Combination of an Investigational Cannabinoid and Methadone for HIV-associated Neuropathy

Distal sensory polyneuropathy is the most common neurological complication of HIV disease and
its treatment. To date no standard effective therapy has been identified.

In this study, scientists will evaluate the effectiveness of treating HIV-associated
neuropathy with methadone alone and in combination with a novel cannabinoid SAB378. A
cannabinoid is a molecule found only in the Cannabis plant. Cannabis and some cannabinoids
are effective analgesics or pain relievers. The rationale for combination therapy is twofold:
(1) medications with unique mechanisms of action may affect different aspects of neuropathic
pain and (2) combination therapy may act synergistically—meaning the combined effect may be
greater than the effect of each drug alone.

Approximately 84 participants will be enrolled in this double-blind, placebo-controlled,
crossover study. Participants will be randomly assigned to three treatment groups—those
receiving methadone and SAB378 placebo (an inactive substance), those receiving methadone and
active SAB378, or those receiving methadone placebo and SAB378 placebo. All participants will
be exposed to each of the 3 treatment groups during the study.

This trial is part of the Neurologic AIDS Research Consortium, an effective collaborative
clinical study group dedicated to the study of HIV-associated neurological disease.

Inclusion Criteria:

- HIV-1 infection

- HIV-associated neuropathy diagnosed by a neurologist

- Presence of at least a moderate pain score on the basis of completion of a baseline
pain diary

- Stable antiretroviral regimen for at least 8 weeks prior to study entry.

- Hemoglobin ≥ 8.0 g/dL for males and ≥ 7.5 g/dL for females

Exclusion Criteria:

- Active AIDS-defining opportunistic infection within 45 days prior to study entry

- Renal insufficiency

- Chronic liver disease

- B12 deficiency

- Family history of hereditary neuropathy

- Discontinuation of dideoxynucleoside NRTI within 16 weeks prior to entry

- On neuroregenerative therapy

- Treatment with neurotoxic drugs within 120 days prior to entry

- Respiratory compromise

- Hypotension

- Active substance abuse or dependence

- History of alcohol-related complications within 6 months prior to screening

- Women of childbearing potential