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

Inclusion Criteria

Concurrent Medication:

Allowed:

• Aspirin and acetaminophen.
• Nonsteroidal anti-inflammatory agents.
• Opiates.
• Pyridoxine (only if accompanied by isoniazid).
• ddI, ddC, d4T, and 3TC if on a stable dose.
• AZT.
• Cimetidine if on a stable dose.

NOTE:

• Per 3/16/95 amendment, Lactaid may be taken by lactose-intolerant patients for effects of lactose in placebo capsules.

Concurrent Treatment:

Allowed:

• Acupuncture.

Patients must have:

• Documented HIV infection.
• Painful peripheral neuropathy.

NOTE:

• Patients in ACTG blinded studies of dideoxynucleosides such as ddI, ddC, and d4T are encouraged to enroll in this study.

Prior Medication:

Allowed:

• Prior ddI, ddC, d4T, or 3TC, if on a stable dose for at least 8 weeks prior to study entry.
• Prior cimetidine if on a stable dose for at least 2 weeks prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Diabetes mellitus.
• Neurological disease of sufficient severity to confound the evaluation of peripheral neuropathy, such as myelopathy without neuropathy. (NOTE: Patients with both myelopathy AND painful peripheral neuropathy are eligible.)
• Electrocardiogram (EKG) indicating malignant arrhythmia or cardiac conduction disturbances (such as second or third degree AV block, anterior hemi-block, or prolonged QT interval).
• Suicidal thoughts of sufficient severity to require treatment with antidepressant medication.

Concurrent Medication:

Excluded:

• Phenytoin or carbamazepine (unless on stable dose for 8 weeks prior to study entry).
• Capsaicin.
• Any MAO inhibitor antidepressants, any tricyclic or tetracyclic antidepressants, certain serotonin re-uptake inhibitors (fluoxetine, paroxetine, and venlafaxine), or mexiletine (except as dispensed for this study).
• Disopyramide.
• Procainamide.
• Quinidine.
• Tocainide.
• Flecainide acetate.
• Encainide.
• Lidocaine.
• Cisplatin.
• Vincristine.
• Chloramphenicol, disulfiram, ethionamide glutethimide, gold, hydralazine, iodoquinol, metronidazole, nitrofurantoin, or ribavirin (only in patients in whom the onset or clear worsening of painful peripheral neuropathy was attributed to previously taking these drugs).
• Any investigational drugs other than 3TC (except with permission of the protocol team).
• Terfenadine (if concurrent with ketoconazole).

Patients with the following prior conditions are excluded:

• Documented history of cardiac disease.
• History of allergy to, or intolerance of, tricyclic antidepressants, mexiletine, or benztropine.

Prior Medication:

Excluded:

• Prior disopyramide.
• Prior procainamide.
• Prior quinidine.
• Prior tocainide.
• Prior flecainide acetate.
• Prior encainide.
• Prior lidocaine.
• Cisplatin or vincristine within 8 weeks prior to study entry.
• Chloramphenicol, disulfiram, ethionamide glutethimide, gold, hydralazine, iodoquinol, metronidazole, nitrofurantoin, or ribavirin within 8 weeks prior to study entry (only in patients in whom the onset or clear worsening of painful peripheral neuropathy was attributed to taking these drugs).
• Any MAO inhibitor antidepressants, any tricyclic or tetracyclic antidepressants, certain serotonin re-uptake inhibitors (fluoxetine, paroxetine, and venlafaxine), or mexiletine, within 4 weeks prior to study entry.
• More than 50 percent change in the weekly dosage of any pain control medications within 2 weeks prior to study entry.

Per 3/16/95 amendment:

• ddI, ddC, d4T, or 3TC within 8 weeks prior to study entry ONLY IF dideoxynucleoside dosing was suspended or permanently discontinued.

Risk Behavior:

Excluded:

• Active drug or alcohol abuse.

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety