A Phase 3 interventional study of lamotrigine (LAMICTAL) extended-release and Placebo in Epilepsy, Tonic-Clonic, sponsored by GlaxoSmithKline. Completed at 146 sites in 11 countries. Open to participants aged 13 Years and older. Per ClinicalTrials.gov, last updated 2017-01-02.
Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Treatment
Among 11 studies in Epilepsy, Tonic-Clonic with a site in United States — 1 open to participants now, 2 under way, 2 of them phase 3. Epilepsy, Tonic-Clonic · United States.
Among the 11 studies in Epilepsy, Tonic-Clonic with a site in United States, this one is the 4th largest by enrollment of the 10 interventional ones that give a count, is the only one that started in 2004, is one of 3 in phase 3, and was the 3rd registered.
23 studies on the registry are indexed under Epilepsy, Tonic-Clonic; 3 are open to participants now.
This study's enrollment of 153 is above the median of 94 across 20 interventional studies indexed under Epilepsy, Tonic-Clonic.
Browse Epilepsy, Tonic-Clonic studies →1 of the 11 studies in Epilepsy, Tonic-Clonic with a site in United States is open now.
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 2 Epilepsy, Tonic-Clonic studies recruiting now, 1 (50%) set no upper age limit and 1 (50%) stop at 75 or younger; 1 take children under 18; 1 take healthy volunteers.
This study: 13 Years and older · all sexes · no healthy volunteers.
The full table on the hub →11 studies; the count open now beside each. This study's row is marked.
First in 2000; this study’s year is marked. 1 started in 2004.
Median enrollment 134 across the 10 interventional studies, 1,278 across the 1 observational. Of the 9 that completed or were terminated, 3 (33%) have results posted.
8 of 11 have an industry lead sponsor. The 10 most frequent:
GlaxoSmithKline is the lead sponsor of 3,650 studies on the registry; 118 are open to participants now.
Of its 264 completed or terminated interventional studies of FDA-regulated products, 241 (91%) have results posted.
GlaxoSmithKline has 3 studies filed under Epilepsy, Tonic-Clonic — fewer than ten, so there is no comparison to draw.
1 of the studies in Epilepsy, Tonic-Clonic with a site in United States that are under way reach primary completion within a year, 1 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT05064878Phase 3Zogenix, Inc.A Phase 3 Study to Examine the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder. | 2027-11-08 |
Among the 11 studies in Epilepsy, Tonic-Clonic with a site in United States, from their registry updates:
Nothing recorded among them since 2026-09-25.
This study is being conducted to compare the efficacy and safety of LAMICTAL (lamotrigine) extended-release with placebo in the treatment of Primary Generalized Tonic-Clonic (PGTC) seizures. LAMICTAL extended-release is an investigational drug. Placebo tablets look like LAMICTAL extended-release tablets but do not contain active medication. In this study, LAMICTAL extended-release or placebo tablets will be added to current seizure treatments.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Has at least 3 PGTC seizures occurring anytime during an 8-week (i.e., 56 days) prospective Baseline Phase.
NOTE: With authorization from GSK, a maximum of four weeks (i.e., 28 days) of historical seizure data may replace up to four weeks (i.e., 28 days) of the prospective Baseline Phase for subjects providing reliable documentation of the following:
Is currently treated with a stable regimen of one or two AED(s) for at least four weeks prior to starting the Baseline Phase (historical or prospective).
NOTE: Subjects with surgically implanted vagal nerve stimulators (VNS) will be allowed to enter the study provided that all of the following conditions are met:
If female, and of , must be using an acceptable form of , to include one of the following:
Consistent and correct use of one of the following methods of birth control:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Placebo
Drug: lamotrigine (LAMICTAL) extended-release
Primary experimental dosage form
Placebo control
Percent Change From Baseline in Weekly Primary Generalized Tonic-clonic (PGTC) Seizure Frequency During the Entire Double-Blind Treatment Phase
Percent change from baseline is calculated as the number of seizures by week during the Double-Blind Treatment Phase (Treatment Week 1 up to Week 19) compared to the number of seizures per week during the Baseline Phase (Baseline Week 1 up to Week 8). A positive number equals a reduction in seizure frequency. PGTC seizures are more commonly known as gran mal seizures.
Time frame: Baseline through end of Double-Blind Treatment Phase (up to Week 19)
Number of Participants With >=25%, >=50%, >=75%, or 100% Reduction in PGTC Seizure Frequency During the Entire Double-Blind (DB)Treatment Phase (TP), the Escalation Phase, the Maintenance Phase, and the Last 8 Weeks of the Maintenance Phase
Change in seizure frequency was calculated as the average seizure frequency during each of the following: the Entire DB Treatment Phase (Treatment Week 1 up to Week 19); the Escalation Phase (Treatment Week 1 up to Week 7); the Maintenance Phase (Treatment Week 8 up to Week 19); and the last 8 weeks of the Maintenance Phase (Treatment Week 12 up to Week 19), minus the seizure frequency at Baseline.
Time frame: Entire DB Treatment Phase (Treatment Week 1 up to Week 19), Escalation Phase (Treatment Week 1 up to Week 7), Maintenance Phase (Treatment Week 8 up to Week 19), and the last 8 weeks of the Maintenance Phase (Treatment Week 12 up to Week 19)
Percent Change From Baseline in PGTC Seizure Frequency During the Escalation Phase, the Maintenance Phase, and During the Last 8 Weeks of the Maintenance Phase of the Double-Blind Treatment Phase
Percent change from baseline is calculated as the number of seizures by week during the Escalation Phase (Treatment Week 1 up to Week 7), the Maintenance Phase (Treatment Week 8 up to Week 19), and during the last 8 weeks of the Maintenance Phase (Treatment Week 12 up to Week 19) compared to the number of seizures per week during the Baseline Phase (Baseline Week 1 up to Week 8). A positive number equals a reduction in seizure frequency.
Time frame: Escalation Phase (Treatment Week 1 up to Week 7), Maintenance Phase (Treatment Week 8 up to Week 19), and the last 8 weeks of the Maintenance Phase (Week 12 up to Week 19)
Number of Participants With the Indicated Time to >=50% Reduction in Seizure Frequency in the Double-Blind Treatment Phase
50% reduction in seizure frequency is defined as the time at which a participant first achieved and maintained a \>=50% reduction in seizure frequency following exposure to at least 1 week of study drug.
Time frame: Baseline through end of Double-Blind Treatment Phase (up to Week 19)
Change From Baseline in Body Weight at Week 19 of the Double-Blind Treatment Phase
Change from baseline in body weight is calculated as the Week 19 (or last on-study measurement in Double-Blind Treatment Phase) value minus the Baseline value.
Time frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
Number of Participants With Improved Clinical Status on the Investigator's Global Assessment in the Double-Blind Treatment Phase
The investigators rated the participants' overall clinical status based on 7 clinical factors and an overall factor: seizure frequency, duration, and intensity; adverse experiences; social, intellectual, and motor functioning. Using a 7-point scale (marked deterioration \[1\], moderate deterioration \[2\], mild deterioration \[3\], no change \[4\], mild improvement \[5\], moderate improvement \[6\], or marked improvement \[7\]), the investigators assessed the participants' status compared to their condition prior to initiating study medication.
Time frame: Week 19 (or last on-study assessment in Double-Blind Treatment Phase)
Number of Participants With Improved Satisfaction With Seizure Control on the Subject Satisfaction Questionnaire in the Double-Blind Treatment Phase
Participants were asked to rate their satisfaction with their seizure control compared to their seizure control prior to initiating study drug on a 7 point scale: marked deterioration (1), moderate deterioration (2), mild deterioration (3), no change (4), mild improvement (5), moderate improvement (6), or marked improvement (7).
Time frame: Week 19 (or last on-study assessment in Double-Blind Treatment Phase)
Percent Change From Baseline in Weekly PGTC Seizure Frequency During the Entire Continuation Phase (CP), the Transition Phase, the Open-Label Phase, and the Last 8 Weeks of the Open-Label Phase
Percent change from baseline is calculated as the number of seizures by week during the entire CP (CP Week 1 up to Week 52), the Transition Phase (CP Week 1 up to Week 7), the Open-Label Phase (CP Week 8 up to Week 52), and the last 8 weeks of the Open-Label Phase (CP Week 45 up to Week 52) minus the number of seizures per week during the Baseline Phase (Baseline Week 1 through Week 8). A positive number equals a reduction in seizure frequency.
