Study of D-Methadone in Patients With Chronic Pain

Study Overview
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Brief Summary
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The purpose of this study is to determine the safest dose of d-methadone that can be given, without causing severe side effects in most patients with chronic pain. Patients are being asked to participate in the Phase I portion of this study.

Official Title
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A Phase I/II Study of D-Methadone in Patients With Chronic Pain

Conditions
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Pain, Bladder Cancer, Breast Cancer, CNS Cancer, Colon Cancer, Esophageal Cancer, Pancreatic Cancer, Prostate Cancer, Uterine Cancer, Head and Neck Cancer, Eye Cancer, Otorhinolaryngologic Neoplasms

Intervention / Treatment
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* Drug: d-Methadone
* Drug: D-methadone
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I, Group<br>This is an open label dose-ranging trial. The first cohort of 8 patients will receive 40mg of d-methadone every 12 hours. | Drug: d-Methadone<br>* 8 subjects to receive 40 mg d-Methadone twice a day<br>|
| Experimental: Phase II, Group I<br>patients receiving around the clock opioid therapy-No patients were accrued to this group | Drug: D-methadone<br>* 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.<br>|
| Experimental: Phase II, Group II<br>patients not receiving around the clock opioid therapy.No patients were accrued to this group | Drug: placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Who Reached a Safe Dose | The number of patients who reached a safe and well tolerated dose of d-methadone | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, HEENT cancer