Hormonal and Lipid Levels in Male Subjects After a Switch From Carbamazepine to Lacosamide (VICTOR)

• ClinicalTrials.gov Identifier: NCT01375374
• Recruitment Status: Terminated
• First Posted: June 17, 2011
• Results First Posted: November 26, 2014
• Last Update Posted: August 28, 2017
• Sponsor: UCB Pharma
• Information provided by (Responsible Party): UCB Pharma

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epilepsy, Partial
• Interventions: Drug: Lacosamide; Drug: Levetiracetam
• Enrollment: 11

Participant Flow

Recruitment Details	The study was conducted at 5 sites across Austria (1 site), Germany (3 sites), and Spain (1 site).
Pre-assignment Details	The study consisted of a 1-week Screening Period, a 12-week Treatment Period (comprised of a 4-week Titration Period and an 8-week Maintenance Period), and a Taper/Safety Follow-Up Period 3 to 4 weeks in duration.

Arm/Group Title	Lacosamide
Arm/Group Description	commercial 50 mg (pinkish) and 100 mg (yellow) tablets; Lacosamide: 4-week Titration Period: start dose Lacosamide (LCM) was 100 mg/day - up-titration of 100 mg/week LCM. 8-week Maintenance Period: dose could change first 4 weeks with 100 mg/week, needed to remain between 300 mg/day and 600 mg/day. Dose needed to remain stable last 4 weeks.; Levetiracetam: Levetiracetam (LEV) was taken at a stable dose 30 days before study entry and was ≥ 1000 mg/day at the first visit. The LEV dose could not be changed at any time.
Period Title: Overall Study
Started	11
Completed	10
Not Completed	1
Reason Not Completed
Adverse Event	1

Baseline Characteristics

Arm/Group Title		Lacosamide
Arm/Group Description		commercial 50 mg (pinkish) and 100 mg (yellow) tablets; Lacosamide: 4-week Titration Period: start dose Lacosamide (LCM) was 100 mg/day - up-titration of 100 mg/week LCM. 8-week Maintenance Period: dose could change first 4 weeks with 100 mg/week, needed to remain between 300 mg/day and 600 mg/day. Dose needed to remain stable last 4 weeks.; Levetiracetam: Levetiracetam (LEV) was taken at a stable dose 30 days before study entry and was ≥ 1000 mg/day at the first visit. The LEV dose could not be changed at any time.
Overall Number of Baseline Participants		11
Baseline Analysis Population Description		The Baseline Analysis Population refers to the Safety Set (SS). The SS consists of all patients who received at least 1 dose of Lacosamide.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	11 participants
		31.5 (5.9)
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	11 100.0%
	>=65 years	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants
	Female	0 0.0%
	Male	11 100.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	11 participants
American Indian or Alaska Native		1
Asian		0
Black or African American		0
Native Hawaiin or other Pacific Islander		0
White		9
Other/Mixed		1
Weight; Mean (Standard Deviation); Unit of measure: Kilograms
	Number Analyzed	11 participants
		82.81 (16.25)
Height; Mean (Standard Deviation); Unit of measure: Centimeters
	Number Analyzed	11 participants
		178.05 (10.14)
Body Mass Index; Mean (Standard Deviation); Unit of measure: Kilogram per square meter
	Number Analyzed	11 participants
		25.89 (3.01)

Outcome Measures

1. Primary Outcome

Title	Change in Serum Sex Hormone Binding Globulin (SHBG) From Baseline to Treatment Period End (Comprised of a 4-week Titration Period and an 8-week Maintenance Period)
Description	Due to premature termination of enrollment prior to achieving the planned sample size (a total of 28 subjects), this primary safety variable was assessed for descriptive purposes only. A negative value indicates an improvement.
Time Frame	From Day 1 (Baseline) to Day 84 (Treatment Period End)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Safety Set (SS). The SS consists of all subjects who received at least 1 dose of Lacosamide.

Arm/Group Title	Lacosamide
Arm/Group Description:	commercial 50 mg (pinkish) and 100 mg (yellow) tablets; Lacosamide: 4-week Titration Period: start dose Lacosamide (LCM) was 100 mg/day - up-titration of 100 mg/week LCM. 8-week Maintenance Period: dose could change first 4 weeks with 100 mg/week, needed to remain between 300 mg/day and 600 mg/day. Dose needed to remain stable last 4 weeks.; Levetiracetam: Levetiracetam (LEV) was taken at a stable dose 30 days before study entry and was ≥ 1000 mg/day at the first visit. The LEV dose could not be changed at any time.
Overall Number of Participants Analyzed	10
Median (Full Range); Unit of Measure: nmol/L
	-12.80; (-20.3 to 4.9)

2. Secondary Outcome

Title	Change in Sex Hormone Calculated Free Androgen Index Levels From Baseline to Treatment Period End (Comprised of a 4-week Titration Period and an 8-week Maintenance Period)
Description	The change in sex hormone calculated free androgen index (100 x Testosterone/sex hormone binding globulin) levels from Baseline to the end of Maintenance Period was summarized descriptively by visit. A negative value indicates an improvement.
Time Frame	From Day 1 (Baseline) to Day 84 (Treatment Period End)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Safety Set (SS). The SS consists of all subjects who received at least 1 dose of Lacosamide.