Time frame: Entire CP (CP Week 1 up to Week 52), the Transition Phase (CP Week 1 up to Week 7), the Open-Label Phase (CP Week 8 up to Week 52), and the last 8 weeks of the Open-Label Phase (CP Week 45 up to Week 52)
Number of Participants With >=25%, >=50%, >=75%, or 100% Reduction or >=50% Increase From Baseline in Weekly PGTC Seizure Frequency for the Entire Continuation Phase, the Transition Phase, the Open-Label (OL) Phase, and the Last 8 Weeks of the OL Phase.
Change in seizure frequency was calculated as the average seizure frequency during each of the following: the Entire CP (CP Week 1 up to Week 52); the Transition Phase (CP Week 1 up to Week 7); the Open-Label (OL) Phase (CP Week 8 up to Week 52); and the last 8 weeks of the Open Label Phase (CP Week 45 up to Week 52) minus the seizure frequency at Baseline. W, Week.
Time frame: Entire CP (CP Week 1 up to Week 52), the Transition Phase (CP Week 1 up to Week 7), the Open-Label Phase (CP Week 8 up to Week 52), and the last 8 weeks of the Open-Label Phase (CP Week 45 up to Week 52)
Mean Change From Baseline in the Profile of Mood State (POMS) Mood Disturbance Total Score at Week 19 of the Double-Blind Treatment Phase
The POMS is a self-administered 65-item questionnaire that evaluates the participants' perception of their mood state in 6 areas: tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment. Items are rated on a 5-point Likert scale from 0 (not at all) to 4 (extremely), with higher scores indicating a more negative mood state. A total score (from 0 to 24) is obtained by summing the scores of the six domains.
Time frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
Mean Change From Baseline in the Center for Epidemiological Studies-Depression Scale (CES-D) Total Score at Week 19 of the Double-Blind Treatment Phase
The 20-item CES-D questionnaire is self-administered and asks respondents to report the frequency to which the 20 events were experienced over the past week. A 4-point Likert scale is used and ranges from rarely or none of the time (0) to most or all of the time (3). The total score, a sum across the 20 items (ranging from 0 to 60), determines the extent to which a participant may be experiencing depression. Higher scores indicate a higher severity of depression.
Time frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
Mean Change From Baseline in the Neurological Disorders Depression Inventory-Epilepsy (NDDI-E) 6-Item Total Score at Week 19 of the Double-Blind Treatment Phase
The NDDI-E is a self-reported questionnaire composed of 46 brief phrases/words to identify mood disorders across the spectrum of depression. It was developed to capture depressive moods that are co-morbid with the disease of epilepsy or its treatment as well as to measure the depressive state of the participant. All phrases are measured on a 4-point Likert scale of Never (1) to Always/often (4) and refer to the participants' mood over the past week. Scoring is comprised of a total mood score calculated by summing the scores of 6 specific items (from 6=never to 24=always or often).
Time frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
Mean Change From Baseline in the Quality of Life in Epilepsy-31-P (QOLIE-31P) Overall Score at Week 19 of the Double-Blind Treatment Phase
The QOLIE-31 is a 31-item questionnaire that evaluates the participants' perception of his or her quality of life in 7 domains: seizure worry, emotional well being, energy/fatigue, cognitive functioning, medication effects, social functioning, and overall quality of life. Each domain (with scores ranging from 0 to 100) is summed and divided by the total number of questions that were answered. The overall score is derived by weighting and then summing up the seven domain scores.
Time frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
Mean Change From Baseline in the Adverse Experience Profile (AEP) Total Score at Week 19 of the Double-Blind Treatment Phase
The AEP is a list of 19 items covering many possible side effects attributable to drug treatment. The participants respond by assessing how much each event has been a problem for them over the past 4 weeks (1=Never a Problem to 4=Always a Problem). Each individual item can be examined; an overall adverse events score is calculated as the sum of the scores across the 19 items. The AEP total score ranges from 19 to 76, with a higher score indicating a higher degree of adverse event severity.
Time frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
Mean Change From Baseline in the Seizure Severity Questionnaire (SSQ) Global Bother Score at Week 19 Double-Blind Treatment Phase
The SSQ is a self-reported instrument developed to assess the severity of seizures and seizure symptoms. The scale consists of 10 major clinical features/symptoms of seizures that the participants rate on a 7-point Likert scale (ranging from very mild/helpful/no bother at all \[1\] to very severe/no help/bothersome \[7\]). The Global Bother Domain is the primary score used for the analysis of the SSQ and has scores ranging from 1 to 7.
Time frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
Mean Change From Baseline in the Epworth Sleepiness Scale (ESS) 8-Item Total Score at Week 19 of the Double-Blind Treatment Phase
The ESS is an 8-item, self-administered questionnaire that measures excessive daytime sleepiness in adults. The instrument captures information on the extent to which the participant would be likely, or not, to fall asleep in certain situations. The stimulus question is: How likely are you to doze off or fall asleep in the following situations, in contrast to feeling just tired? Questions are answered on a 4-point scale (would never doze \[0\] to high chance of dozing \[3\]). The total score ranges from 0 to 24, where a higher score indicates a higher chance of dozing.
Time frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
Serum Concentrations and Population (POP) Pharmacokinetic Parameters for Lamotrigine
Serum samples for participants on lamotrigine were analyzed with a validated analytical method based on solid phase extraction of serum followed by High-Performance Liquid Chromatography (HPLC) Mass Spectrometry (MS)/MS analysis. The lower limit of quantification (LLQ) for serum lamotrigine was 4 nanograms (ng)/milliliter (mL), using a 50 microliter (µL) aliquot of human serum with a higher limit of quantification (HLQ) of 4,000 ng/mL. PK data cannot be reported, as PK data from several different studies have been combined into one POP/PK analysis and cannot be separated by study.
Time frame: Blood samples drawn at Treatment Weeks 11, 15, and 19 (or last on-study measurement in Double-Blind Treatment Phase)
All participants (par.) that complete the Treatment Phase (TP) and all Baseline Failures (par. who did not meet randomization seizure criteria necessary to qualify for the TP) are eligible to enter the Continuation Phase (CP). The CP is for long-term safety exposure to lamotrigine (LTG) extended release (XR); it is not a cross-over phase.
| Milestone | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR | Continuation Phase: Placebo/LTG | Continuation Phase: LTG/LTG | Baseline Failures |
|---|---|---|---|---|---|
| Started | 77 | 76 | 0 | 0 | 0 |
| Completed | 69 | 66 | 0 | 0 | 0 |
| Not completed | 8 | 10 | 0 | 0 | 0 |
| Withdrew: Adverse event | 2 | 1 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Protocol violation | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 2 | 3 | 0 | 0 | 0 |
| Withdrew: Pregnancy | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Participant did not take drug | 3 | 4 | 0 | 0 | 0 |
| Milestone | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR | Continuation Phase: Placebo/LTG | Continuation Phase: LTG/LTG | Baseline Failures |
|---|---|---|---|---|---|
| Started | 0 | 0 | 69 | 67 | 32 |
| Completed | 0 | 0 | 63 | 65 | 27 |
| Not completed | 0 | 0 | 6 | 2 | 5 |
| Withdrew: Adverse event | 0 | 0 | 2 | 0 | 2 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 2 | 1 | 1 |
| Withdrew: Pregnancy | 0 | 0 | 1 | 1 | 0 |
| Withdrew: Non-compliance | 0 | 0 | 0 | 0 | 1 |
Percent change from baseline is calculated as the number of seizures by week during the Double-Blind Treatment Phase (Treatment Week 1 up to Week 19) compared to the number of seizures per week during the Baseline Phase (Baseline Week 1 up to Week 8). A positive number equals a reduction in seizure frequency. PGTC seizures are more commonly known as gran mal seizures.
| percent change | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| Percent Change From Baseline in Weekly Primary Generalized Tonic-clonic (PGTC) Seizure Frequency During the Entire Double-Blind Treatment Phase | 32.1 (-427 to 100) | 75.4 (-100 to 100) |
Change in seizure frequency was calculated as the average seizure frequency during each of the following: the Entire DB Treatment Phase (Treatment Week 1 up to Week 19); the Escalation Phase (Treatment Week 1 up to Week 7); the Maintenance Phase (Treatment Week 8 up to Week 19); and the last 8 weeks of the Maintenance Phase (Treatment Week 12 up to Week 19), minus the seizure frequency at Baseline.
