A Study in Participants With Epilepsy, to Evaluate the Pharmacokinetics, Safety and Tolerability of Oxcarbazepine on Padsevonil

Epilepsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03695094
• Other study ID #: UP0070
• Secondary ID: 2018-001941-16
• Status: Completed
• Phase: Phase 1
• Start date: September 18, 2018
• Est. completion date: May 30, 2019

Study information

• Verified date: May 2020
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the effect of stable coadministered oxcarbazepine (OXC), on the pharmacokinetics (PK), safety, tolerability of padsevonil (PSL) and the plasma PK of PSL metabolites, UCB1431322-000 and UCB1447499-000, in study participants with epilepsy compared with study participants co-medicated with stable doses of levetiracetam (LEV), lamotrigine (LTG) or brivaracetam (BRV) therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: May 30, 2019
• Est. primary completion date: May 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• 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

• Study participant is currently treated for epilepsy with stable doses of the following for at least 3 months:

1. Inducers Group: Oxcarbazepine (OXC) (at least 1200 mg/day as monotherapy or in combination with brivaracetam (BRV) [up to 200 mg/day], levetiracetam (LEV) [at least 1 g/day] or lamotrigine (LTG) [at least 150 mg/day]); or

2. Neutral (control) Group: LTG (at least 150 mg/day monotherapy or adjunctive to LEV or BRV), LEV (at least 1 g/day monotherapy or adjunctive to LTG), or BRV (up to 200 mg/day adjunctive to LTG)

• Study participant in the Inducers Group is taking OXC and has a trough OXC metabolite Mono Hydroxy Derivate (MHD) plasma level in the target range (=12.0 to =35.0 mcg/mL)

• 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

• Study participant has a body mass index (BMI) of 18 to 35 kg/m², inclusive, with a body weight of at least 50 kg (male) or 45 kg (female)

• 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). -Male study participant agrees that, during the study period, when having sexual intercourse with a woman of childbearing potential, he will use an efficient barrier contraceptive (condom plus spermicide) AND that the respective partner will use an additional efficient contraceptive method (eg, oral pills, intrauterine device, intrauterine hormone-releasing systems, or diaphragm, and spermicide)

Exclusion Criteria:

• 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)

• Study participant has a known hypersensitivity to any components of the IMP as stated in this protocol

• 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

• Study participant has a history of status epilepticus during the last year

• Study participant has any clinically relevant electrocardiogram (ECG) finding at the Screening Visit or at Baseline

• Study participant has received any prescription or nonprescription medicines, including enzyme inhibitors or inducers, over the counter (OTC) remedies, herbal and dietary supplements (including St. John's Wort), or vitamins up to 2 weeks or 5 half-lives of the respective drug (whichever is longer) before the first administration of IMP and during the clinical part of the study, unless required to treat an Adverse event (AE). This does not include allowed antiepileptic drugs (AEDs) per the protocol, oral contraceptives not exceeding 30 µg ethinyl estradiol or postmenopausal hormone replacement therapy or implants, patches, or IUDs/IUSs delivering progesterone (for female study participants)

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• Padsevonil
Padsevonil (PSL) will be dosed to steady state and the effect of background therapies on pharmacokinetics will be assessed
• Oxcarbazepine
Concomitant administration of oxcarbazepine (OXC) at therapeutic dosage
• Levetiracetam
Concomitant administration of levetiracetam (LEV) at therapeutic dosage
• Lamotrigine
Concomitant administration of lamotrigine (LTG) at therapeutic dosage
• Brivaracetam
Concomitant administration of brivaracetam (BRV) at therapeutic dosage

Locations

Country	Name	City	State
Bulgaria	Up0070 101	Sofia
Netherlands	Up0070 401	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma S.P.R.L.

Countries where clinical trial is conducted

Bulgaria,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Maximum Observed Plasma Concentration (Cmax) of Padsevonil (PSL) During the Study	The Cmax for Padsevonil in plasma was expressed in nanograms per milliliter (ng/mL).	Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Primary	The Time to Reach Maximum Concentration (Tmax) for Padsevonil During the Study	The tmax for Padsevonil in plasma was expressed in hours (hr).	Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Primary	The Area Under the Plasma Concentration Time Curve (AUCtau) Over a Dosing Interval for PSL	The AUCtau for Padsevonil in plasma was expressed in hours times nanograms per milliliter (hr*ng/mL).	Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Primary	The Apparent Total Plasma Clearance at Steady-state (CL/Fss) for PSL During the Study	The CL/Fss for Padsevonil in plasma was expressed in liters per hour (L/hr). Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).	Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Secondary	Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL	The trough plasma concentration of MHD with PSL was expressed in micrograms per milliliter (µg/mL).; Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).	Trough plasma samples were taken prior to the morning dose of OXC on Day -1, Day 1 through Day 20 (+/-1)
Secondary	The Maximum Observed Plasma Concentration (Cmax) for UCB1431322-000 During the Study	The Cmax for UCB1431322-000 in plasma was expressed in nanograms per milliliter (ng/mL).; Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).	Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Secondary	The Time to Reach Maximum Concentration (Tmax) for UCB1431322-000 During the Study	The tmax for UCB1431322-000 in plasma was expressed in hours (hr).	Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Secondary	The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1431322-000 During the Study	The AUCtau for UCB1431322-000 in plasma in was expressed in hours times nanograms per milliliter (hr*ng/mL).; Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).	Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Secondary	The Ratio of PSL Metabolite UCB1431322-000 to PSL Based on the Area Under the Curve (AUCtau) During the Study	Metabolite-to-Parent Ratios were corrected for differences in molecular weight. Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).	Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Secondary	The Maximum Observed Plasma Concentration (Cmax) for UCB1447499-000 During the Study	The Cmax for UCB1447499-000 in plasma was expressed in ng/mL. Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).	Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Secondary	The Time to Reach Maximum Concentration (Tmax) for UCB1447499-000 During the Study	The tmax for UCB1447499-000 in plasma was expressed in hr.	Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Secondary	The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1447499-000 During the Study	The AUCtau for UCB1447499-000 in plasma was expressed in hr*ng/mL. Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).	Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Secondary	The Ratio of PSL Metabolite UCB1447499-000 to PSL Based on the Area Under the Curve (AUCtau)	Metabolite-to-Parent Ratios were corrected for differences in molecular weight. Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).	Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Secondary	Percentage of Participants With at Least One Adverse Event (AE) During the Study	An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	From screening (Day -28 to Day -2) up to end of study (EOS) visit day 20 (+/-1)
Secondary	Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study	A SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in patient hospitalization or prolongation of existing hospitalization, was a congenital anomaly or birth defect, was an infection that requires treatment parenteral antibiotics or other important medical events which based on medical or scientific judgement could jeopardize the patients, or could require medical or surgical intervention to prevent any of the above.	From screening (Day -28 to Day -2) up to end of study (EOS) visit day 20 (+/-1)