A multi-center, open-label, single-arm study to evaluate hormone and lipid levels in male subjects with partial onset seizures after a switch of treatment from carbamazepine as adjunctive treatment to levetiracetam to lacosamide as adjunctive treatment to levetiracetam.

• Conditions: Epilepsy: partial onset seizures.; MedDRA version: 14.1Level: PTClassification code 10015037Term: EpilepsySystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2010-022534-84-AT
• Lead Sponsor: CB Pharma SA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-10-20
• Last Update Posted: 27 January 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 28

Inclusion Criteria

1.An Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the subject or legal representative.
2.Subject/legal representative is considered reliable and capable of adhering to the protocol, visit schedule or medication intake according to the judgment of the investigator.
3.Subject is male and between 18 and 45 years of age, inclusive.
4.Subject has a diagnosis of epilepsy with partial-onset seizures according to the International Classification of Epileptic Seizures (1981) (See Section 15.1).
5.Subject is only taking LEV in combination with CBZ as adjunctive treatment for epilepsy.
6.Subject has been treated with CBZ for at least 12 months before study entry.
7.Subject has been maintained on a stable dose of CBZ and LEV during the 30 days before study entry.
8.The dose of CBZ at Visit 1 is =600mg/day to =1200mg/day.
9.The dose of LEV at Visit 1 is =1000mg/day.
10. Subjects for whom a change from adjunctive treatment of CBZ and LEV to adjunctive
treatment of LCM and LEV are expected to benefit according to the clinical judgment of
the investigator. These benefits are related to:
• Seizure control and/or
• Tolerability of the treatment and/or
• Endocrine/metabolic function and/or
• Drug-drug interactions
Are the trial subjects under 18? no
Number of subjects for this age range: 28
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 28
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects are not permitted to enroll in the study if any of the following criteria are met:
1.Subject has previously participated in this study or subject has previously been assigned to treatment in a study of LCM.
2.Subject has participated in another study of an investigational medicinal product (IMP) or an experimental medical device within the last 30 days or is currently participating in another study of an IMP or a medical device.
3.Subject has a known hypersensitivity to any components of LCM tablets.
4.Subject has taken an AED other than CBZ and LEV within the last 30 days, excepting 1 time use of benzodiazepines as rescue medication (less than or equal to 3 doses within 24 hours).
5. Subject has taken lipid lowering agents within the last 30 days.
6. Subject has taken any medication known to affect endocrine function within the last 30 days, including exogenous hormones (eg, thyroid hormone, anabolic steroids, androgens, or glucocorticoids).
7.Subject has taken other enzyme inducers within the last 30 days (eg, St. John’s wort, rifampicin).
8.Subject is suffering from a known endocrine disorder where the condition or its treatment might influence SHBG levels, reproductive hormones, thyroid hormones, or serum lipid levels.
9.Subject has a medical condition that could reasonably be expected to interfere with drug absorption, distribution, metabolism, or excretion.
10.Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject’s ability to participate in this study.
11.Deleted and no longer applicable beginning with Protocol Amendment 2 (see protocol amendment details in Section 15.3).
12.Subject has an acute or sub-acute progressive central nervous system disease.
13.Subject has a history of chronic alcohol or drug abuse within the last 2 years.
14.Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias.
15.Subject has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels =2x the upper limit of normal (ULN) or has alkaline phosphatase levels =3x ULN at Visit 1.
16.Subject has impaired renal function (ie, creatinine clearance [CLcr] is lower than 30mL/min) at Baseline. Creatinine clearance will be estimated as follows:
Adult males: CLcr = (140-age) x weight in kg/(72 x serum creatinine in mg/dL)
17.Subject has a sick sinus syndrome without a pacemaker, or second or third degree atrioventricular (AV) block.
18.Subject has a known sodium channelopathy, such as Brugada syndrome.
19.Subject has experienced a myocardial infarction in the last 3 months.
20.Subject has New York Heart Association Class III or Class IV heart failure.
21.Subject with concomitant treatment of felbamate or previous felbamate therapy within the last 6 months prior to study entry.
22.Subject with previous or concomitant vigabatrin use.
23.Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response Yes” to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of this study is to evaluate the change in hormonal parameters and lipid parameters in serum after switching from Carbamazepine treatment to Lacosamide treatment as adjunctive therapy to Levetiracetam.;Secondary Objective: See section 4.1 of the protocol.;Primary end point(s): Change in serum SHBG concentration from Baseline to the end of the Maintenance Period<br><br>;Timepoint(s) of evaluation of this end point: End of maintenance period (12 weeks after start of treatment)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Change in the sex hormone calculated free androgen index (=100x testosterone/SHBG) levels from Baseline to the end of the Maintenance Period<br><br>Change in the serum thyroid hormone fT4 level from Baseline to the end of the end of the Maintenance Period<br><br>Change in total cholesterol levels from Baseline to the end of the Maintenance Period<br><br>;Timepoint(s) of evaluation of this end point: End of maintenance period (12 weeks after start of treatment)