| participants | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| >=25% reduction, Entire DB TP, n=72, 69 | 43 | 56 |
| >=50% reduction, Entire DB TP, n=72, 69 | 23 | 48 |
| >=75% reduction, Entire DB TP, n=72, 69 | 14 | 35 |
| 100% reduction, Entire DB TP, n=72, 69 | 7 | 14 |
| >=25% reduction, Escalation Phase, n=72, 69 | 39 | 51 |
| >=50% reduction, Escalation Phase, n=72, 69 | 23 | 38 |
| >=75% reduction, Escalation Phase, n=72, 69 | 14 | 24 |
| 100% reduction, Escalation Phase, n=72, 69 | 9 | 15 |
| >=25% reduction, Maintenance Phase, n=70, 68 | 46 | 60 |
| >=50% reduction, Maintenance Phase, n=70, 68 | 29 | 51 |
| >=75% reduction, Maintenance Phase, n=70, 68 | 14 | 40 |
| 100% reduction, Maintenance Phase, n=70, 68 | 10 | 31 |
| >=25% reduction, Last 8 Weeks of MP, n=70, 68 | 47 | 61 |
| >=50% reduction, Last 8 Weeks of MP, n=70, 68 | 29 | 54 |
| >=75% reduction, Last 8 Weeks of MP, n=70, 68 | 18 | 44 |
| 100% reduction, Last 8 Weeks of MP, n=70, 68 | 15 | 35 |
Percent change from baseline is calculated as the number of seizures by week during the Escalation Phase (Treatment Week 1 up to Week 7), the Maintenance Phase (Treatment Week 8 up to Week 19), and during the last 8 weeks of the Maintenance Phase (Treatment Week 12 up to Week 19) compared to the number of seizures per week during the Baseline Phase (Baseline Week 1 up to Week 8). A positive number equals a reduction in seizure frequency.
| percent change | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| Escalation Phase, n=72, 69 | 30.6 (-319 to 100) | 61.9 (-197 to 100) |
| Maintenance Phase, n=70, 68 | 33.3 (-492 to 100) | 89.7 (-142 to 100) |
| Last 8 weeks of the Maintenance Phase, n=70, 68 | 35.4 (-180 to 100) | 100.0 (-131 to 100) |
50% reduction in seizure frequency is defined as the time at which a participant first achieved and maintained a \>=50% reduction in seizure frequency following exposure to at least 1 week of study drug.
| participants | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| 2 weeks | 12 | 22 |
| 4 weeks | 12 | 28 |
| 8 weeks | 14 | 39 |
| 12 weeks | 20 | 43 |
| 16 weeks | 23 | 48 |
Change from baseline in body weight is calculated as the Week 19 (or last on-study measurement in Double-Blind Treatment Phase) value minus the Baseline value.
| kilograms | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| Change From Baseline in Body Weight at Week 19 of the Double-Blind Treatment Phase | 1.00 (-7.7 to 10.0) | 0.00 (-11.4 to 8.8) |
The investigators rated the participants' overall clinical status based on 7 clinical factors and an overall factor: seizure frequency, duration, and intensity; adverse experiences; social, intellectual, and motor functioning. Using a 7-point scale (marked deterioration \[1\], moderate deterioration \[2\], mild deterioration \[3\], no change \[4\], mild improvement \[5\], moderate improvement \[6\], or marked improvement \[7\]), the investigators assessed the participants' status compared to their condition prior to initiating study medication.
| participants | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| Any improvement, score of 5-7 | 36 | 57 |
| No change, score of 4 | 33 | 10 |
| Any deterioration, score of 1-3 | 2 | 1 |
Participants were asked to rate their satisfaction with their seizure control compared to their seizure control prior to initiating study drug on a 7 point scale: marked deterioration (1), moderate deterioration (2), mild deterioration (3), no change (4), mild improvement (5), moderate improvement (6), or marked improvement (7).
| participants | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| Any improvement, score of 5-7 | 53 | 60 |
| No change, score of 4 | 13 | 6 |
| Any deterioration, score of 1-3 | 5 | 2 |
Percent change from baseline is calculated as the number of seizures by week during the entire CP (CP Week 1 up to Week 52), the Transition Phase (CP Week 1 up to Week 7), the Open-Label Phase (CP Week 8 up to Week 52), and the last 8 weeks of the Open-Label Phase (CP Week 45 up to Week 52) minus the number of seizures per week during the Baseline Phase (Baseline Week 1 through Week 8). A positive number equals a reduction in seizure frequency.
