Efficacy & Safety Study of Nonracemic Methadone for the Relief of Chronic Peripheral Neuropathic Pain

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

There is a growing evidence that the d-isomer of methadone is effective in treating neuropathic pain while the l-isomer of methadone is the only effective isomer of methadone for treating somatic pain. This study will examine a combination of different amounts of the d- and l-isomers of methadone specifically tailored to the chronic peripheral neuropathic pain. Non-racemic mixture of methadone isomers will be tested in this pilot efficacy and safety study.

This study will evaluate effect of the three doses of the non-racemic mixture of methadone hydrochloride patients with chronic peripheral neuropathic pain compared with a placebo. The study will also examine the minimally effective and maximally tolerated doses of the non-racemic mixture of methadone. Finally, the safety and tolerability of the non-racemic methadone therapy will be evaluated.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: MetaPharm, Inc.
• Treatments: Methadone

Criteria

Inclusion Criteria:

• Male or female 18 years of age or older;

• Female with a negative serum βhCG pregnancy test

• Female of non-childbearing potential (postmenopausal or surgically sterile) OR female of child-bearing potential agreed to use the protocol-approved contraceptive method

• Documented diagnosis of neuropathic pain associated with diabetic peripheral neuropathy for at least 6 months

• Average daily pain severity score >=4 for the seven days prior to randomization (based on an 11-point numerical rating scale where 0= no pain and 10=worst possible pain)

• Score >= 40 mm on the VAS of the Short Form McGill Pain Questionnaire (SF-MPQ) at screening and randomization visits

• Stable doses (for at least three weeks) of non-opioid analgesics including NSAIDS, corticosteroids, gabapentin, pregabalin or antidepressants prescribed for the purposes of pain control or pain treatment naïve

• Willing to refrain from any pain-relieving drugs other than the protocol-approved rescue medications (acetaminophen, <= 3 g daily or aspirin <= 325 mg daily) during the screening phase and the course of the study

• Willing to limit alcohol consumption during the study according to protocol requirements

• Able to understand and complete study diary and questionnaires

• Willing to give informed consent prior to entry into the study

Exclusion Criteria:

• A documented neuropathy of any cause other than diabetic peripheral neuropathy

• A severe intermittent pain for reasons other than radiculopathy (e.g., migraine attacks)

• History of head injury and/or increased intracranial pressure

• Any neurologic disorder unrelated to diabetic peripheral neuropathy

• Non-adequate renal and/or hepatic function as follows: Serum creatinine > 1.5 x ULN (upper limit of normal range) Liver enzymes (ALT and AST) > 2 x ULN

• Any other know laboratory abnormality that, in the investigator's opinion, would contraindicate study participation

• Chronic hepatitis B, hepatitis C, or HIV infection

• Abnormal cognition defined as obvious clinical findings of state of arousal, confusion and memory or concentration deficit.

• Recent history (within the previous 12 months) of respiratory depression, acute bronchial asthma or hypercarbia, or any other severe pulmonary or respiratory disease

• Recent history (within the previous 12 months) of sleep apnea

• Any hemostatic disorders or a current treatment with anticoagulants;

• Unstable cardiovascular disease or symptomatic peripheral vascular disease

• Hypotension: sitting or standing systolic blood pressure <= 90 mmHg and/or diastolic blood pressure <= 60 mmHg at screening and/or orthostatic hypotension (defined as a difference between sitting and standing systolic blood pressure >20 mmHg and/or a difference between sitting and standing diastolic blood pressure >10 mmHg)

• Any clinically important ECG abnormality (including QT interval exceeding 450 ms)

• Recent history (within the last 12 months) of risk factors for development of prolonged QT interval, including cardiac hypertrophy, concomitant diuretic use, hypocalcemia, hypomagnesemia