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

Diabetic Peripheral Neuropathic Pain Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01429181
• Other study ID #: MP10-001
• Status: Completed
• Phase: Phase 2
• First received: August 31, 2011
• Last updated: March 28, 2017
• Start date: January 2012
• Est. completion date: December 2014

Study information

• Verified date: March 2017
• Source: MetaPharm, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: December 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female 18 years of age or older;

• Female with a negative serum ßhCG 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

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Diabetic Peripheral Neuropathic Pain
• Neuralgia

Intervention

Drug:
• Non-racemic mixture of methadone HCl
Non-racemic mixture of methadone HCl capsules, 5 mg

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
MetaPharm, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in average daily pain scores		From Baseline to Week 4