| percent change | Continuation Phase: Placebo/LTG | Continuation Phase: LTG/LTG | Baseline Failures |
|---|---|---|---|
| Entire Continuation Phase, n=68, 66, 24 | 85.2 (-113.3 to 100.0) | 95.1 (-100.0 to 100.0) | 21.7 (-115.4 to 100.0) |
| Transition Phase, n=68, 66, 20 | 73.1 (-90.5 to 100.0) | 100.0 (-100.0 to 100.0) | 100.0 (-100.0 to 100.0) |
| Open-Label Phase, n=68, 64, 23 | 89.2 (-116.7 to 100.0) | 95.0 (-100.0 to 100.0) | 31.7 (-194.7 to 100.0) |
| Last 8 weeks of Open-Label Phase, n=68, 63, 19 | 100.0 (-184.2 to 100.0) | 100.0 (-53.3 to 100.0) | 100.0 (-500.0 to 100.0) |
Change in seizure frequency was calculated as the average seizure frequency during each of the following: the Entire CP (CP Week 1 up to Week 52); the Transition Phase (CP Week 1 up to Week 7); the Open-Label (OL) Phase (CP Week 8 up to Week 52); and the last 8 weeks of the Open Label Phase (CP Week 45 up to Week 52) minus the seizure frequency at Baseline. W, Week.
| participants | Continuation Phase: Placebo/LTG | Continuation Phase: LTG/LTG | Baseline Failures |
|---|---|---|---|
| >=25% reduction, Entire CP, n=68, 66, 24 | 59 | 63 | 11 |
| >=50% reduction, Entire CP, n=68, 66, 24 | 57 | 59 | 11 |
| >=75% reduction, Entire CP, n=68, 66, 24 | 46 | 49 | 8 |
| 100% reduction, Entire CP, n=68, 66, 24 | 16 | 28 | 6 |
| >=50% increase, Entire CP, n=68, 66, 24 | 2 | 1 | 10 |
| >=25% reduction, Transition Phase, n=68, 66, 20 | 51 | 60 | 13 |
| >=50% reduction, Transition Phase, n=68, 66, 20 | 44 | 56 | 12 |
| >=75% reduction, Transition Phase, n=68, 66, 20 | 33 | 46 | 12 |
| 100% reduction, Transition Phase, n=68, 66, 20 | 27 | 41 | 12 |
| >=50% increase, Transition Phase, n=68, 66, 20 | 3 | 1 | 3 |
| >=25% reduction, Open-Label Phase, n=68, 64, 23 | 61 | 61 | 12 |
| >=50% reduction, Open-Label Phase, n=68, 64, 23 | 56 | 57 | 10 |
| >=75% reduction, Open-Label Phase, n=68, 64, 23 | 47 | 49 | 8 |
| 100% reduction, Open-Label Phase, n=68, 64, 23 | 21 | 28 | 6 |
| >=50% increase, Open-Label Phase, n=68, 64, 23 | 2 | 1 | 10 |
| >=25% reduction, Last 8 W of OL Phase,n=68, 63, 19 | 60 | 60 | 10 |
| >=50% reduction, Last 8 W of OL Phase,n=68, 63, 19 | 53 | 53 | 10 |
| >=75% reduction, Last 8 W of OL Phase,n=68, 63, 19 | 45 | 47 | 10 |
| 100% reduction, Last 8 W of OL Phase, n=68, 63, 19 | 35 | 41 | 10 |
| >=50% increase, Last 8 W of OL Phase, n=68, 63, 19 | 2 | 1 | 4 |
The POMS is a self-administered 65-item questionnaire that evaluates the participants' perception of their mood state in 6 areas: tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment. Items are rated on a 5-point Likert scale from 0 (not at all) to 4 (extremely), with higher scores indicating a more negative mood state. A total score (from 0 to 24) is obtained by summing the scores of the six domains.
| points on a scale | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| Mean Change From Baseline in the Profile of Mood State (POMS) Mood Disturbance Total Score at Week 19 of the Double-Blind Treatment Phase | 2.4 ± 6.97 | 9.7 ± 8.65 |
The 20-item CES-D questionnaire is self-administered and asks respondents to report the frequency to which the 20 events were experienced over the past week. A 4-point Likert scale is used and ranges from rarely or none of the time (0) to most or all of the time (3). The total score, a sum across the 20 items (ranging from 0 to 60), determines the extent to which a participant may be experiencing depression. Higher scores indicate a higher severity of depression.
| points on a scale | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| Mean Change From Baseline in the Center for Epidemiological Studies-Depression Scale (CES-D) Total Score at Week 19 of the Double-Blind Treatment Phase | 2.9 ± 2.81 | 2.4 ± 2.54 |
The NDDI-E is a self-reported questionnaire composed of 46 brief phrases/words to identify mood disorders across the spectrum of depression. It was developed to capture depressive moods that are co-morbid with the disease of epilepsy or its treatment as well as to measure the depressive state of the participant. All phrases are measured on a 4-point Likert scale of Never (1) to Always/often (4) and refer to the participants' mood over the past week. Scoring is comprised of a total mood score calculated by summing the scores of 6 specific items (from 6=never to 24=always or often).
| points on a scale | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| Mean Change From Baseline in the Neurological Disorders Depression Inventory-Epilepsy (NDDI-E) 6-Item Total Score at Week 19 of the Double-Blind Treatment Phase | -0.1 ± 0.98 | -2.4 ± 1.24 |
The QOLIE-31 is a 31-item questionnaire that evaluates the participants' perception of his or her quality of life in 7 domains: seizure worry, emotional well being, energy/fatigue, cognitive functioning, medication effects, social functioning, and overall quality of life. Each domain (with scores ranging from 0 to 100) is summed and divided by the total number of questions that were answered. The overall score is derived by weighting and then summing up the seven domain scores.
| points on a scale | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| Mean Change From Baseline in the Quality of Life in Epilepsy-31-P (QOLIE-31P) Overall Score at Week 19 of the Double-Blind Treatment Phase | -6.5 ± 3.97 | -8.5 ± 4.35 |
The AEP is a list of 19 items covering many possible side effects attributable to drug treatment. The participants respond by assessing how much each event has been a problem for them over the past 4 weeks (1=Never a Problem to 4=Always a Problem). Each individual item can be examined; an overall adverse events score is calculated as the sum of the scores across the 19 items. The AEP total score ranges from 19 to 76, with a higher score indicating a higher degree of adverse event severity.
| points on a scale | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| Mean Change From Baseline in the Adverse Experience Profile (AEP) Total Score at Week 19 of the Double-Blind Treatment Phase | 3.0 ± 2.16 | 1.4 ± 2.77 |
The SSQ is a self-reported instrument developed to assess the severity of seizures and seizure symptoms. The scale consists of 10 major clinical features/symptoms of seizures that the participants rate on a 7-point Likert scale (ranging from very mild/helpful/no bother at all \[1\] to very severe/no help/bothersome \[7\]). The Global Bother Domain is the primary score used for the analysis of the SSQ and has scores ranging from 1 to 7.
| points on a scale | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| Mean Change From Baseline in the Seizure Severity Questionnaire (SSQ) Global Bother Score at Week 19 Double-Blind Treatment Phase | 0.86 ± 0.84 | 1.23 ± 1.08 |
The ESS is an 8-item, self-administered questionnaire that measures excessive daytime sleepiness in adults. The instrument captures information on the extent to which the participant would be likely, or not, to fall asleep in certain situations. The stimulus question is: How likely are you to doze off or fall asleep in the following situations, in contrast to feeling just tired? Questions are answered on a 4-point scale (would never doze \[0\] to high chance of dozing \[3\]). The total score ranges from 0 to 24, where a higher score indicates a higher chance of dozing.
| points on a scale | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR |
|---|---|---|
| Mean Change From Baseline in the Epworth Sleepiness Scale (ESS) 8-Item Total Score at Week 19 of the Double-Blind Treatment Phase | -0.6 ± 0.69 | 1.0 ± 0.67 |
Serum samples for participants on lamotrigine were analyzed with a validated analytical method based on solid phase extraction of serum followed by High-Performance Liquid Chromatography (HPLC) Mass Spectrometry (MS)/MS analysis. The lower limit of quantification (LLQ) for serum lamotrigine was 4 nanograms (ng)/milliliter (mL), using a 50 microliter (µL) aliquot of human serum with a higher limit of quantification (HLQ) of 4,000 ng/mL. PK data cannot be reported, as PK data from several different studies have been combined into one POP/PK analysis and cannot be separated by study.
No measurements were reported for this outcome.
