Lamotrigine Extended-Release In Elderly Patients With Epilepsy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00516139
First received: August 13, 2007
Last updated: August 16, 2012
Last verified: August 2012
  Purpose

This study is being conducted to determine the safety and tolerability of lamotrigine (LTG) in elderly patients with epilepsy. This study will be carried out using an extended-release formulation of lamotrigine (LTG-XR) that will allow once-a-day dosing.


Condition Intervention Phase
Epilepsy
Drug: Lamotrigine
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Lamotrigine Extended-Release in Elderly Patients With Epilepsy

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event [ Time Frame: From Baseline (Week 0) until 3 weeks after the end of treatment (Week 30 or 33) ] [ Designated as safety issue: Yes ]
    An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or causes its prolongation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. A complete list of all SAEs and AEs experienced in the study can be found in the SAE/AE section.


Secondary Outcome Measures:
  • Percent Change From Baseline (BL) in Weekly Seizure (sz.) Frequency for All Partial Seizures During Each Phase of the Study [ Time Frame: Baseline (Week 0), Dose-Escalation Phase (Week 7), Maintenance Phase (Week 15), Adjunctive Optimization Phase (Week 28), Conversion Phase (Week 20), Monotherapy Phase (Week 28), and end of treatment (Week 30 or 33) ] [ Designated as safety issue: No ]
    Partial-onset sz. have a focal site of onset; sz. activity is initially limited to 1 brain hemisphere. Partial sz. can remain simple or complex, or evolve to generalized tonic-clonic sz. Participants (par.) recorded the number of sz., by type as well as the episode duration of innumerable sz. activity), in daily diaries. If par. withdrew from study, data were averaged for the study portion the par. completed up to the time of drug discontinuation. Percent change from BL = (BL value minus study phase value divided by BL value) x 100; positive values indicate reduction from BL in sz. frequency.

  • Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study [ Time Frame: Baseline (Week 0), Dose-Escalation Phase (Week 7), Maintenance Phase (Week 15), Adjunctive Optimization (Adj O) Phase (Week 28), Conversion Phase (Week 20), Monotherapy Phase (Week 28), and end of treatment (ET, Week 30 or 33) ] [ Designated as safety issue: No ]
    Participants recorded the number of seizures, by seizure type, as well as the duration of episodes of innumerable seizure activity in their daily diaries during all phases of the study. For participants who withdrew from the study, seizure data were averaged for the portion of the study the participant completed up to the time of study drug discontinuation. Participants who experienced a change from Baseline in the weekly seizure frequency were categorized as having a >=25%, >=50%, >=75%, or 100% reduction or a >=50% increase in percent change from Baseline in weekly seizure frequency.

  • Number of Seizure-free Participants at Baseline Who Remained Seizure-free Throughout the Entire Treatment Period [ Time Frame: Week 30 or 33 ] [ Designated as safety issue: No ]
    Participants were considered to be seizure-free if they did not report any seizures at Baseline.

  • Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale [ Time Frame: Week 15 (Adjunctive Maintenance [Adj M] Phase), Week 28 (Adjunctive Optimization [Adj O] Phase), Week 28 (Monotherapy [Mono] Phase), and Week 28 (Early Withdrawal [WD]) ] [ Designated as safety issue: No ]
    Investigators rated the participants' seizure severity at Weeks 15 and 28 of the study treatment by using the IGE scale, comprised of 7 categories: 3 for improvement (mild improvement, moderate improvement, and marked improvement), 3 for deterioration (marked deterioration, moderate deterioration, mild deterioration), and 1 for no change. Investigators assessed the degree of the participants' improvement or deterioration or determined whether the participants' condition had not changed compared to their Baseline condition.

  • Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale [ Time Frame: Week 15 (Adjunctive Maintenance [Adj M] Phase), Week 28 (Adjunctive Optimization [Adj O] Phase), Week 28 (Monotherapy [Mono] Phase), and Week 28 (Early Withdrawal [WD]) ] [ Designated as safety issue: No ]
    Investigators rated the participants' overall clinical status at Weeks 15 and 28 of the study treatment by using the IGE scale, comprised of 7 categories: 3 for improvement (mild improvement, moderate improvement, and marked improvement), 3 for deterioration (marked deterioration, moderate deterioration, mild deterioration), and 1 for no change. Investigators assessed the degree of the participants' improvement or deterioration or determined whether the participants' condition had not changed compared to their Baseline condition.

  • Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points in the Study [ Time Frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), Week 28 (WD), and Week 30/33 (End of study [EOS]) ] [ Designated as safety issue: No ]
    Change from Baseline was calculated by subtracting the values of systolic and diastolic blood pressures recorded by the investigator at the indicated time points in the study from the respective Baseline values.

  • Change From Baseline in the Height at the Indicated Time Points in the Study [ Time Frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), Week 28 (WD), and Week 30/33 (End of study [EOS]) ] [ Designated as safety issue: No ]
    Change from Baseline was calculated by subtracting the value of height measured by the investigator at the indicated time points in the study from the Baseline value.

