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

NCT04126343 | Terminated Phase 1 Results

• 2 other identifiers: UP00502019-002797-31
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Study Participants

Keywords

Healthy study participants; Padsevonil; Moxifloxacin; Cardiac repolarization

Outcome Measures

Primary Outcomes (1)

• Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil

  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 linear mixed-effects model analysis.

  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 (18)

• Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8

  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

• Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1

  Day 1 : 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8

  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

• Placebo-corrected Change From Baseline for PR Interval on Day 1

  Day 1 : 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• Placebo-corrected Change From Baseline for PR Interval on Day 8

  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

Study Arms (3)

Padsevonil

EXPERIMENTAL

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; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Study participants randomized to this arm will receive placebo twice daily to maintain the blinding.

Drug: Placebo

Moxifloxacin

ACTIVE COMPARATOR

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; Drug: Placebo

Interventions

Padsevonil DRUG

* 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

Padsevonil

Moxifloxacin DRUG

* Pharmaceutical form: Film-coated tablet * Route of administration: Oral use * Study participants will receive moxifloxacin once during the Treatment Period

Moxifloxacin

Placebo DRUG

* 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

Moxifloxacin; Padsevonil; Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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:
• QT interval corrected for heart rate using the Fridericia method (QTcF) ≥450 ms (on mean of triplicate ECG recordings);
• Other conduction abnormalities (defined as PR interval \>220 ms);
• QRS interval \>109 ms;
• Any rhythm other than sinus rhythm;
• Any history of Wolff-Parkinson-White Syndrome, Brugada Syndrome, unexplained syncope, or ventricular tachycardia;
• 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

Sponsors & Collaborators

• UCB Biopharma S.P.R.L.: lead

Study Sites (1)

Up0050 001

London, United Kingdom

Location

MeSH Terms

Interventions

padsevonil; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

+1844 599

Study Officials

• UCB Cares

  001 844 599 2273 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2019
• First Posted: October 15, 2019
• Study Start: October 23, 2019
• Primary Completion: May 22, 2020
• Study Completion: May 22, 2020
• Last Updated: June 18, 2021
• Results First Posted: June 18, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)