Valproate Dose Reduction and Its Clinical Evaluation by Introducing Lamotrigine in Japanese Women With Epilepsy - Single Arm, Multicenter, and Open-label Study

NCT02100644 | Completed Phase 4 Results

• 1 other identifier: 200776
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to examine whether the VPA (Valproate) dose can be reduced by additional administration of LTG (Lamotrigine) in Japanese pre-menopausal female epilepsy patients aged 15 years or older, whose seizures are well controlled by VPA monotherapy.

Conditions

Epilepsy

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Achieved Reduction in Daily VPA Dose

  The VPA dose reduction from Baseline is defined as post VPA dose minus the Baseline VPA dose \< 0. Baseline VPA dose is the dose at the Baseline visit (Week 0) and the post VPA dose is the last VPA dose during the LTG and VPA Maintenance Phase. Percentage of participants with dose reduction during the LTG and VPA Maintenance Phase is presented.

  Baseline and at the end of the LTG and VPA Maintenance Phase, 24-46 weeks that can be varied by durations of the LTG Escalation Phase and VPA Reduction Phase

• Percent Change in the VPA Dose

  Percent change in VPA dose is calculated as (pre-dose - post-dose) / pre-dose x 100. Pre-dose is the VPA dose at the Baseline visit and post-dose is the last VPA dose during the LTG and VPA Maintenance Phase.

  Baseline and at the end of the LTG and VPA Maintenance Phase, 24-46 weeks that can be varied by durations of the LTG Escalation Phase and VPA Reduction Phase

Secondary Outcomes (5)

• Number of Days in Total That Epileptic Seizures Occurred up to the LTG and VPA Maintenance Phase

  Baseline and up to 46 weeks

• Change From Baseline in Quality of Life in Epilepsy-31-P (QOLIE-31-P) in Participants Aged 18 Years and Older

  Baseline and up to 46 weeks

• Change From Baseline in Quality of Life in Epilepsy for Adolescents (QOLIE-AD-48) in Participants Aged 15-17 Years

  Baseline and up to 46 weeks

• Percentage of Participants Who Completed or Discontinued From the Study

  Up to 50 weeks

• Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation of the Investigational Product and/or Withdrawal From the Study, Drug-related AEs, Deaths and Serious Adverse Events (SAEs) Throughout the Study

  From the start of study treatment until follow-up (up to 50 weeks)

Study Arms (1)

Lamotrigine

EXPERIMENTAL

The study objective is to examine whether the VPA dose can be reduced by additional administration of LTG in Japanese pre-menopausal female epilepsy patients, whose seizures are well controlled by VPA monotherapy. Then VPA is the standard product in this stuudy, not the investigational product.

Drug: Lamotrigine tablets 25/100 mg

Interventions

Lamotrigine tablets 25/100 mg DRUG

Lamotrigine (LTG) is administered according to the package insert: that is, 25 mg of LTG will be orally administered once every other day for the first 2 weeks and then once daily for the next 2 weeks. Thereafter, the dose will be gradually escalated by 25-50 mg every 1-2 week for once or twice daily administration. During the VPA reduction phase and LTG\&amp;VPA maintenance phase, as specified in the information of package insert, maintenance dose of LTG will be administered twice daily.

Lamotrigine

Eligibility Criteria

• Age: 15 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• (Target disease) Epilepsy patients having the following seizure types as classified by the International Classification of Epileptic Seizures
• Partial seizures (with or without secondary generalization)
• Tonic-clonic seizures with or without myoclonus but without other generalized seizure type(s)
• Subjects having a confident diagnosis of epilepsy that is uncomplicated by pseudoseizures such as psychogenic nonepileptic seizures
• Subjects whose seizures have been controlled for 12 weeks prior to start of the investigational product with a stable maintenance dose of VPA monotherapy (400-1200 mg/d)
• (Age and gender)
• Japanese pre-menopausal women who are at least 15 years old at the time of consent, not lactating, and can agree to use any of the following types of contraception in a reliable fashion:
• Complete abstinence during the study as well as for a period after the study to account for elimination of the investigational product (a minimum of 2 weeks)
• Consistent and correct use of any of the following contraceptive methods
• Surgical sterilization of male partner (i.e., male partner is the sole sexual partner for the female subject and is sterilized prior to the subject's entry into the study)
• Intrauterine device with a failure rate of less than 1% per year
• Double barrier method (e.g., spermicide plus a condom or a diaphragm) Note: Women who have had a hysterectomy or tubal ligation are considered to be of non-childbearing potential. Since a pharmacokinetic interaction has been observed between LTG and estrogen-based oral contraceptives, the use of hormonal therapy such as for contraception or hormone replacement therapy is not allowed.
• Outpatients 6.Subjects who can keep a seizure diary 7.Subjects who can understand and sign the informed consent. If the subject is under 20 years old at the time of consent, both the subject and subject's legally acceptable representative have to sign the consent to participate in the study.
• QTc \<480 msec for subjects with bundle branch block or QTc \<450 msec for other subjects, in which QTc is measured by either single or triplicate-averaged ECG 9.Subjects who can comply with dosing of the investigational and standard products and all study procedures

You may not qualify if:

• Subjects with a history of hypersensitivity to LTG
• Subjects with a history of rash associated with other AED treatments.
• Subjects who have received another AED besides VPA during the 12 weeks prior to start of the investigational product
• Subjects with status epilepticus during the 6 months prior to start of the investigational product
• Subjects with a history of substance (including alcohol and drug) dependence or substance abuse as defined by the DSM-IV-TR within 12 months or 1 month, respectively, prior to start of the investigational product
• Subjects with a severe acute or chronic illness likely to impair drug absorption, distribution, metabolism, or excretion; or subjects with any unstable physical symptom likely to require hospitalization during the study
• Subjects with a severe psychiatric disorder that affects the procedures of the study or drug assessment
• Subjects with an acute or progressive neurological disorder or an organic disease
• Subjects with any clinically significant cardiac, renal, or hepatic medical condition. Any patient with these conditions will be excluded from the study even if these conditions are being controlled with a chronic therapy.
• Subjects who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study
• Subjects who are suspected to have an urea cycle disorder as below:
• Subjects with a history of encephalopathy or coma of unknown cause
• Subjects with a family history of infant death of unknown cause or urea cycle disorder
• Subjects taking inducers of LTG glucuronidation (i.e., rifampicinor lopinavir/ritonavir), atazanavir/ritonavir, risperidone, or oral contraceptives or hormone drugs containing estrogen
• Subjects taking carbapenem antibiotic (i.e., panipenem/betamipron, meropenem hydrate, imipenem hydrate/cilastatin sodium, biapenem, doripenem hydrate, or tebipenem pivoxil)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (7)

GSK Investigational Site

Hyōgo, 664-8540, Japan

Location

GSK Investigational Site

Kagoshima, 892-0844, Japan

Location

GSK Investigational Site

Kyoto, 606-8507, Japan

Location

GSK Investigational Site

Osaka, 560-8565, Japan

Location

GSK Investigational Site

Saitama, 351-8551, Japan

Location

GSK Investigational Site

Shizuoka, 430-8558, Japan

Location

GSK Investigational Site

Tokyo, 185-0012, Japan

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Epilepsy

Interventions

Lamotrigine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2014
• First Posted: April 1, 2014
• Study Start: April 12, 2014
• Primary Completion: May 11, 2015
• Study Completion: May 11, 2015
• Last Updated: November 17, 2017
• Results First Posted: February 1, 2016

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

JP (7)