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Double-Blind Phase: Placebo | — | 0/74 (0%) | 21/74 (28.4%) |
| Double-Blind Phase: LTG XR | — | 1/72 (1.4%) | 27/72 (37.5%) |
| Continuation Phase: Placebo/LTG | — | 3/69 (4.3%) | 29/69 (42%) |
| Continuation Phase: LTG/LTG | — | 3/67 (4.5%) | 21/67 (31.3%) |
| Baseline Failures | — | 1/32 (3.1%) | 18/32 (56.3%) |
| Event | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR | Continuation Phase: Placebo/LTG | Continuation Phase: LTG/LTG | Baseline Failures |
|---|---|---|---|---|---|
| AtaxiaNervous system disorders | 0/74 | 0/72 | 0/69 | 0/67 | 1/32 |
| NystagmusNervous system disorders | 0/74 | 0/72 | 0/69 | 0/67 | 1/32 |
| Suicide attemptPsychiatric disorders | 0/74 | 0/72 | 0/69 | 0/67 | 1/32 |
| Abdominal painGastrointestinal disorders | 0/74 | 0/72 | 0/69 | 0/67 | 1/32 |
| NauseaGastrointestinal disorders | 0/74 | 0/72 | 0/69 | 0/67 | 1/32 |
| VomitingGastrointestinal disorders | 0/74 | 0/72 | 0/69 | 0/67 | 1/32 |
| Syncope vasovagalNervous system disorders | 0/74 | 0/72 | 0/69 | 1/67 | 0/32 |
| Uterine leiomyomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/74 | 0/72 | 0/69 | 1/67 | 0/32 |
| Abortion spontaneousPregnancy, puerperium and perinatal conditions | 0/74 | 0/72 | 0/69 | 1/67 | 0/32 |
| Altered state of consciousnessNervous system disorders | 0/74 | 0/72 | 1/69 | 0/67 | 0/32 |
| Event | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR | Continuation Phase: Placebo/LTG | Continuation Phase: LTG/LTG | Baseline Failures |
|---|---|---|---|---|---|
| HeadacheNervous system disorders | 12/74 | 10/72 | 11/69 | 5/67 | 9/32 |
| DizzinessNervous system disorders | 5/74 | 4/72 | 7/69 | 4/67 | 7/32 |
| NauseaGastrointestinal disorders | 4/74 | 5/72 | 1/69 | 1/67 | 5/32 |
| PyrexiaGeneral disorders | 4/74 | 5/72 | 7/69 | 5/67 | 3/32 |
| VomitingGastrointestinal disorders | 3/74 | 7/72 | 5/69 | 2/67 | 2/32 |
| TremorNervous system disorders | 0/74 | 4/72 | 5/69 | 3/67 | 3/32 |
| FatigueGeneral disorders | 2/74 | 1/72 | 1/69 | 0/67 | 3/32 |
| All rashSkin and subcutaneous tissue disorders | 4/74 | 2/72 | 2/69 | 1/67 | 2/32 |
| DiplopiaEye disorders | 1/74 | 4/72 | 4/69 | 1/67 | 2/32 |
| AtaxiaNervous system disorders | 0/74 | 0/72 | 2/69 | 2/67 | 2/32 |
| Age, Continuous(years) | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR | Total |
|---|---|---|---|
| Mean | 28.4 ± 11.48 | 29.4 ± 12.78 | 28.9 ± 12.10 |
| Gender(Participants) | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR | Total |
|---|---|---|---|
| Female | 38 | 32 | 70 |
| Male | 35 | 38 | 73 |
| Race/Ethnicity, Customized(participants) | Double-Blind Phase: Placebo | Double-Blind Phase: LTG XR | Total |
|---|---|---|---|
| African American/African Heritage | 1 | 2 | 3 |
| Asian | 31 | 31 | 62 |
| White | 38 | 37 | 75 |
| American Indian or Alaskan Native and White | 2 | 0 | 2 |
| Asian and White | 1 | 0 | 1 |
Showing the first 100 of 146 sites across 11 countries. Choose a country and city above to see the rest.
Plan to share: Yes — Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
The record gives a start of Dec 2004, a primary completion of Jul 2008 and a completion of Jul 2008. It does not say whether these dates are actual or estimated.
Results were first posted in May 2010, 1 year 10 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Nov 2016. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Lamotrigine