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EpilepsyPhase 1NCT03695094

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

A Phase 1 study testing Padsevonil, Oxcarbazepine and Levetiracetam in people with Epilepsy, run by UCB Biopharma S.P.R.L. at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Epilepsy
What is being tested?
Padsevonil, Oxcarbazepine and Levetiracetam
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
2 sitesin 2 countries
Study dates
18 Sep 2018to 30 May 2019
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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)

Who cannot join

  • 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)

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Bulgaria1 site

  • Up0070 101

    Sofia

Other trials in Bulgaria

Netherlands1 site

  • Up0070 401

    Leiden

Other trials in Netherlands

About this study

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

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.

Conditions
Epilepsy
Being tested
Padsevonil, Oxcarbazepine, Levetiracetam, Lamotrigine, Brivaracetam
Keywords
Epilepsy, Phase 1, padsevonil
Medical subject headings
Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PadsevonilDrug

    Also called PSL, UCB0942

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

  • OxcarbazepineDrug

    Also called OXC

    Concomitant administration of oxcarbazepine (OXC) at therapeutic dosage

  • LevetiracetamDrug

    Also called LEV

    Concomitant administration of levetiracetam (LEV) at therapeutic dosage

  • LamotrigineDrug

    Also called LTG

    Concomitant administration of lamotrigine (LTG) at therapeutic dosage

  • BrivaracetamDrug

    Also called BRV

    Concomitant administration of brivaracetam (BRV) at therapeutic dosage

Study groups in NCT03695094
Study groupRoleWhat they receive
Cohort 1ExperimentalCohort 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.
Receives: Drug: Padsevonil; Drug: Oxcarbazepine; Drug: Levetiracetam; Drug: Lamotrigine; Drug: Brivaracetam
Cohort 2ExperimentalCohort 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.
Receives: Drug: Padsevonil; Drug: Levetiracetam; Drug: Lamotrigine; Drug: Brivaracetam

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 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

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

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

    Measured: 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

  3. 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).

    Measured: 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

  4. 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).

    Measured: 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 outcomes (11)

  1. 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).

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

  2. 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).

    Measured: 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

  3. 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).

    Measured: 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

  4. 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).

    Measured: 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

  5. 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).

    Measured: 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

  6. 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).

    Measured: 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

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

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

    Measured: 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

  8. 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).

    Measured: 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

  9. 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).

    Measured: 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

  10. 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.

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

  11. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Oct 2018
  2. Study start18 Sep 2018
  3. Primary completion18 May 2019
  4. Study completion30 May 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03695094
Sponsor's protocol ID
UP0070
Other IDs
2018-001941-16, 2018
Status last verified
May 2020
First submitted
14 Sep 2018
Last updated
4 Jun 2020
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chanteux H, MacPherson M, Kramer H, Otoul C, Okagaki T, Rospo C, De Bruyn S, Watling M, Bani M, Sciberras D. Overview of preclinical and clinical studies investigating pharmacokinetics and drug-drug interactions of padsevonil. Expert Opin Drug Metab Toxicol. 2024 Aug;20(8):841-855. doi: 10.1080/17425255.2024.2373108. Epub 2024 Jul 9.

    PubMed 38932723

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Padsevonil, Oxcarbazepine and Levetiracetam in people with Epilepsy, run by UCB Biopharma S.P.R.L. at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Bulgaria, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03695094, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2020.

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