- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01019824
Efficacy and Safety of Ralfinamide in Patients With Chronic Neuropathic Low Back Pain
A Phase III Study to Assess the Efficacy and Safety of Ralfinamide.
Study Overview
Detailed Description
Ralfinamide has been shown to be an effective analgesic in a number of animal models of neuropathic pain. These observed effects of ralfinamide may have been achieved by targeting both hyperactivity of peripheral sensory neurons, through voltage-dependent, Na+-channel blockade [Stummann et al., 2005] and Ca++-channel blockade, and sensitization of central neurons, through NMDA-receptor modulation.
Evidence of efficacy in mixed peripheral neuropathic pain syndromes has been demonstrated in Study 001 [Anand et al., 2008]. In particular patients with neuropathic pain due to nerve compression (e.g., compression radiculopathy, lumbar spinal stenosis, sciatic nerve compression, spinal root compression, intercostal neuralgia) showed response to ralfinamide treatment. In this sub-population, statistically significant improvements in severity of pain, as measured on the VAS and 11-point Likert scales, as well as a greater proportion of patients meeting "responder" criteria, compared to the placebo group, were noted with ralfinamide treatment. Similarly, patients in the study classified as having neuropathic low back pain also showed significant benefit from treatment with ralfinamide; therefore, the focus of the current study is on this indication.
The current study will evaluate the safety, tolerability and analgesic efficacy of ralfinamide in patients with chronic neuropathic low back pain due to nerve compression, i.e., compression radiculopathy or post-traumatic/post-surgical lumbar radiculopathy. It should also be noted that no current drug therapy has global regulatory approval for treating this type of chronic neuropathic low back pain; therefore, should ralfinamide prove effective in this patient population, it would be satisfying an unmet medical need.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
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England
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London, England, United Kingdom
- Parexel
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Patients must meet all of the following inclusion criteria to be eligible for enrolment into the study:
- Patient presents in the physical/neurological examination with low back pain with or without radiation into the lower limb that must display a topography compatible with the L1 to S1 territory and/or respective sensory or motoric impairments.
- Patient must have chronic neuropathic low back pain with a minimum intensity of "40 mm" (moderate) or greater on the Visual Analogue Scale (VAS; 100-mm) at screening, and an average of "40 mm" or more at baseline (based on prior 7 days).
- The onset of pain has occurred at least three months, but not longer than 3 years, prior to the screening visit, as assessed by the investigator in the patient's medical history.
Patient is affected by current neuropathic pain (pain provoked by a lesion of the peripheral nervous system). The diagnosis should be made by a neurologist/anaesthesiologist/pain specialist and based on history, clinical evaluation and/or laboratory findings (rule out systemic cause, e.g., hypothyroidism, rheumatoid arthritis, nephropathy, diabetes [MNSI score >2]) in accordance with the taxonomy of the diagnostic criteria documented in the International Association for the Study of Pain (IASP) Classification of Chronic Pain. A neurological disease must be directly correlated with pain, including pain due to spinal root compression.
If radiologic data supporting the diagnosis had been obtained previously it should be documented in the patient's records. In case radiologic examinations are not available, the Investigator should consider performing these examinations, if necessary to support the diagnosis, during the screening phase.
- Patient has one of the following causes of neuropathic low back pain: Non-cancer lumbar pain due to compression radiculopathy or post-traumatic/post-surgical lumbar radiculopathy.
- Patient's low back pain has a clear neuropathic component, as indicated by a rating on the Pain Detect Questionnaire (PD-Q) of greater than 18.
- Patient is 18-85 years of age, inclusive.
- Patient is willing and able to understand and sign an approved Informed Consent Form.
Exclusion Criteria:
1. Females who are pregnant or lactating, or of childbearing potential, defined as follows: surgically sterilized for less than one year; aged ≥ 50 years and post-menopausal condition started less than 24 months prior to the screening visit; or aged < 50 years and post-menopausal condition started less than 24 months prior, and/or post-menopausal status has not been confirmed by determination of the serum levels of FSH and 17-β estradiol; or fecund and not practicing double contraception method (e.g., hormonal contraceptive plus barrier method).
2. Patients with any other cause of peripheral or central neuropathic pain (including psychogenic and nociceptive pain), pain due to metabolic (including diabetes; MNSI score > 2) infectious or proliferative diseases, or pain due to any condition that is as severe as the neuropathic pain.
3. Patients with a history of migrating pain and former mononeuropathy or neuralgias in other anatomical territories.
4. Patients with severe trophic changes, severe swelling, joint deformities or stiff joint with limited passive movement, or patients who may be candidates for back surgery within 52 weeks after baseline.
5. History or current diagnosis of positive test for Hepatitis B or C (unless vaccinated).
6. Clinically significant, uncontrolled gastrointestinal, renal, hepatic, endocrine, pulmonary or cardiovascular disease (including non well-controlled hypertension), asthma, uncompensated chronic obstructive pulmonary disease (COPD), severe uncontrolled diabetes (HbA1c > 10.0).
7. Second- or third-degree atrioventricular block or sick sinus syndrome, uncontrolled atrial fibrillation, severe or unstable angina, congestive heart failure, myocardial infarction within 3 months of the screening visit, significant ECG abnormalities or QTc ≥ 450 msec (males) or ≥ 470 msec (females), where QTc is based on Bazett's correction method.
8. Concomitant disease likely to interfere with the study drug (e.g. capable of altering absorption, metabolism or elimination of drugs).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: Placebo
Placebo Comparator
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Ralfinamide Oral Tablets, 160 or 320 mg per day
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EXPERIMENTAL: Low Dose
160 mg dose
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Ralfinamide Oral Tablets, 160 or 320 mg per day
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EXPERIMENTAL: High Dose
320 mg dose
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Ralfinamide Oral Tablets, 160 or 320 mg per day
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The primary efficacy variable will be the change from baseline in the mean weekly pain score (11-point Likert scale).
Time Frame: The primary efficacy endpoint will analyze the change from baseline to Week 12 of the mean weekly pain score
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The primary efficacy endpoint will analyze the change from baseline to Week 12 of the mean weekly pain score
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Stefano Rossetti, MD, Newron Pharmaceuticals SPA
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- NW-1029/01-08
- EudraCT Nr.: 2008-006176-30 (OTHER: EMEA)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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