Arm/Group Title	Lacosamide
Arm/Group Description:	commercial 50 mg (pinkish) and 100 mg (yellow) tablets; Lacosamide: 4-week Titration Period: start dose Lacosamide (LCM) was 100 mg/day - up-titration of 100 mg/week LCM. 8-week Maintenance Period: dose could change first 4 weeks with 100 mg/week, needed to remain between 300 mg/day and 600 mg/day. Dose needed to remain stable last 4 weeks.; Levetiracetam: Levetiracetam (LEV) was taken at a stable dose 30 days before study entry and was ≥ 1000 mg/day at the first visit. The LEV dose could not be changed at any time.
Overall Number of Participants Analyzed	10
Median (Full Range); Unit of Measure: Free Androgen Index
	9.493; (2.39 to 26.46)

3. Secondary Outcome

Title	Change in Serum Thyroid Hormone Free Thyroxine Level From Baseline to Treatment Period End (Comprised of a 4-week Titration Period and an 8-week Maintenance Period)
Description	The change in the serum thyroid hormone free thyroxine level from Baseline to the end of the Maintenance Period was summarized descriptively by visit.
Time Frame	From Day 1 (Baseline) to Day 84 (Treatment Period End)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Safety Set (SS). The SS consists of all subjects who received at least 1 dose of Lacosamide.

Arm/Group Title	Lacosamide
Arm/Group Description:	commercial 50 mg (pinkish) and 100 mg (yellow) tablets; Lacosamide: 4-week Titration Period: start dose Lacosamide (LCM) was 100 mg/day - up-titration of 100 mg/week LCM. 8-week Maintenance Period: dose could change first 4 weeks with 100 mg/week, needed to remain between 300 mg/day and 600 mg/day. Dose needed to remain stable last 4 weeks.; Levetiracetam: Levetiracetam (LEV) was taken at a stable dose 30 days before study entry and was ≥ 1000 mg/day at the first visit. The LEV dose could not be changed at any time.
Overall Number of Participants Analyzed	10
Median (Full Range); Unit of Measure: pmol/L
	2.70; (1.5 to 5.5)

4. Secondary Outcome

Title	Change in Total Cholesterol Level From Baseline to Treatment Period End (Comprised of a 4-week Titration Period and an 8-week Maintenance Period)
Description	The change in total cholesterol levels from Baseline to the end of the Maintenance Period was summarized descriptively by visit. A negative value indicates an improvement.
Time Frame	From Day 1 (Baseline) to Day 84 (Treatment Period End)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Safety Set (SS). The SS consists of all subjects who received at least 1 dose of Lacosamide.

Arm/Group Title	Lacosamide
Arm/Group Description:	commercial 50 mg (pinkish) and 100 mg (yellow) tablets; Lacosamide: 4-week Titration Period: start dose Lacosamide (LCM) was 100 mg/day - up-titration of 100 mg/week LCM. 8-week Maintenance Period: dose could change first 4 weeks with 100 mg/week, needed to remain between 300 mg/day and 600 mg/day. Dose needed to remain stable last 4 weeks.; Levetiracetam: Levetiracetam (LEV) was taken at a stable dose 30 days before study entry and was ≥ 1000 mg/day at the first visit. The LEV dose could not be changed at any time.
Overall Number of Participants Analyzed	10
Median (Full Range); Unit of Measure: mmol/L
	-0.540; (-1.46 to 0.11)

Adverse Events

Time Frame	Treatment Emergent Adverse Event were reported from Baseline until the Safety Follow-up Visit (two weeks after end of Treatment Period).
Adverse Event Reporting Description	Only Treatment Emergent Adverse Events are presented.
Arm/Group Title	Lacosamide
Arm/Group Description	commercial 50 mg (pinkish) and 100 mg (yellow) tablets; Lacosamide: 4-week Titration Period: start dose Lacosamide (LCM) was 100 mg/day - up-titration of 100 mg/week LCM. 8-week Maintenance Period: dose could change first 4 weeks with 100 mg/week, needed to remain between 300 mg/day and 600 mg/day. Dose needed to remain stable last 4 weeks.; Levetiracetam: Levetiracetam (LEV) was taken at a stable dose 30 days before study entry and was ≥ 1000 mg/day at the first visit. The LEV dose could not be changed at any time.
All-Cause Mortality
	Lacosamide
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Lacosamide
	Affected / at Risk (%)	# Events
Total	0/11 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Lacosamide
	Affected / at Risk (%)	# Events
Total	5/11 (45.45%)
General disorders
Fatigue * 1	1/11 (9.09%)	1
Infections and infestations
Bronchitis * 1	1/11 (9.09%)	1
Influenza * 1	1/11 (9.09%)	1
Nervous system disorders
Convulsion * 1	1/11 (9.09%)	1
Disturbance in attention * 1	1/11 (9.09%)	1
Paraesthesia * 1	1/11 (9.09%)	1
Partial seizures * 1	1/11 (9.09%)	1
Tremor * 1	1/11 (9.09%)	1
Psychiatric disorders
Aggression * 1	1/11 (9.09%)	1
Vascular disorders
Hot flush * 1	1/11 (9.09%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 16.1

Limitations and Caveats

The results of this study are limited due to the small sample size.

More Information

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.

Results Point of Contact

• Name/Title: UCB Clinical Trial Call Center
• Organization: UCB
• Phone: +1 877 822 9493

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Elger CE, Rademacher M, Brandt C, Elmoufti S, Dedeken P, Eckhardt K, Tennigkeit F, De Backer M. Changes in hormone and lipid levels in male patients with focal seizures when switched from carbamazepine to lacosamide as adjunctive treatment to levetiracetam: A small phase IIIb, prospective, multicenter, open-label trial. Epilepsy Behav. 2016 Sep;62:1-5. doi: 10.1016/j.yebeh.2016.05.023. Epub 2016 Jul 15.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT01375374
• Other Study ID Numbers: SP0978; 2010-022534-84 ( EudraCT Number )
• First Submitted: May 9, 2011
• First Posted: June 17, 2011
• Results First Submitted: November 20, 2014
• Results First Posted: November 26, 2014
• Last Update Posted: August 28, 2017