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

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ClinicalTrials.gov Identifier: NCT03695094
Recruitment Status : Completed
First Posted : October 3, 2018
Results First Posted : June 4, 2020
Last Update Posted : June 4, 2020
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Biopharma S.P.R.L. )

Brief 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.

Condition or disease Intervention/treatment Phase
Epilepsy Drug: Padsevonil Drug: Oxcarbazepine Drug: Levetiracetam Drug: Lamotrigine Drug: Brivaracetam Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : September 18, 2018
Actual Primary Completion Date : May 18, 2019
Actual Study Completion Date : May 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy

Arm Intervention/treatment
Experimental: Cohort 1
Cohort 1 (Inducers): Study participants on stable therapy with oxcarbazepine (OXC) either as monotherapy or adjunctive to levetiracetam (LEV), lamotrigine (LTG), or brivaracetam (BRV). OXC may be used as monotherapy or in combination with 1 or more of LEV, LTG, or BRV. Padsevonil (PSL) will be dosed to steady state and the effect of background therapy on PSL pharmacokinetics will be assessed at steady state.
Drug: Padsevonil
Padsevonil (PSL) will be dosed to steady state and the effect of background therapies on pharmacokinetics will be assessed
Other Names:
  • PSL
  • UCB0942

Drug: Oxcarbazepine
Concomitant administration of oxcarbazepine (OXC) at therapeutic dosage
Other Name: OXC

Drug: Levetiracetam
Concomitant administration of levetiracetam (LEV) at therapeutic dosage
Other Name: LEV

Drug: Lamotrigine
Concomitant administration of lamotrigine (LTG) at therapeutic dosage
Other Name: LTG

Drug: Brivaracetam
Concomitant administration of brivaracetam (BRV) at therapeutic dosage
Other Name: BRV

Experimental: Cohort 2
Cohort 2 (Neutral): Study participants on stable therapy with lamotrigine (LTG), levetiracetam (LEV), or brivaracetam (BRV). LTG or LEV may be used as monotherapy or in combination with each other. BRV may only be used in combination with LTG. LTG or LEV may be used as monotherapy or in combination with each other. BRV may only be used in combination with LTG. Padsevonil (PSL) will be dosed to steady state (4.5 days) and the effect of background therapy on PSL pharmacokinetics will be assessed at steady state.
Drug: Padsevonil
Padsevonil (PSL) will be dosed to steady state and the effect of background therapies on pharmacokinetics will be assessed
Other Names:
  • PSL
  • UCB0942

Drug: Levetiracetam
Concomitant administration of levetiracetam (LEV) at therapeutic dosage
Other Name: LEV

Drug: Lamotrigine
Concomitant administration of lamotrigine (LTG) at therapeutic dosage
Other Name: LTG

Drug: Brivaracetam
Concomitant administration of brivaracetam (BRV) at therapeutic dosage
Other Name: BRV




Primary Outcome Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03695094


Locations
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Bulgaria
Up0070 101
Sofia, Bulgaria
Netherlands
Up0070 401
Leiden, Netherlands
Sponsors and Collaborators
UCB Biopharma S.P.R.L.
Investigators
Layout table for investigator information
Study Director: UCB Cares 001 844 599 2273 (UCB)
  Study Documents (Full-Text)

Documents provided by UCB Pharma ( UCB Biopharma S.P.R.L. ):
Study Protocol  [PDF] June 8, 2018
Statistical Analysis Plan  [PDF] October 26, 2018

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Responsible Party: UCB Biopharma S.P.R.L.
ClinicalTrials.gov Identifier: NCT03695094    
Other Study ID Numbers: UP0070
2018-001941-16 ( EudraCT Number )
First Posted: October 3, 2018    Key Record Dates
Results First Posted: June 4, 2020
Last Update Posted: June 4, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UCB Pharma ( UCB Biopharma S.P.R.L. ):
Epilepsy
Phase 1
padsevonil
Additional relevant MeSH terms:
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Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lamotrigine
Oxcarbazepine
Levetiracetam
Brivaracetam
Anticonvulsants
Nootropic Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Sodium Channel Blockers
Voltage-Gated Sodium Channel Blockers
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers