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

Condition(s) targeted: Diabetic Peripheral Neuropathic Pain

Intervention: Non-racemic mixture of methadone HCl (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: MetaPharm, Inc.

Official(s) and/or principal investigator(s):
Eugene Mironer, MD, Study Director, Affiliation: MetaPharm, Inc.

Overall contact:
Eugene Mironer, MD, Phone: (864) 680-4904

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.

Official title: Pilot Study to Evaluate Efficacy, Tolerability and Safety Nonracemic Methadone HCl in Patients With Chronic Peripheral Neuropathic Pain: Double-Blind, Placebo-Controlled, Crossover Study Followed by Open-Label, Single-Arm Extension

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Change in average daily pain scores

Detailed description: Objectives:

- To evaluate effect of the three doses of the non-racemic methadone HCl on the metrics

of pain intensity in comparison to placebo.

- To determine minimally effective and maximally tolerated doses of non-racemic methadone

HCl for the treatment of diabetic peripheral neuropathic pain.

- To evaluate safety and tolerability of non-racemic methadone HCl therapy.

Study Design: This is a pilot efficacy and safety study comprised of two parts. Part I is a double-blind, placebo-controlled, crossover study of three daily doses (15 mg, 30 mg and 40 mg) of non-racemic methadone compared with placebo. Two lower doses (15 mg and 30 mg) will be administered for 1 week. The final dose (40 mg) will be administered for 2 weeks. After receiving three consecutive doses of the assigned drug the subjects will be switched to another regimen. Two 28-day treatment periods will be separated by a 14-day washout (drug-free) interval. Subjects will be randomly assigned to one of the two treatment sequences: Sequence 1: non-racemic methadone HCl (Period 1) followed by Placebo (Period 2); Sequence 2: Placebo (Period 1) followed by non-racemic methadone HCl (Period 2). Subjects completing Part I will be enrolled into the open-label, single-arm extension. Subjects discontinuing the study while on placebo may also be eligible for the enrollment. During the 6-week extension phase (Part II of the study) subjects will be treated with non-racemic methadone HCl with continuous dose titration driven by the clinical response (degree of pain relief) and reported adverse events. The Parts I and II will be separated by a 14-day washout (study drug-free) interval. Number of Patients: Up to fifty (50) subjects diagnosed with neuropathic pain associated with diabetic peripheral neuropathy will be enrolled in the study; approximately 30 subjects are expected to complete Study Part I. Enrollment will be terminated when this completion target is achieved. Study Duration: The duration of Study Part I is approximately 12 weeks, the duration of Study Part II is approximately 6 weeks. A total study duration (including screening and final evaluations) is expected to be approximately 20 weeks.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Eugene Mironer, MD, Phone: (864) 680-4904

Starting date: January 2012
Last updated: September 2, 2011