Clinical trial NCT04126343: A Study to Test the Cardiac Effects of Padsevonil in Healthy Study Participants
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Study Participants
Keywords: Healthy study participants
Padsevonil
Moxifloxacin
Cardiac repolarization
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2019-10-15
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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

Primary outcomes:
measure: Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil
timeFrame: Day 8 : 0.75, 0.5, 0.25 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours postdose
Secondary outcomes:
measure: Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8
timeFrame: Day 8 : 0.75, 0.5, 0.25 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours postdose
measure: Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1
timeFrame: Day 1 : 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
measure: Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8
timeFrame: Day 8 : 0.75, 0.5, 0.25 predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours postdose
measure: Placebo-corrected Change From Baseline for PR Interval on Day 1
timeFrame: Day 1 : 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
measure: Placebo-corrected Change From Baseline for PR Interval on Day 8
timeFrame: Day 8 : 0.75, 0.5, 0.25 predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours postdose
measure: Placebo-corrected Change From Baseline for QRS Interval on Day 1
timeFrame: Day 1 : 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
measure: Placebo-corrected Change From Baseline for QRS Interval on Day 8
timeFrame: Day 8 : 0.75, 0.5, 0.25 predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours postdose
measure: Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence
timeFrame: Day 8 : 0.75, 0.5, 0.25 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours postdose
measure: Change From Baseline in QTcF Evaluated at Drug-specific Tmax for Padsevonil
timeFrame: Day 8 : 0.75, 0.5, 0.25 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose
measure: Change From Baseline in QTcF Evaluated at Drug-specific Tmax for Metabolite 1
timeFrame: Day 8 : 0.75, 0.5, 0.25 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose
measure: Change From Baseline in QTcF Evaluated at Drug-Specific Tmax for Metabolite 2
timeFrame: Day 8 : 0.75, 0.5, 0.25 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose
measure: Maximum Observed Plasma Concentration at Steady State (Cmax, ss) for Padsevonil
timeFrame: Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose
measure: Time of Observed Maximum Concentration (Tmax) at Steady State for Padsevonil
timeFrame: Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose
measure: Area Under the Plasma Concentration Time Curve (AUCtau) at Steady State for Padsevonil
timeFrame: Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose
measure: Percentage of Participants With Adverse Events From Baseline to Safety Follow-up (up to Day 67)
timeFrame: From Baseline to Safety Follow-up (up to Day 67)
measure: Percentage of Participants With Serious Adverse Events From Baseline to Safety Follow-up (up to Day 67)
timeFrame: From Baseline to Safety Follow-up (up to Day 67)
measure: Percentage of Participants With Treatment Related Adverse Events From Baseline to Safety Follow-up (up to Day 67)
timeFrame: From Baseline to Safety Follow-up (up to Day 67)
measure: Percentage of Participants With Adverse Events Leading to Discontinuation of the Study From Baseline to Safety Follow-up (up to Day 67)
timeFrame: From Baseline to Safety Follow-up (up to Day 67)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Up0050 001
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: