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Trial record 1 of 1 for:    NCT00485472
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Trial to Assess Efficacy and Safety of Lacosamide in Subjects With Osteoarthritis of the Knee

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ClinicalTrials.gov Identifier: NCT00485472
Recruitment Status : Terminated (Based on the outcome of the planned first interim analysis, it was decided not to continue the trial. No safety concerns were identified.)
First Posted : June 13, 2007
Results First Posted : September 22, 2009
Last Update Posted : August 28, 2017
Sponsor:
Information provided by (Responsible Party):
UCB Pharma

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Osteoarthritis
Interventions Drug: lacosamide
Other: Placebo
Enrollment 194
Recruitment Details Trial utilized an adaptive 3-stage group sequential design. The Data Monitoring Committee had recommended to stop the trial after the first stage due to lack of efficacy. Results refer to the entire population randomized until discontinuation of study (including overrun).
Pre-assignment Details Of the 194 enrolled subjects, 149 subjects have been randomized until trial termination. The Participants flow refers to the randomized population. Of the 149 randomized subjects, 148 subjects have been treated and are included in the safety population, 145 have been included in the ITT population (Full Analysis Set).
Arm/Group Title Lacosamide Placebo
Hide Arm/Group Description Lacosamide (LCM) 400 mg/day Placebo
Period Title: Overall Study
Started 73 76
Entered Maintenance Phase 65 67
Completed 57 64
Not Completed 16 12
Reason Not Completed
Adverse Event             8             5
Lack of Efficacy             5             4
Withdrawal by Subject             1             0
Protocol Violation             0             1
Other             2             1
Lost to Follow-up             0             1
Arm/Group Title Lacosamide Placebo Total
Hide Arm/Group Description Lacosamide (LCM) 400 mg/day Placebo Total of all reporting groups
Overall Number of Baseline Participants 73 76 149
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 73 participants 76 participants 149 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
40
  54.8%
46
  60.5%
86
  57.7%
>=65 years
33
  45.2%
30
  39.5%
63
  42.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 73 participants 76 participants 149 participants
61.0  (8.03) 62.3  (6.74) 61.7  (7.40)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 73 participants 76 participants 149 participants
Female
52
  71.2%
59
  77.6%
111
  74.5%
Male
21
  28.8%
17
  22.4%
38
  25.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 73 participants 76 participants 149 participants
Hungary 20 22 42
Czech Republic 8 10 18
Germany 27 27 54
Poland 9 9 18
Romania 9 8 17
1.Primary Outcome
Title 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
Hide Description The Visual Analogue Scale (VAS) version of the WOMAC pain subscale ranges from 0 to 100, high values describe high grade of pain.
Time Frame Baseline, end of 8 week Maintenance Period
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), defined as all randomized subjects that have received at least one dose of trial medication and had at least one post-baseline WOMAC assessment. Last observation carried forward (LOCF) imputation method was applied in case of missing WOMAC assessment.
Arm/Group Title Lacosamide Placebo
Hide Arm/Group Description:
Lacosamide (LCM) 400 mg/day
Placebo
Overall Number of Participants Analyzed 71 74
Mean (Standard Deviation)
Unit of Measure: Unit on a scale
-24.85  (23.75) -28.49  (22.27)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lacosamide, Placebo
Comments The ANCOVA analysis includes treatment and pooled site as factors and baseline score as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5438
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.36
Confidence Interval 95%
-5.30 to 10.02
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to End of 8 Week Maintenance Period in WOMAC Physical Function Subscale Score.
Hide Description 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.
Time Frame Baseline, end of 8 week Maintenance Period
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), defined as all randomized subjects that have received at least one dose of trial medication and had at least one post-baseline WOMAC assessment. LOCF imputation method was applied in case of missing WOMAC assessment.
