PainPhase 3NCT01019824
Efficacy and Safety of Ralfinamide in Patients With Chronic Neuropathic Low Back Pain
A Phase 3 study testing Ralfinamide in people with Pain, run by Newron Pharmaceuticals SPA at 1 site in United Kingdom.
Trial summary
The aim of the study is to determine if an experimental drug, ralfinamide, relieves your neuropathic low back pain, and if it demonstrates superiority to placebo, a "dummy" or sugar pill that contains no active medication. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Pain
- What is being tested?
- Ralfinamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 411 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Mar 2009to 9 Aug 2011
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase III Study to Assess the Efficacy and Safety of Ralfinamide.
The aim of the study is to determine if an experimental drug, ralfinamide, relieves your neuropathic low back pain, and if it demonstrates superiority to placebo, a "dummy" or sugar pill that contains no active medication. Ralfinamide, given as either 160 mg/day or 320 mg/day, taken in a divided dose twice-a-day, will be compared with placebo. If you are randomly (by chance) selected to receive placebo, you will receive this medication throughout the treatment period of the study. Data from this study will provide essential information for choosing the doses of ralfinamide to be used in the treatment of this type of pain and potentially other types of pain.
Read the 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.
- Conditions
- Pain
- Being tested
- Ralfinamide
- Keywords
- nerve compression, compression radiculopathy, post-traumatic/post-surgical lumbar radiculopathy
- Medical subject headings
- Pain, Neuroma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RalfinamideDrug
Ralfinamide Oral Tablets, 160 or 320 mg per day
| Study group | Role | What they receive |
|---|---|---|
| Low Dose | Experimental | 160 mg dose Receives: Drug: Ralfinamide |
| High Dose | Experimental | 320 mg dose Receives: Drug: Ralfinamide |
| Placebo | Placebo comparator | Placebo Comparator Receives: Drug: Ralfinamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary efficacy variable will be the change from baseline in the mean weekly pain score (11-point Likert scale).
Measured: The primary efficacy endpoint will analyze the change from baseline to Week 12 of the mean weekly pain score
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2009 (estimated)
- Study start20 Mar 2009
- Primary completion11 May 2010
- Study completion9 Aug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 411 participants (actual)
Sponsor and investigators
- Lead sponsor
- Newron Pharmaceuticals SPA
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel, CliniRx
- Responsible party
- Sponsor
- Investigators
- Stefano Rossetti, MD, Study director, Newron Pharmaceuticals SPA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01019824
- Sponsor's protocol ID
- NW-1029/01-08
- Other IDs
- EudraCT Nr.: 2008-006176-30
- Status last verified
- Sep 2017
- First submitted
- 23 Nov 2009
- Last updated
- 15 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Study to Assess the Efficacy and Safety of Ralfinamide.
- ClinicalTrials.gov ID
- NCT01019824
- Acronym / sponsor ID
- NW-1029/01-08
- Conditions
- Pain
- Keywords
- nerve compression, compression radiculopathy, post-traumatic/post-surgical lumbar radiculopathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 411 participants (actual)
- Lead sponsor
- Newron Pharmaceuticals SPAIndustry (pharma, biotech, devices)
- Collaborators
- Parexel, CliniRx
- Study start
- 20 Mar 2009 (actual)
- Primary completion
- 11 May 2010 (actual)
- Study completion
- 9 Aug 2011 (actual)
- First posted
- 25 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to determine if an experimental drug, ralfinamide, relieves your neuropathic low back pain, and if it demonstrates superiority to placebo, a "dummy" or sugar pill that contains no active medication. Ralfinamide, given as either 160 mg/day or 320 mg/day, taken in a divided dose twice-a-day, will be compared with placebo. If you are randomly (by chance) selected to receive placebo, you will receive this medication throughout the treatment period of the study. Data from this study will provide essential information for choosing the doses of ralfinamide to be used in the treatment of this type of pain and potentially other types of pain.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low Dose | Experimental | Drug: Ralfinamide160 mg dose |
| High Dose | Experimental | Drug: Ralfinamide320 mg dose |
| Placebo | Placebo comparator | Drug: RalfinamidePlacebo Comparator |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must meet all of the following inclusion criteria to be eligible for enrolment into the study:
- 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.
Key exclusion criteria (8 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RalfinamideRalfinamide Oral Tablets, 160 or 320 mg per day | Drug | High Dose, Low Dose, Placebo |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefano Rossetti, MD study director
Newron Pharmaceuticals SPA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ralfinamide in people with Pain, run by Newron Pharmaceuticals SPA at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2017.