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Lamotrigine Extended-Release In Elderly Patients With Epilepsy

Primary Purpose

Epilepsy

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Lamotrigine

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Epilepsy elderly seizure

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lamotrigine

Arm Description

Open-label lamotrigine

Outcomes

Primary Outcome Measures

Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

Full Information

NCT ID

NCT00516139

First Posted

August 13, 2007

Last Updated

November 30, 2016

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT00516139

Brief Title

Lamotrigine Extended-Release In Elderly Patients With Epilepsy

Official Title

Lamotrigine Extended-Release in Elderly Patients With Epilepsy

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Completed

Study Start Date

August 2007 (undefined)

Primary Completion Date

July 2010 (Actual)

Study Completion Date

July 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epilepsy

Keywords

Epilepsy elderly seizure

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

122 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lamotrigine

Arm Type

Experimental

Arm Description

Open-label lamotrigine

Intervention Type

Drug

Intervention Name(s)

Lamotrigine

Intervention Description

Open-label

Primary Outcome Measure Information:

Title

Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event

Description

Time Frame

From Baseline (Week 0) until 3 weeks after the end of treatment (Week 30 or 33)

Secondary Outcome Measure Information:

Title

Percent Change From Baseline (BL) in Weekly Seizure (sz.) Frequency for All Partial Seizures During Each Phase of the Study

Description

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)

Title

Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study

Description

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)

Title

Number of Seizure-free Participants at Baseline Who Remained Seizure-free Throughout the Entire Treatment Period

Description

Participants were considered to be seizure-free if they did not report any seizures at Baseline.

Time Frame

Week 30 or 33

Title

Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale

Description

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])

Title

Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale

Description

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])

Title

Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points in the Study

Description

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])

Title

Change From Baseline in the Height at the Indicated Time Points in the Study

Description

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.

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])

Title

Change From Baseline in the Weight at the Indicated Time Points in the Study

Description

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.

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])

Title

Description

Time Frame