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

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

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.

Study Overview

• Status: Completed
• Conditions: Lumbosacral Radiculopathy
• Intervention / Treatment: Drug: CNV1014802; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia
    • Research Site
  • Litomerice, Czechia
    • Research Site
  • Prachatice, Czechia
    • Research Site
• Denmark
  • Glostrup, Denmark
    • Research Site
  • Odense, Denmark
    • Research Site
• France
  • Lille, France
    • Research Site
  • Nice, France
    • Research Site
  • Paris, France
    • Research Site
  • Saint-Etienne, France
    • Research Site
• Sweden
  • Gothenburg, Sweden
    • Research Site
  • Malmo, Sweden
    • Research Site
  • Stockholm, Sweden
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2011
• Primary Completion (Actual): June 30, 2012
• Study Completion (Actual): August 31, 2012

Study Registration Dates

• First Submitted: March 19, 2012
• First Submitted That Met QC Criteria: March 21, 2012
• First Posted (Estimate): March 22, 2012

Study Record Updates

• Last Update Posted (Actual): October 13, 2017
• Last Update Submitted That Met QC Criteria: October 12, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Radiculopathy
• Other Study ID Numbers: CNV1014802/201