Multicentre, open-label, uncontrolled design to clinically evaluate whether the VPA dose could be reduced by additional treatment with LTG in Japanese female patients with epilepsy whose seizures were well controlled with VPA monotherapy.

Phase 1

• Conditions: Partial seizures (including secondary generalized seizures) or tonic-clonic seizures with or without myoclonus but without other generalized seizure type(s); MedDRA version: 20.0Level: LLTClassification code 10043999Term: Tonic-clonic epilepsySystem Organ Class: 100000038485; MedDRA version: 20.0Level: LLTClassification code 10065336Term: Partial epilepsySystem Organ Class: 100000014703; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2017-001515-36-Outside-EU/EEA
• Lead Sponsor: GlaxoSmithKline K.K.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-08-11
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: A
• Sex: Female
• Target Recruitment: 33

Inclusion Criteria

1.(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)
2.Subjects having a confident diagnosis of epilepsy that is uncomplicated by pseudoseizures such as psychogenic nonepileptic seizures
3.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)
4.(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:
1)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)
2)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.
5.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.
8.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

Are the trial subjects under 18? yes
Number of subjects for this age range: 33
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 27
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Subjects with a history of hypersensitivity to LTG
2.Subjects with a history of rash associated with other AED treatments.
3.Subjects who have received another AED besides VPA during the 12 weeks prior to start of the investigational product
4.Subjects with status epilepticus during the 6 months prior to start of the investigational product
5.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
6.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
7.Subjects with a severe psychiatric disorder that affects the procedures of the study or drug assessment
8.Subjects with an acute or progressive neurological disorder or an organic disease
9.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.
10.Subjects with an unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, or known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones)
Note: Chronic stable hepatitis B and C are acceptable if the subjects otherwise meet the inclusion criteria. However, the subjects with chronic stable hepatitis B will be excluded if significant immunosuppressive agents are being administered due to a risk of hepatitis B reactivation.
11.Subjects who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study
12.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
13.Subjects taking inducers of LTG glucuronidation (i.e., rifampicinor lopinavir/ritonavir), atazanavir/ritonavir, risperidone, or oral contraceptives or hormone drugs containing estrogen
14.Subjects taking carbapenem antibiotic (i.e., panipenem/betamipron, meropenem hydrate, imipenem hydrate/cilastatin sodium, biapenem, doripenem hydrate, or tebipenem pivoxil)
15.Subjects who have participated in other clinical studies within 3 months prior to start of the investigational product
16.Subjects who have had active suicidal plans/intent or suicidal thoughts in the past 3 months prior to start of the investigational product; or subjects who have history of suicide attempts in the last 1 year prior to start of the investigational product or of multiple suicide attempts in their lifetime
17.Subjects whom the investigator or subinvestigator considers ineligible for the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified