Study of D-Methadone in Patients With Chronic Pain

• d-Methadone (Drug): 8 subjects to receive 40 mg d-Methadone twice a day
• D-methadone (Drug): After randomization, patients will take the study drug or placebo for 12 days and then they will cross-over to the opposite arm for another 12 days. The study will end on day 24.
• placebo (Drug): After randomization, patients will take the study drug or placebo for 12 days and then they will cross-over to the opposite arm for another 12 days. The study will end on day 24.

Primary outcomes

• Number Who Reached a Safe Dose [2 years]: The number of patients who reached a safe and well tolerated dose of d-methadone

Sex: All, ages: 18 Years to any

Inclusion Criteria:

Phase I and Phase II portions of the study:

* 18 years of age or older
* Chronic pain with average 24 hour intensity rated at least 3 on a verbal numerical scale from 0-10 during the 24 hours prior to study entry.
* Give informed consent to participate in this study.
* Karnofsky Performance Score (KPS) >= to 80
* Negative urine pregnancy test, verified by the study nurse, at study entry (for women of child-bearing potential). Patients must also use a medically approved contraceptive method during the study period.

Phase I only:

* Responsible companion living with patient during study.

Phase II only:

* Group 1 -- Patients must be taking chronic opioid therapy (long acting morphine, long acting oxycodone, transdermal fentanyl) at a stable dose for a minimum of four days. The dose of as needed short acting opioid does not need to be stable.
* Group 2 -- Patients must not be receiving opioids and must have cancer related neuropathic pain secondary to post-chemotherapy peripheral neuropathy, post-radiation and/or post surgical plexopathy, radiculopathy or neuropathy, or post- herpetic neuralgia.

Exclusion Criteria:

Phase I and Phase II:

* Known hypersensitivity to methadone
* Patient taking methadone or with a history of methadone treatment within one month of study enrollment.
* Patient that requires changes in the dose of one of the following medications within 2 weeks of study enrollment:

  * Abacavir,
  * Benzodiazepines,
  * Carbamazepine,
  * Efavirenz,
  * Fluconazole,
  * Fluvoxamine,
  * FOS amprenavir,
  * Fosphenytoin,
  * Naltrexone,
  * Nelfinavir,
  * Nevirapine,
  * Phenytoin,
  * Rifampin,
  * Rifapentine,
  * Risperidone,
  * Ritonavir,
  * St. John's Wort,
  * Zidovudine
* Hepatic function tests (SGOT, alkaline phosphatase, bilirubin) greater than 2 times the upper limit of normal or creatinine greater than 1.4 within 30 days of study entry.
* Neurologic or psychiatric disease sufficient, in the investigator's opinion, to compromise data collection.
* Women who are pregnant or nursing.
* Women of childbearing potential who do not agree to use a medically recognized method of contraception during the study period.

Participant flow

Outcome results

• Number Who Reached a Safe Dose (Primary), Number, participants: Phase I, Cohort l 8

Adverse events

Serious adverse events by term

Other adverse events by term

• Natalie Moryl, MD, Principal investigator, Memorial Sloan Kettering Cancer Center