Crossover Study of CNV1014802 in Subjects With Neuropathic Pain From Lumbosacral Radiculopathy

Study Overview
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Brief Summary
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The study is a randomized, double blind, cross-over study to evaluate the safety and efficacy of CNV1014802 in subjects with neuropathic pain from lumbosacral radiculopathy.

Detailed Description
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The study consists of two treatment periods of 22 days with randomized CNV1014802 350mg or placebo administered twice daily. In addition, single blind placebo will be administered during a two week run-in, a two week wash-out period between the two treatment periods, and a one week run-out phase. This study was previously posted by Convergence Pharmaceuticals, Ltd., which has been acquired by Biogen.

Official Title
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A Randomized, Double Blind, Cross-over Study to Evaluate the Safety and Efficacy of CNV1014802 in Subjects With Neuropathic Pain From Lumbosacral Radiculopathy

Conditions
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Lumbosacral Radiculopathy

Intervention / Treatment
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* Drug: CNV1014802
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female aged between 18 and 65 years, with a diagnosis of neuropathic pain due to lumbosacral radiculopathy (LSR). Female subjects must be of non-child bearing potential or agree to use an approved form of contraception Body weight < 50 kg for men and < 45 kg for women. Capable of giving written informed consent. Approved concomitant medications must have been stable for at least 4 weeks prior to day 1. Average baseline daily pain score for neuropathic pain due to LSR on the 11-point numerical rating scale of 4 or greater. Key Exclusion Criteria: Subjects who are unable to reliably delineate or assess their own pain by anatomical location/distribution. Subjects with lumbar canal stenosis in which the pain in the lower limbs occur solely on walking and not at rest. Subjects with causes for their neuropathic pain other than LSR. Subjects who have received nerve blocks and/or steroid injections for neuropathic pain within 4 weeks prior to day 1. Subjects who are indicated for surgical treatment of lumbosacral radiculopathy. A positive pre-study drug screen. A positive history of HIV. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. History of any liver disease within the last 6 months, with the exception of known Gilbert's disease. History of excessive regular alcohol consumption within 6 months of the study. Subjects with a history or risk of seizures or a history of epilepsy, head injury or related neurological disorders Subjects with a history of uncontrolled or poorly controlled hypertension, with systolic BP frequently exceeding 160mmHg and/or diastolic BP frequently exceeding 100mmHg, or subjects who have BP greater than or equal to 160mmHg systolic and/or greater than or equal to 100mmHg diastolic at screening after repeated measurements History or presence of significant cardiovascular, gastro-intestinal, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs. Subjects with conditions known to affect cardiac conduction or a personal or familial history of Brugada syndrome Pregnant females or lactating females. History or presence of any clinically significant abnormality in vital signs / ECG / laboratory tests or have any medical or psychiatric condition, which, in the opinion of the Investigator may interfere with the study procedures or compromise subject safety. History of suicidal ideation and/or suicide attempts or clinical evidence of recent major depression. Subjects who are unable to maintain their same medications for the treatment of neuropathic pain at a stable dose during the study. Unable to refrain from excessive use of sedatives. Unable to comply with the prohibited concomitant medication restrictions as detailed in the protocol. This includes but is not limited to sodium channel blockers or drugs that adversely interact with a monoamine oxidase-B inhibitor: MAOI's, antidepressants, opioids and sympathomimetic agents. Unable to stop and remain abstained from non-pharmacological treatments for their neuropathic pain during the study. History of hypersensitivity to CNV1014802. The subject has participated in a clinical trial and has received an investigational product within 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) prior to the start of this study. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. Subject is mentally or legally incapacitated. NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CNV1014802<br>CNV1014802 350mg on prescription (BID) for 21 days | Drug: CNV1014802<br>* Administered as specified in treatment arm.<br>|
| Placebo Comparator: Placebo<br>Placebo 350mg BID for 21 days | Drug: Placebo<br>* Administered as specified in treatment arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Average Daily Neuropathic Pain Score from Baseline | Change in average daily neuropathic pain score from baseline (average days 10-14) to week 3 based on the 11 point Pain Intensity Numerical Rating Scale (PI-NRS) (0=no pain, 10=maximum pain imaginable). Subjects should specifically rate the pain intensity for the neuropathic pain associated with lumbosacral radiculopathy and not pain from other concomitant causes | Three weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical Pain Rating Scale | Change in average daily pain score from baseline (average days 10-14) to week 1 and week 2 of treatment and 1 week following the end of randomized treatment. | 3 weeks | 
| Responder Rate | Proportion of patients who have >= 30% and >=50% reduction in average daily pain score relative to baseline during weeks 1, 2 and 3 of treatment and 1 week following the end of randomized treatment. | 3 weeks | 
| Galer Neuropathic Pain Scale | Change in Galer Neuropathic Pain Scale from baseline to week 3 of treatment. | 3 weeks | 
| Oswestry Disability Index | Change in average disability score from baseline to week 1, week 2 and week 3 of treatment based on Oswestry Disability Index | 3 weeks | 
| PGIC | Proportion of patients who have improved, much improved or very much improved relative to baseline on the Patient Global Impression of Change (PGIC) on week 3 of treatment. | 3 weeks | 
| CGIC | Proportion of patients who have improved, much improved or very much improved relative to baseline on the Clinical Global Impression of Change (CGIC) on week 3 of treatment. | 3 weeks |