Arm/Group Title Lacosamide Placebo
Hide Arm/Group Description:
Lacosamide (LCM) 400 mg/day
Placebo
Overall Number of Participants Analyzed 71 74
Mean (Standard Deviation)
Unit of Measure: Unit on a scale
-17.09  (21.74) -23.31  (22.45)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lacosamide, Placebo
Comments The ANCOVA analysis includes treatment and pooled site as factors and baseline score as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2022
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.83
Confidence Interval 95%
-2.62 to 12.28
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to End of 8 Week Maintenance Period in WOMAC Stiffness Subscale Score.
Hide Description The WOMAC stiffness subscale score (Visual Analogue Scale version) ranges from 0 to 100, high values describe high grade of stiffness.
Time Frame Baseline, end of 8 week Maintenance Period
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), defined as all randomized subjects that have received at least one dose of trial medication and had at least one post-baseline WOMAC assessment. LOCF imputation method was applied in case of missing WOMAC assessment.
Arm/Group Title Lacosamide Placebo
Hide Arm/Group Description:
Lacosamide (LCM) 400 mg/day
Placebo
Overall Number of Participants Analyzed 71 74
Mean (Standard Deviation)
Unit of Measure: Unit on a scale
-18.92  (26.11) -23.43  (24.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lacosamide, Placebo
Comments The ANCOVA analysis includes treatment and pooled site as factors and baseline score as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6650
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.79
Confidence Interval 95%
-6.36 to 9.93
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to End of 8 Week Maintenance Period in Total WOMAC Score.
Hide Description 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.
Time Frame Baseline, end of 8 week Maintenance Period
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), defined as all randomized subjects that have received at least one dose of trial medication and had at least one post-baseline WOMAC assessment. LOCF imputation method was applied in case of missing WOMAC assessment.
Arm/Group Title Lacosamide Placebo
Hide Arm/Group Description:
Lacosamide (LCM) 400 mg/day
Placebo
Overall Number of Participants Analyzed 71 74
Mean (Standard Deviation)
Unit of Measure: Unit on a scale
-60.85  (66.85) -75.24  (65.61)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lacosamide, Placebo
Comments The ANCOVA analysis includes treatment and pooled site as factors and baseline score as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3445
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 10.74
Confidence Interval 95%
-11.65 to 33.13
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Patient's Global Impression of Change From Baseline at the End of 8 Week Maintenance Period.
Hide Description Patient's global impression of change from baseline is a score that ranges from 'very much worse' to 'very much improved'.
Time Frame at the end of 8 week Maintenance Period
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), defined as all randomized subjects that have received at least one dose of trial medication and had at least one post-baseline WOMAC assessment. Only subjects with non-missing measurements of Patient's global impression of change from baseline were included.
Arm/Group Title Lacosamide Placebo
Hide Arm/Group Description:
Lacosamide (LCM) 400 mg/day
Placebo
Overall Number of Participants Analyzed 68 72
Measure Type: Number
Unit of Measure: Participants
Very much worse 4 1
Much worse 1 5
Worse 10 10
No change 18 10
Mildly improved 12 30
Much improved 15 13
Very much improved 8 3
Much + very much improved 23 16
Much + very much + mildly improved 35 46
6.Secondary Outcome
Title 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).
Hide Description 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.
Time Frame Baseline, end of 8 week Maintenance Period
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), defined as all randomized subjects that have received at least one dose of trial medication and had at least one post-baseline WOMAC assessment. Dropouts due to lack of efficay were defined as non-responders. For dropouts due to any other reason LOCF was applied to the underlying WOMAC subscale scores.
Arm/Group Title Lacosamide Placebo
Hide Arm/Group Description:
Lacosamide (LCM) 400 mg/day
Placebo
Overall Number of Participants Analyzed 71 74
Measure Type: Number
Unit of Measure: participants
High improvement 33 32
Improvement 38 52
Response 38 52
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lacosamide, Placebo
Comments Analysis of 'response' based on a likelihood ratio test with treatment and pooled site as factors.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0418
Comments [Not Specified]
Method Likelihood ratio test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.488
Confidence Interval 95%
0.245 to 0.974
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Amount of Rescue Medication Use During 8 Week Maintenance Period.
Hide Description Use of rescue medication is expressed in number of tablets equivalent to 500 mg Paracetamol per day.
Time Frame during 8 week Maintenance Period
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), defined as all randomized subjects that have received at least one dose of trial medication and had at least one post-baseline WOMAC assessment. Only subjects who entered the Maintenance Phase were included.
Arm/Group Title Lacosamide Placebo
Hide Arm/Group Description:
Lacosamide (LCM) 400 mg/day
Placebo
Overall Number of Participants Analyzed 65 67
Mean (Standard Deviation)
Unit of Measure: tablets/day
0.48  (0.62) 0.70  (0.79)
8.Secondary Outcome
Title Change From Baseline to End of 8 Week Maintenance Period in Perception of Pain Interference With Subject's Sleep.
Hide Description 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).
Time Frame Baseline, end of 8 week Maintenance Period
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), defined as all randomized subjects that have received at least one dose of trial medication and had at least one post-baseline WOMAC assessment. Only subjects with non-missing values were included.
Arm/Group Title Lacosamide Placebo
Hide Arm/Group Description:
Lacosamide (LCM) 400 mg/day
Placebo
Overall Number of Participants Analyzed 57 64
Mean (Standard Deviation)
Unit of Measure: Unit on a scale
-19.8  (26.55) -21.6  (26.76)
9.Secondary Outcome
Title Change From Baseline to End of 8 Week Maintenance Period in Profile of Mood States (Total Mood Disturbance Score).
Hide Description 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.
Time Frame Baseline, end of 8 week Maintenance Period
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), defined as all randomized subjects that have received at least one dose of trial medication and had at least one post-baseline WOMAC assessment. Only subjects with non-missing values were included.
Arm/Group Title Lacosamide Placebo
Hide Arm/Group Description:
Lacosamide (LCM) 400 mg/day
Placebo
Overall Number of Participants Analyzed 69 73
Mean (Standard Deviation)
Unit of Measure: Unit on a scale
0.9  (17.99) -4.5  (14.25)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lacosamide Placebo
Hide Arm/Group Description Lacosamide (LCM) 400 mg/day Placebo
All-Cause Mortality
Lacosamide Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Lacosamide Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   4/72 (5.56%)   2/76 (2.63%) 
Cardiac disorders     
Angina pectoris * 1  1/72 (1.39%)  0/76 (0.00%) 
Sick sinus syndrome * 1  1/72 (1.39%)  0/76 (0.00%) 
Hepatobiliary disorders     
Liver disorder * 1  1/72 (1.39%)  0/76 (0.00%) 
Metabolism and nutrition disorders     
Shock hypoglycaemic * 1  1/72 (1.39%)  0/76 (0.00%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion * 1  0/72 (0.00%)  1/76 (1.32%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer in situ * 1  1/72 (1.39%)  0/76 (0.00%) 
Vascular disorders     
Thrombophlebitis * 1  0/72 (0.00%)  1/76 (1.32%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 10.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lacosamide Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   16/72 (22.22%)   13/76 (17.11%) 
Ear and labyrinth disorders     
Vertigo * 1  8/72 (11.11%)  1/76 (1.32%) 
General disorders     
Fatigue * 1  4/72 (5.56%)  2/76 (2.63%) 
Infections and infestations     
Nasopharyngitis * 1  3/72 (4.17%)  4/76 (5.26%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  4/72 (5.56%)  4/76 (5.26%) 
Nervous system disorders     
Headache * 1  3/72 (4.17%)  4/76 (5.26%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 10.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
UCB has > 60 days but <= 180 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: UCB Clinical Trial Call Center
Organization: UCB Pharma
Phone: +1 877 822 9493
Layout table for additonal information
Responsible Party: UCB Pharma
ClinicalTrials.gov Identifier: NCT00485472    
Other Study ID Numbers: SP0905
2006-005048-97 ( EudraCT Number )
First Submitted: June 12, 2007
First Posted: June 13, 2007
Results First Submitted: August 12, 2009
Results First Posted: September 22, 2009
Last Update Posted: August 28, 2017