Lamotrigine Extended-Release In Elderly Patients With Epilepsy

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.

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

Population: Safety Population: all participants who were enrolled and took at least one dose of study drug

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.

Time frame: Weeks 4, 7, 11, 15, 20, 24, and 28

Population: Safety Population. Participants with missing data were not analyzed. Not all participants received all doses at each blood draw; therefore, participants were only analyzed for the dose received at blood draw.

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.

Time frame: Weeks 4, 7, 11, 15, 20, 24, and 28

Population: Safety Population. Participants with missing data were not analyzed. Not all participants received all doses at each blood draw; therefore, participants were only analyzed for the dose received at blood draw.

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.

Time frame: Weeks 4, 7, 11, 15, 20, 24, and 28

Population: Safety Population. Participants with missing data were not analyzed. Not all participants received all doses at each blood draw; therefore, participants were only analyzed for the dose received at blood draw.

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.

Time frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)

Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.

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.

Time frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)

Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.

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.

Time frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)

Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.

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.

Time frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)

Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.

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.

Time frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)

Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.

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.

Time frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)

Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.

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.

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])

Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.

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.

Time frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)

Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.

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])

Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.

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.

Time frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)

Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.

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])

Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.

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.

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])

Population: Safety Population. Participants with missing data were not analyzed.

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.

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])

Population: Safety Population. Only those participants who had seizures at baseline were analyzed.

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.

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)

Population: Safety Population. Only those participants who had seizures at baseline were analyzed.

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

Time frame: Week 30 or 33

Population: Safety Population. Participants who were seizure-free at Baseline were analyzed.

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.

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)

Population: Safety Population. Only those participants who had seizures at baseline were analyzed.

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.

Time frame: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)

Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.

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.

Time frame: Weeks 4, 7, 11, 15, 20, 24, and 28

Population: Safety Population. Participants with missing data were not analyzed. Not all participants received all doses at each blood draw; therefore, participants were only analyzed for the dose received at blood draw.