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Completed

NCT Number: NCT03695094

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

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.

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Key information

Conditions

Epilepsy Brain Diseases Central Nervous System Diseases Nervous System Diseases

Age range

18 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Up0070 101, Sofia, Bulgaria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • 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
  • 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)

Treatment and study plan

Padsevonil

Drug

Padsevonil (PSL) will be dosed to steady state and the effect of background therapies on pharmacokinetics will be assessed

Other names: PSL, UCB0942

Oxcarbazepine

Drug

Concomitant administration of oxcarbazepine (OXC) at therapeutic dosage

Other names: OXC

Levetiracetam

Drug

Concomitant administration of levetiracetam (LEV) at therapeutic dosage

Other names: LEV

Lamotrigine

Drug

Concomitant administration of lamotrigine (LTG) at therapeutic dosage

Other names: LTG

Brivaracetam

Drug

Concomitant administration of brivaracetam (BRV) at therapeutic dosage

Other names: BRV

Primary outcomes

  1. The Maximum Observed Plasma Concentration (Cmax) of Padsevonil (PSL) During the Study

    Time frame: 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

    The Cmax for Padsevonil in plasma was expressed in nanograms per milliliter (ng/mL).

  2. The Time to Reach Maximum Concentration (Tmax) for Padsevonil During the Study

    Time frame: 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

    The tmax for Padsevonil in plasma was expressed in hours (hr).

  3. The Area Under the Plasma Concentration Time Curve (AUCtau) Over a Dosing Interval for PSL

    Time frame: 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

    The AUCtau for Padsevonil in plasma was expressed in hours times nanograms per milliliter (hr*ng/mL).

  4. The Apparent Total Plasma Clearance at Steady-state (CL/Fss) for PSL During the Study

    Time frame: 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

    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).

Secondary outcomes

  1. Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL

    Time frame: Trough plasma samples were taken prior to the morning dose of OXC on Day -1, Day 1 through Day 20 (+/-1)

    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).

  2. The Maximum Observed Plasma Concentration (Cmax) for UCB1431322-000 During the Study

    Time frame: 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

    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).

  3. The Time to Reach Maximum Concentration (Tmax) for UCB1431322-000 During the Study

    Time frame: 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

    The tmax for UCB1431322-000 in plasma was expressed in hours (hr).

  4. The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1431322-000 During the Study

    Time frame: 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

    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).

  5. The Ratio of PSL Metabolite UCB1431322-000 to PSL Based on the Area Under the Curve (AUCtau) During the Study

    Time frame: 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

    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).

  6. The Maximum Observed Plasma Concentration (Cmax) for UCB1447499-000 During the Study

    Time frame: 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

    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).

  7. The Time to Reach Maximum Concentration (Tmax) for UCB1447499-000 During the Study

    Time frame: 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

    The tmax for UCB1447499-000 in plasma was expressed in hr.

  8. The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1447499-000 During the Study

    Time frame: 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

    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).

  9. The Ratio of PSL Metabolite UCB1447499-000 to PSL Based on the Area Under the Curve (AUCtau)

    Time frame: 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

    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).

  10. Percentage of Participants With at Least One Adverse Event (AE) During the Study

    Time frame: From screening (Day -28 to Day -2) up to end of study (EOS) visit day 20 (+/-1)

    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.

  11. Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study

    Time frame: From screening (Day -28 to Day -2) up to end of study (EOS) visit day 20 (+/-1)

    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.

Sponsors and collaborators

Lead sponsor

UCB Biopharma S.P.R.L.

Industry

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Oct 3, 2018
Registry last updated
Jun 4, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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