  • Change From Baseline in the Weight at the Indicated Time Points in the Study [ Time Frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), Week 28 (WD), and Week 30/33 (End of study [EOS]) ] [ Designated as safety issue: No ]
    Change from Baseline was calculated by subtracting the value of weight measured by the investigator at the indicated time points in the study from the Baseline value.

  • Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study [ Time Frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD) ] [ Designated as safety issue: No ]
    The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of basophil, eosinophil, hemoglobin, lymphocyte, monocyte, ANC, platelet count, and WBC count at the indicated time points in the study from the Baseline value.

  • Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study [ Time Frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD) ] [ Designated as safety issue: No ]
    The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Percent change from Baseline = (value at each indicated time point in the study minus respective Baseline value divided by Baseline value) x 100.

  • Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study [ Time Frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD) ] [ Designated as safety issue: No ]
    The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the values of MCHC, albumin, and total protein at the indicated time points in the study from the respective Baseline values.

  • Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points in the Study [ Time Frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD) ] [ Designated as safety issue: No ]
    The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of MCH at the indicated time points in the study from the Baseline value.

  • Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points in the the Study [ Time Frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD) ] [ Designated as safety issue: No ]
    The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of MCV at the indicated time points in the study from the Baseline value.

  • Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points in the Study [ Time Frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD) ] [ Designated as safety issue: No ]
    The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of RBC count at the indicated time points in the study from the Baseline value. Change from baseline is measured as the number of red blood cells x 10^12 per liter.

  • Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study [ Time Frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD) ] [ Designated as safety issue: No ]
    The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of Alk P, Ala AT, and Asp AT at the indicated time points in the study from the Baseline value.

  • Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study [ Time Frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD) ] [ Designated as safety issue: No ]
    The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of DB, TB, and creatinine at the indicated time points in the study from the Baseline value.

  • Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points [ Time Frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD) ] [ Designated as safety issue: No ]
    The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of cholesterol, HDL cholesterol, LDL cholesterol, glucose, potassium, sodium, triglycerides, and urea/BUN at the indicated time points in the study from the Baseline value.

  • Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA [ Time Frame: Weeks 4, 7, 11, 15, 20, 24, and 28 ] [ Designated as safety issue: No ]
    The blood samples were collected at the specified study visits; however, serum LTG concentrations were summarized by dose regimen, not by study week. The serum was assayed for LTG using an approved method under the management of Worldwide Bioanalysis, GlaxoSmithKline.

  • Apparent Clearance (CL/F) Based on the Concomitant AED Groups: Neutral, With EIAED, and With VPA [ Time Frame: Weeks 4, 7, 11, 15, 20, 24, and 28 ] [ Designated as safety issue: No ]
    Individual serum LTG concentration data were subjected to population pharmacokinetic methodologies based on the concomitant AED groups. Clearance is defined as the volume of LTG per unit time eliminated from serum. Serum LTG concentration-time data files incorporating, where appropriate, records of LTG administration, participant demography, and concomitant medication were supplied to Clinical Pharmacokinetics Modelling and Simulation, Clinical Pharmacology, and Discovery Medicine (CPDM) by Clinical Data Management as NONMEM compatible .csv files.

  • Apparent Volume of Distribution (V/F) for Participants in All Concomitant AED Groups Combined: Neutral, With EIAED, and With VPA [ Time Frame: Weeks 4, 7, 11, 15, 20, 24, and 28 ] [ Designated as safety issue: No ]
    Individual serum LTG concentration data were subjected to population pharmacokinetic methodologies based on the concomitant AED groups. V/F is defined as the apparent volume in which a drug is distributed immediately after it has been injected intravenously and equilibrated between plasma and the surrounding tissues. Serum LTG concentration-time data files incorporating, where appropriate, records of LTG administration, participant demography, and concomitant medication were supplied to CPDM by Clinical Data Management as NONMEM compatible .csv files.

  • Absorption Rate (KA) for Participants in All Concomitant AED Groups Combined: Neutral, With EIAED, and With VPA [ Time Frame: Weeks 4, 7, 11, 15, 20, 24, and 28 ] [ Designated as safety issue: No ]
    Individual serum LTG concentration data were subjected to population pharmacokinetic methodologies based on the concomitant AED groups. KA is defined as the rate at which a drug enters the body after administration. Serum LTG concentration-time data files incorporating, where appropriate, records of LTG administration, participant demography, and concomitant medication were supplied to CPDM by Clinical Data Management as NONMEM compatible .csv files.


Enrollment: 122
Study Start Date: August 2007
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lamotrigine
Open-label lamotrigine
Drug: Lamotrigine
Open-label
Other Name: Lamotrigine

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Confident diagnosis of epilepsy
  • Currently treated with one or two antiepileptic medications
  • Able to complete a seizure diary

Exclusion criteria:

  • History of hypersensitivity to lamotrigine
  • Progressive diseases that would interfere with the study objectives
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00516139

  Show 62 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00516139     History of Changes
Other Study ID Numbers: LEP105972
Study First Received: August 13, 2007
Results First Received: July 15, 2011
Last Updated: August 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Epilepsy elderly seizure

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Anticonvulsants
Lamotrigine
Calcium Channel Blockers
Cardiovascular Agents
Central Nervous System Agents
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sodium Channel Blockers
Therapeutic Uses
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on October 20, 2014