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A Study to Test the Cardiac Effects of Padsevonil in Healthy Study Participants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04126343
Recruitment Status : Suspended (Study temporarily halted as a precautionary measure due to the COVID-19 pandemic)
First Posted : October 15, 2019
Last Update Posted : May 21, 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 effects on cardiac repolarization of high-dose padsevonil (PSL) in comparison to placebo in healthy study participants.

Condition or disease Intervention/treatment Phase
Healthy Study Participants Drug: Padsevonil Drug: Moxifloxacin Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Single-Center, Randomized, Placebo-Controlled, 3 Treatment Period Crossover Study to Assess the Effect of Padsevonil on Cardiac Repolarization (QTc Interval) (Using Moxifloxacin as a Positive Control) in Healthy Study Participants
Actual Study Start Date : October 23, 2019
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Padsevonil
Study participants randomized to this arm will receive assigned doses of padsevonil twice daily. On Day 8 padsevonil will be administered in the morning, and placebo will administered in the evening.
Drug: Padsevonil
  • Pharmaceutical form: Film-coated tablet
  • Route of administration: Oral use
  • Study participants will receive padsevonil in a pre-specified dosing sequence during the Treatment Period

Drug: Placebo
  • Pharmaceutical form: Film-coated tablet
  • Route of administration: Oral use
  • Study participants will receive placebo in a pre-specified sequence during the Treatment Period to match padsevonil and maintain the blinding

Placebo Comparator: Placebo
Study participants randomized to this arm will receive placebo twice daily to maintain the blinding.
Drug: Placebo
  • Pharmaceutical form: Film-coated tablet
  • Route of administration: Oral use
  • Study participants will receive placebo in a pre-specified sequence during the Treatment Period to match padsevonil and maintain the blinding

Active Comparator: Moxifloxacin
Study participants randomized to this arm will receive padsevonil-placebo twice daily. On Day 8 placebo will be administered in the morning, and moxifloxacin will administered in the evening.
Drug: Moxifloxacin
  • Pharmaceutical form: Film-coated tablet
  • Route of administration: Oral use
  • Study participants will receive moxifloxacin once during the Treatment Period

Drug: Placebo
  • Pharmaceutical form: Film-coated tablet
  • Route of administration: Oral use
  • Study participants will receive placebo in a pre-specified sequence during the Treatment Period to match padsevonil and maintain the blinding




Primary Outcome Measures :
  1. Change from Baseline in QTcF [ Time Frame: On Day 1 and Day 8 in Treatment Periods 1, 2, and 3 ]
    Placebo-corrected change from Baseline in corrected QT interval (QTc), based on Fridericia's correction (QTcF) method (ΔΔQTcF) evaluated during the Target Dose Day of the padsevonil and placebo Treatment Periods, using time point analysis.


Secondary Outcome Measures :
  1. Change from Baseline in QTcF after a single dose of moxifloxacin [ Time Frame: On Day 1 and Day 8 in Treatment Periods 1, 2, or 3 ]
    Placebo-corrected change from Baseline in QTcF after a single dose of moxifloxacin

  2. Change from Baseline for heart rate (HR) interval [ Time Frame: On Day 1 and Day 8 in Treatment Periods 1, 2, and 3 ]
    Placebo-corrected change from Baseline for HR interval

  3. Change from Baseline for PR interval [ Time Frame: On Day 1 and Day 8 in Treatment Periods 1, 2, and 3 ]
    Placebo-corrected changes from Baseline for PR interval

  4. Change from Baseline for QRS interval [ Time Frame: On Day 1 and Day 8 in Treatment Periods 1, 2, and 3 ]
    Placebo-corrected changes from Baseline for QRS interval

  5. Frequency of treatment-emergent changes for T-wave morphology and U-wave presence [ Time Frame: On Day 1 and Day 8 in Treatment Periods 1, 2, and 3 ]
    Frequency of treatment-emergent changes of electrocardiogram waveforms as T-waves and U-waves.

  6. Change from Baseline in QTcF evaluated at drug-specific tmax for padsevonil [ Time Frame: On Day 1 and Day 8 in Treatment Periods 1, 2, or 3 ]
    Change from Baseline in QTcF (ΔQTcF) evaluated at drug-specific tmax (Δtmax) for padsevonil

  7. Change from Baseline in QTcF evaluated at drug-specific tmax for UCB1431322-000 [ Time Frame: On Day 1 and Day 8 in Treatment Periods 1, 2, or 3 ]
    Change from Baseline in QTcF (ΔQTcF) evaluated at drug-specific tmax (Δtmax) for UCB1431322-000

  8. Change from Baseline in QTcF evaluated at drug-specific tmax for UCB1447499-000 [ Time Frame: On Day 1 and Day 8 in Treatment Periods 1, 2, or 3 ]
    Change from Baseline in QTcF (ΔQTcF) evaluated at drug-specific tmax (Δtmax) for UCB1447499-000

