Trial Outcomes & Findings for Trial to Assess Efficacy and Safety of Lacosamide in Subjects With Osteoarthritis of the Knee (NCT NCT00485472)

NCT ID: NCT00485472

Last Updated: 2017-08-28

Results Overview

The Visual Analogue Scale (VAS) version of the WOMAC pain subscale ranges from 0 to 100, high values describe high grade of pain.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 194 participants
• Primary outcome timeframe: Baseline, end of 8 week Maintenance Period
• Results posted on: 2017-08-28

Participant Flow

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).

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).

Participant milestones

Measure	Lacosamide Lacosamide (LCM) 400 mg/day	Placebo Placebo
Overall Study STARTED	73	76
Overall Study Entered Maintenance Phase	65	67
Overall Study COMPLETED	57	64
Overall Study NOT COMPLETED	16	12

Reasons for withdrawal

Measure	Lacosamide Lacosamide (LCM) 400 mg/day	Placebo Placebo
Overall Study Adverse Event	8	5
Overall Study Lack of Efficacy	5	4
Overall Study Withdrawal by Subject	1	0
Overall Study Protocol Violation	0	1
Overall Study Other	2	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Lacosamide n=73 Participants Lacosamide (LCM) 400 mg/day	Placebo n=76 Participants Placebo	Total n=149 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	40 Participants n=5 Participants	46 Participants n=7 Participants	86 Participants n=5 Participants
Age, Categorical >=65 years	33 Participants n=5 Participants	30 Participants n=7 Participants	63 Participants n=5 Participants
Age, Continuous	61.0 years STANDARD_DEVIATION 8.03 • n=5 Participants	62.3 years STANDARD_DEVIATION 6.74 • n=7 Participants	61.7 years STANDARD_DEVIATION 7.40 • n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	59 Participants n=7 Participants	111 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	17 Participants n=7 Participants	38 Participants n=5 Participants
Region of Enrollment Hungary	20 participants n=5 Participants	22 participants n=7 Participants	42 participants n=5 Participants
Region of Enrollment Czech Republic	8 participants n=5 Participants	10 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Germany	27 participants n=5 Participants	27 participants n=7 Participants	54 participants n=5 Participants
Region of Enrollment Poland	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Romania	9 participants n=5 Participants	8 participants n=7 Participants	17 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, end of 8 week Maintenance Period

Population: 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.

The Visual Analogue Scale (VAS) version of the WOMAC pain subscale ranges from 0 to 100, high values describe high grade of pain.

Outcome measures

Measure	Lacosamide n=71 Participants Lacosamide (LCM) 400 mg/day	Placebo n=74 Participants Placebo
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	-24.85 Unit on a scale Standard Deviation 23.75	-28.49 Unit on a scale Standard Deviation 22.27

SECONDARY outcome

Timeframe: Baseline, end of 8 week Maintenance Period

Population: 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.

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.

Outcome measures

Measure	Lacosamide n=71 Participants Lacosamide (LCM) 400 mg/day	Placebo n=74 Participants Placebo
Change From Baseline to End of 8 Week Maintenance Period in WOMAC Physical Function Subscale Score.	-17.09 Unit on a scale Standard Deviation 21.74	-23.31 Unit on a scale Standard Deviation 22.45

SECONDARY outcome

Timeframe: Baseline, end of 8 week Maintenance Period

Population: 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.

The WOMAC stiffness subscale score (Visual Analogue Scale version) ranges from 0 to 100, high values describe high grade of stiffness.

Outcome measures

Measure	Lacosamide n=71 Participants Lacosamide (LCM) 400 mg/day	Placebo n=74 Participants Placebo
Change From Baseline to End of 8 Week Maintenance Period in WOMAC Stiffness Subscale Score.	-18.92 Unit on a scale Standard Deviation 26.11	-23.43 Unit on a scale Standard Deviation 24.00

SECONDARY outcome

Timeframe: Baseline, end of 8 week Maintenance Period

Population: 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.

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.

Outcome measures

Measure	Lacosamide n=71 Participants Lacosamide (LCM) 400 mg/day	Placebo n=74 Participants Placebo
Change From Baseline to End of 8 Week Maintenance Period in Total WOMAC Score.	-60.85 Unit on a scale Standard Deviation 66.85	-75.24 Unit on a scale Standard Deviation 65.61

SECONDARY outcome

Timeframe: at the end of 8 week Maintenance Period

Population: 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.

Patient's global impression of change from baseline is a score that ranges from 'very much worse' to 'very much improved'.

Outcome measures

Measure	Lacosamide n=68 Participants Lacosamide (LCM) 400 mg/day	Placebo n=72 Participants Placebo
Patient's Global Impression of Change From Baseline at the End of 8 Week Maintenance Period. Very much worse	4 Participants	1 Participants
Patient's Global Impression of Change From Baseline at the End of 8 Week Maintenance Period. Much worse	1 Participants	5 Participants
Patient's Global Impression of Change From Baseline at the End of 8 Week Maintenance Period. Worse	10 Participants	10 Participants
Patient's Global Impression of Change From Baseline at the End of 8 Week Maintenance Period. No change	18 Participants	10 Participants
Patient's Global Impression of Change From Baseline at the End of 8 Week Maintenance Period. Mildly improved	12 Participants	30 Participants
Patient's Global Impression of Change From Baseline at the End of 8 Week Maintenance Period. Much improved	15 Participants	13 Participants
Patient's Global Impression of Change From Baseline at the End of 8 Week Maintenance Period. Very much improved	8 Participants	3 Participants
Patient's Global Impression of Change From Baseline at the End of 8 Week Maintenance Period. Much + very much improved	23 Participants	16 Participants
Patient's Global Impression of Change From Baseline at the End of 8 Week Maintenance Period. Much + very much + mildly improved	35 Participants	46 Participants

SECONDARY outcome

Timeframe: Baseline, end of 8 week Maintenance Period

Population: 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.

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.

Outcome measures

Measure	Lacosamide n=71 Participants Lacosamide (LCM) 400 mg/day	Placebo n=74 Participants Placebo
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). High improvement	33 participants	32 participants
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	38 participants	52 participants
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). Response	38 participants	52 participants

SECONDARY outcome

Timeframe: during 8 week Maintenance Period

Population: 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.

Use of rescue medication is expressed in number of tablets equivalent to 500 mg Paracetamol per day.

Outcome measures

Measure	Lacosamide n=65 Participants Lacosamide (LCM) 400 mg/day	Placebo n=67 Participants Placebo
Amount of Rescue Medication Use During 8 Week Maintenance Period.	0.48 tablets/day Standard Deviation 0.62	0.70 tablets/day Standard Deviation 0.79

SECONDARY outcome

Timeframe: Baseline, end of 8 week Maintenance Period

Population: 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.

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).

Outcome measures

Measure	Lacosamide n=57 Participants Lacosamide (LCM) 400 mg/day	Placebo n=64 Participants Placebo
Change From Baseline to End of 8 Week Maintenance Period in Perception of Pain Interference With Subject's Sleep.	-19.8 Unit on a scale Standard Deviation 26.55	-21.6 Unit on a scale Standard Deviation 26.76

SECONDARY outcome

Timeframe: Baseline, end of 8 week Maintenance Period

Population: 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.

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.

Outcome measures

Measure	Lacosamide n=69 Participants Lacosamide (LCM) 400 mg/day	Placebo n=73 Participants Placebo
Change From Baseline to End of 8 Week Maintenance Period in Profile of Mood States (Total Mood Disturbance Score).	0.9 Unit on a scale Standard Deviation 17.99	-4.5 Unit on a scale Standard Deviation 14.25

Adverse Events

Lacosamide

Serious events: 4 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lacosamide n=72 participants at risk Lacosamide (LCM) 400 mg/day	Placebo n=76 participants at risk Placebo
Cardiac disorders Angina pectoris	1.4% 1/72	0.00% 0/76
Cardiac disorders Sick sinus syndrome	1.4% 1/72	0.00% 0/76
Hepatobiliary disorders Liver disorder	1.4% 1/72	0.00% 0/76
Metabolism and nutrition disorders Shock hypoglycaemic	1.4% 1/72	0.00% 0/76
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/72	1.3% 1/76
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer in situ	1.4% 1/72	0.00% 0/76
Vascular disorders Thrombophlebitis	0.00% 0/72	1.3% 1/76

Other adverse events

Measure	Lacosamide n=72 participants at risk Lacosamide (LCM) 400 mg/day	Placebo n=76 participants at risk Placebo
Ear and labyrinth disorders Vertigo	11.1% 8/72	1.3% 1/76
General disorders Fatigue	5.6% 4/72	2.6% 2/76
Infections and infestations Nasopharyngitis	4.2% 3/72	5.3% 4/76
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 4/72	5.3% 4/76
Nervous system disorders Headache	4.2% 3/72	5.3% 4/76

Additional Information

UCB Clinical Trial Call Center

UCB Pharma

Phone: +1 877 822 9493

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER