A multicenter, open-label, parallel-group study in study participants with epilepsy to evaluate the effect of oxcarbazepine on the pharmacokinetics, safety, and tolerability of padsevonil.
- Conditions
- Epilepsyseizures10039911
- Registration Number
- NL-OMON46271
- Lead Sponsor
- CB Pharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
1. An Independent Ethics Committee (IEC) approved written ICF is signed and dated by the study participant.
2. Study participant is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, and medication intake according to the judgment of the Investigator.
3. Study participant is male or female between 18 to 64 years of age, inclusive, with a diagnosis of epilepsy according to the International League Against Epilepsy (ILAE) classification (Fisher et al, 2014).
4. Study participant is currently treated for epilepsy with stable doses of the following for at least 3 months:
a) Inducers Group: OXC (at least 1200mg/day as monotherapy or in combination with BRV [up to 200mg/day], LEV [at least 1g/day] or LTG [at least 150mg/day]); or
b) Neutral (control) Group: LTG (at least 150mg/day monotherapy or adjunctive to LEV or BRV), LEV (at least 1g/day monotherapy or adjunctive to LTG), or BRV (up to 200mg/day adjunctive to LTG).
5. Study participant in the Inducers Group is taking OXC and has a trough OXC metabolite (MHD) plasma level in the target range (*12.0 to *35.0 mcg/mL). At the Screening Visit, the blood sample must be collected no later than on Day -7 (with MHD reassessment, if required, no later than Day -4).
6. Study participant is in generally good physical and mental health, in the opinion of the Investigator, determined on the basis of medical history and a general clinical examination at the Screening Visit (ie, study participant has no current or past medical history of clinical significance, other than epilepsy, that would mitigate against their participation in the study).
7. Study participant has clinical laboratory test results within the local reference ranges or values are considered as not clinically relevant by the Investigator and approved by the UCB Study Physician. Laboratory parameters outside the reference ranges can be retested and if the retest result is within the reference range or considered as clinically not relevant the study participant is allowed in the study. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) should be within the normal limits. Liver enzymes up to 25% above the upper limit may be repeated once and should be within normal limits before inclusion.
8. Study participant has a body mass index (BMI) of 18 to 35kg/m², inclusive, with a body weight of at least 50kg (male) or 45kg (female).
9. Study participant has BP and PR within normal range in the supine position after 5 minutes rest (SBP: 90mmHg to 145mmHg, DBP: 40mmHg to 95mmHg, PR: 40bpm to 100bpm). Any values outside the normal range, but considered not clinically significant by the Investigator, are allowed.
10. Female study participant has a negative serum pregnancy test at the Screening Visit and agrees to use an efficient form of contraception for the duration of the study (unless menopausal [defined as no menses for 12 months without an alternative medical cause]; a high follicle-stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy). Hormonal contraception may be susceptible to an interaction with the IMP, which may reduce the efficacy of the contraception method. The potential for reduced efficacy of any hormonal contraception methods requires that a barrier met
Study participants are not permitted to enroll in the study if any of the following criteria is met:
1. Study participant has previously received the IMP administered in this study.
2. Study participant has participated in another study of an investigational medication (or a medical device) within the last 3 months before screening (or 5 half-lives, whichever is longer) or is currently participating in another study of an investigational medication (or a medical device).
3. Study participant has a known hypersensitivity to any components of the IMP as stated in this protocol
4. Study participant has a current or past psychiatric condition that, in the opinion of the Investigator, could compromise his/her safety or ability to participate in this study or a history of schizophrenia, or other psychotic disorder, bipolar disorder, or severe unipolar
depression. The presence of potential psychiatric exclusion criteria will be determined based on the psychiatric history collected at the Screening Visit.
5. Study participant has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has had suicidal ideation in the past 6 months as indicated by a positive response (*Yes*) to either Question 4 or Question 5 of the
*Screening/Baseline* version of the C-SSRS at the Baseline Visit.
6. Study participant has any medical condition that, in the opinion of the Investigator, could jeopardize or would compromise the study participant*s ability to participate in this study.
7. Study participant has a history of status epilepticus during the last year.
8. Study participant has a history or presence of drug or alcohol dependency or tests positive for alcohol and/or drugs at the Screening Visit or Day -1.
9. Study participant has a consumption of more than 3 units of alcohol/day in case of females, more than 4 units of alcohol/day in case of males.
10. Study participant smokes more than 5 cigarettes per day (or equivalent) or has done so within 6 months prior to the Screening Visit.
11. Study participant has a consumption of more than 600mg of caffeine/day within 7 days prior to the Baseline Visit and does not agree to limit consumption below this limit for the duration of the study (200mL of coffee contains approximately 100mg of caffeine, 200mL of black tea approximately 30mg, and 200mL of cola approximately 20mg).
12. Study participant ingests grapefruit, starfruit, or pawpaw (as beverage, fruit, or supplements) within 72 hours before first administration of IMP. These fruits are not allowed during the Treatment Period and throughout the study.
13. Study participant has either:
- >2.0x upper limit of normal (ULN) of any of the following:
* ALT
* AST
* ALP
-OR-
- ULN total bilirubin (*1.5xULN total bilirubin if known Gilbert*s syndrome).
If study participant has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert*s syndrome (ie, direct bilirubin <35%). For randomized study participant with a baseline result >ULN for ALT, AST, ALP, or total bilirubin, a baseline diagnosis and/or the cause of any clinically meaningful elevation must
be understood and recorded. If study participant has >ULN ALT, AST, or ALP that does not meet the exclusion limit at
screening, repeat the tests, if possible, prior to dosing to ensure there is no furth
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary pharmacokinetic variables will comprise Cmax, tmax, AUC*, and<br /><br>CL/Fss obtained from the plasma concentration-time profiles for PSL:<br /><br>- Cmax: maximum observed plasma concentration<br /><br>- tmax: time of maximum concentration<br /><br>- AUC*: area under the curve over a dosing interval (12 hours)<br /><br>- CL/Fss: apparent total clearance at steady-state</p><br>
- Secondary Outcome Measures
Name Time Method