  9. Cmax for padsevonil at steady state (Cmax,ss) [ Time Frame: On Day 8 in Treatment Periods 1, 2, or 3 ]
    Cmax,ss: Maximum observed plasma concentration of padsevonil at steady state

  10. tmax of padsevonil at steady state [ Time Frame: On Day 8 in Treatment Periods 1, 2, or 3 ]
    tmax: Time of observed maximum plasma concentration at steady state

  11. AUCtau of padsevonil at steady state [ Time Frame: On Day 8 in Treatment Periods 1, 2, or 3 ]
    AUCtau: Area under the plasma concentration time curve over a dosing interval at steady state

  12. Incidence of Adverse events [ Time Frame: From Screening to Safety Follow-up (up to Day 67) ]
    An Adverse Event is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage

  13. Incidence of Serious Adverse events [ Time Frame: From Screening to Safety Follow-up (up to Day 67) ]

    A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:

    • Results in death
    • Is life-threatening
    • Requires in patient hospitalization or prolongation of existing hospitalization
    • Is a congenital anomaly or birth defect
    • Is infection that requires treatment parenteral antibiotics
    • Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above

  14. Incidence of treatment related Adverse events [ Time Frame: From Baseline to Safety Follow-up (up to Day 67) ]
    An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

  15. Incidence of Adverse events leading to discontinuation of the study [ Time Frame: From Baseline to Safety Follow-up (up to Day 67) ]
    An Adverse Event is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. The results of this Primary Outcome Measure are summarized from the Adverse Event pages of the Case Report Forms.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent form (ICF)
  • Participant who is overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
  • Body weight of at least 50 kilogram (kg) (males) or 45 kg (females) and body mass index (BMI) within the range 18 to 30 kg/m2 (inclusive)
  • Male and/or female:

A male study participant must agree to use contraception during the Treatment Period and for at least 90 days after the last dose of study medication and refrain from donating sperm during this period

A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance during the Treatment Period and for at least 90 days after the last dose of study medication

Exclusion Criteria:

  • Participant has a known hypersensitivity to any components of the study medication or comparative drugs as stated in this protocol or history of tendon pathology secondary to use of quinolone antibiotics
  • Participant has a history of unexplained syncope or a family history of sudden death due to long QT syndrome
  • Participant has a present condition of respiratory or cardiovascular disorders, eg, cardiac insufficiency, coronary heart disease, hypertension, arrhythmia, tachyarrhythmia, or myocardial infarction
  • Past or intended use of over-the-counter (OTC) or prescription medication including herbal medications within 2 weeks or 5 half-lives prior to dosing.
  • Participant has used hepatic enzyme-inducing drugs (eg, glucocorticoids, phenobarbital, isoniazid, phenytoin, rifampicin, etc) within 2 months prior to the first dose of study medication
  • Participant has previously received padsevonil (PSL) in this or any other study
  • Participant has any clinically relevant electrocardiogram (ECG) finding at the Screening Visit or at Baseline. Participant has an abnormality in the 12-lead ECG that, in the opinion of the Investigator, increases the risks associated with participating in the study. In addition, any participant with any of the following findings will be excluded:

    1. QT interval corrected for heart rate using the Fridericia method (QTcF) ≥450 ms (on mean of triplicate ECG recordings);
    2. Other conduction abnormalities (defined as PR interval >220 ms);
    3. QRS interval >109 ms;
    4. Any rhythm other than sinus rhythm;
    5. Any history of Wolff-Parkinson-White Syndrome, Brugada Syndrome, unexplained syncope, or ventricular tachycardia;
    6. Family history of QTc prolongation or of unexplainable sudden death at <50 years of age
  • Participant has made a blood or plasma donation or has had a comparable blood loss (>450 mL) within 30 days prior to the Screening Visit. Blood donation during the study is not permitted

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): NCT04126343


Locations
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United Kingdom
Up0050 001
London, United Kingdom
Sponsors and Collaborators
UCB Biopharma S.P.R.L.
Investigators
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Study Director: UCB Cares 001 844 599 2273 (UCB)
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Responsible Party: UCB Biopharma S.P.R.L.
ClinicalTrials.gov Identifier: NCT04126343    
Other Study ID Numbers: UP0050
2019-002797-31 ( EudraCT Number )
First Posted: October 15, 2019    Key Record Dates
Last Update Posted: May 21, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Due to the small sample size in this trial, Individual Patient Data cannot be adequately anonymized and there is a reasonable likelihood that individual participants could be re-identified. For this reason, data from this trial cannot be shared.

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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. ):
Healthy study participants
Padsevonil
Moxifloxacin
Cardiac repolarization
Additional relevant MeSH terms:
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Moxifloxacin
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents