Trial to Assess Efficacy and Safety of Lacosamide in Subjects With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the effectiveness, safety and tolerability of lacosamide (LCM) 400mg/day in treating the signs and symptoms of osteoarthritis of the knee.

Detailed Description
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LCM is an investigational drug that is being studied as a treatment in male and female patients who are diagnosed with osteoarthritis of the knee and require therapeutic doses of NSAIDs, COX-2 NSAIDs and/or paracetamol. This trial will be conducted exclusively in Europe. The study has an adaptive 3-stage group sequential design. The trial will last a total of 17 weeks. There will be a 2 week period to wean off current medication, followed by a 4 week period where the patient will receive placebo (inactive drug) or gradually increasing doses of LCM up to the target dose of 400mg/day. The target dose or placebo will be maintained for 8 weeks followed by a 1 week reduction period then a 2 week safety follow up period. The last subject is expected to be enrolled in December 2007. The study was terminated based on the outcome of the planned first interim analysis, which was performed as defined in the protocol in a subset of patients. It was decided not to continue the trial. No safety concerns were identified.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of 400mg/Day Lacosamide in Subjects With Osteoarthritis of the Knee

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: lacosamide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has symptomatic osteoarthritis of the knee diagnosed using clinical and radiographic evidence as well as ACR criteria with symptom duration of at least 6 months. Subject requires therapeutic dose of an NSAID, COX-2 NSAID, and/or paracetamol/acetaminophen for osteoarthritis pain of the index knee and has taken that medication at least 5 days per week for the last 4 weeks prior to the screening visit (Visit 1). Exclusion Criteria: Subject is not able to withdraw NSAIDs, COX-2 NSAIDs and/or paracetamol Subject is taking analgesic other than NSAIDs COX-2 NSAIDs and/or paracetamol Subject is planning to begin or stop treatment with glucosamine and/or chondroitin during the trial

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lacosamide<br>lacosamide (LCM) | Drug: lacosamide<br>* 50 or 100mg tablet, 400mg daily, for 12 weeks<br>* Other names: VIMPAT;|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* 50 or 100mg tablet, 400mg daily, for 12 weeks, matched to Lacosamide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the Western Ontario and McMaster Universities (WOMAC) Pain Subscale Score (Visual Analogue Scale Version) From Baseline to the End of the 8 Week Maintenance Period | The Visual Analogue Scale (VAS) version of the WOMAC pain subscale ranges from 0 to 100, high values describe high grade of pain. | Baseline, end of 8 week Maintenance Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of 8 Week Maintenance Period in WOMAC Physical Function Subscale Score. | The WOMAC physical function subscale score (Visual Analogue Scale version) ranges from 0 to 100, high values describe high grade of difficulty in performing daily activities. | Baseline, end of 8 week Maintenance Period | 
| Change From Baseline to End of 8 Week Maintenance Period in WOMAC Stiffness Subscale Score. | The WOMAC stiffness subscale score (Visual Analogue Scale version) ranges from 0 to 100, high values describe high grade of stiffness. | Baseline, end of 8 week Maintenance Period | 
| Change From Baseline to End of 8 Week Maintenance Period in Total WOMAC Score. | The WOMAC total score is the sum of the normalized subscale scores for pain, stiffness, and physical function and ranges from 0 to 300, high values describe high grade of impact. | Baseline, end of 8 week Maintenance Period | 
| Patient's Global Impression of Change From Baseline at the End of 8 Week Maintenance Period. | Patient's global impression of change from baseline is a score that ranges from 'very much worse' to 'very much improved'. | at the end of 8 week Maintenance Period | 
| Response at the End of 8 Week Maintenance Period Versus Baseline Based on the (Slightly Modified)Criteria of the Osteoarthritis Research Society International (OARSI) and the Outcome Measures in Rheumatology Initiative (OMERACT). | Improvement = reduction of >= 20% and >= 10 mm in both WOMAC pain and physical function subscale. Those who met the criteria in either of the subscales had improved if response to Patient's Global Impression of change from baseline was at least 'mildly improved'. High improvement = reduction of >= 50% and >= 20 mm in either of the subscales. Response = either high improvement or improvement. | Baseline, end of 8 week Maintenance Period | 
| Amount of Rescue Medication Use During 8 Week Maintenance Period. | Use of rescue medication is expressed in number of tablets equivalent to 500 mg Paracetamol per day. | during 8 week Maintenance Period | 
| Change From Baseline to End of 8 Week Maintenance Period in Perception of Pain Interference With Subject's Sleep. | Pain interference with sleep refers to patient's last evening prior to the visit and was assessed using a 100mm visual analog scale (VAS). The VAS ranges from 0 (did not interfere) to 100 (completely interfered). | Baseline, end of 8 week Maintenance Period | 
| Change From Baseline to End of 8 Week Maintenance Period in Profile of Mood States (Total Mood Disturbance Score). | Total Mood Disturbance score sums up over the domain scores regarding Tension-anxiety, Depression-ejection, Anger-hostility, Vigor-activity (was subtracted), Fatigue-inertia, Confusion-bewilderment. Domain scores were derived as sum of the respective items and range from 0 to 20. With exception of Vigor-activity high values describe bad mood. | Baseline, end of 8 week Maintenance Period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, lacosamide, VIMPAT