in reducing pain intensity in patients with HIV-related painful peripheral neuropathy. No large-scale controlled clinical trials of symptomatic therapy for painful HIV-related neuropathy have been attempted. Both amitriptyline and mexiletine have been useful in the management of painful neuropathies; however, both are associated with certain toxicities. In this comparative study of amitriptyline and mexiletine, benztropine mesylate also will be included as an active placebo to mimic the side effects of the study drugs. No large-scale controlled clinical trials of symptomatic therapy for painful HIV-related neuropathy have been attempted. Both amitriptyline and mexiletine have been useful in the management of painful neuropathies; however, both are associated with certain toxicities. In this comparative study of amitriptyline and mexiletine, benztropine mesylate also will be included as an active placebo to mimic the side effects of the study drugs. Patients are randomized to receive amitriptyline, mexiletine, or benztropine mesylate as an active placebo to mimic the mild side effects associated with both amitriptyline and mexiletine. Doses are gradually increased over 4 weeks until a minimum effective dose or MTD is reached, then patients are treated for at least 4 additional weeks at the final dose before gradually tapering off. Neurologic exams are performed at screening and at the end of treatment. Intensity of pain is rated twice daily by the patient. Patients are followed at Weeks 2, 4, and 8, and at 10 days after completely tapering off of drug. PER 3/16/95 AMENDMENT: Patients with no pain relief 14 days after initiation of study therapy may have dose doubled or increased to maximum allowable dose, whichever is lower. Then if no improvement occurs within 14 days after dose increase, patients have the option of discontinuing study medication.