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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-002797-31 | EudraCT Number |
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Based on available data, UCB has decided to stop development of padsevonil as adjunctive treatment of focal-onset seizures
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Placebo | Placebo Comparator | Study participants randomized to this arm will receive placebo twice daily to maintain the blinding. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Padsevonil | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 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 moxifloxacin 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 |
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Inclusion Criteria:
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| UCB Cares | 001 844 599 2273 (UCB) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Up0050 001 | London | United Kingdom |
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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The Participant Flow refers to the Safety Set.
The study started to enroll study participants in October 2019 and concluded in May 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Sequence: ABC | Padsevonil (PSL) Treatment Period (Treatment A)- participants received PSL 100 milligrams (mg) to 400 mg, orally twice daily (bid) during the 11 Days PSL Treatment Period. On Day 8, the Target Dose Day, participants received PSL 400 mg in the morning only and placebo in the afternoon. Placebo Treatment Period (Treatment B)-participants received Placebo matched to PSL Treatment Period doses, bid up to Day 11. Moxifloxacin (MXF) Treatment Period (Treatment C)- participants received placebo matched to PSL Treatment Period doses, bid up to Day 11. On Day 8, the Target Dose Day, participants received MXF 400 mg in the morning and placebo in the afternoon. Participants received PSL, Placebo, and MXF treatments at the first, the second and the third treatment periods respectively, with a minimum 7-day washout period between each treatment periods. |
| FG001 | Treatment Sequence: ACB | Participants received PSL, MXF, and Placebo treatments at the first, the second and the third treatment periods respectively, with a minimum 7-day washout period between each treatment periods. |
| FG002 | Treatment Sequence: BAC | Participants received Placebo, PSL, and MXF treatments at the first, the second and the third treatment periods respectively, with a minimum 7-day washout period between each treatment periods. |
| FG003 | Treatment Sequence: BCA | Participants received Placebo, MXF, and PSL treatments at the first, the second and the third treatment periods respectively, with a minimum 7-day washout period between each treatment periods. |
| FG004 | Treatment Sequence: CAB | Participants received MXF, PSL, and Placebo treatments at the first, the second and the third treatment periods respectively, with a minimum 7-day washout period between each treatment periods. |
| FG005 | Treatment Sequence: CBA | Participants received MXF, Placebo, and PSL treatments at the first, the second and the third treatment periods respectively, with a minimum 7-day washout period between each treatment periods. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Baseline Characteristics refer to the Safety Set which consisted of all study participants who received at least 1 dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment Sequence: ABC | Padsevonil (PSL) Treatment Period (Treatment A) participants received PSL 100 milligrams (mg) to 400 mg, orally twice daily (bid) during the 11 Days PSL Treatment Period. On Day 8, the Target Dose Day, participants received PSL 400 mg in the morning only and placebo in the afternoon. Placebo Treatment Period (Treatment B) participants received Placebo matched to PSL Treatment Period doses, bid up to Day 11. Moxifloxacin (MXF) Treatment Period (Treatment C) participants received placebo matched to PSL Treatment Period doses, bid up to Day 11. On Day 8, the Target Dose Day, participants received MXF 400 mg in the morning and placebo in the afternoon. Participants received PSL, Placebo, and MXF treatments at the first, the second and the third treatment periods respectively, with a minimum 7-day washout period between each treatment periods. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The QT/QTc Set included all study participants in the SS with measurements at Baseline as well as on-treatment with at least 1 postdose time point with a valid change-from Baseline QTcF (ΔQTcF) value. Here, number of participants were included who were evaluable for the assessment. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds (ms) | 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 |
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From Baseline to Safety Follow Up (up to Day 67)
Any AE that starts on or after the date of the first dose of study drug and on or before the last date of the last treatment period or any unresolved event already present before administration of treatment that worsens in intensity following exposure to the treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Padsevonil (SS) | Participants received PSL 100 mg to 400 mg orally bid during the 11 Days PSL Treatment Period. On Day 8, the Target Dose Day, participants received PSL 400 mg in the morning only and placebo in the afternoon. Participants formed Safety Set (SS). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diplopia | Eye disorders | MedDRA22.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| UCB | Cares | +1844 599 | 2273 | UCBCares@ucb.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 10, 2019 | May 10, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 22, 2020 | May 10, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000708857 | padsevonil |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
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| Moxifloxacin | Drug |
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| Placebo | Drug |
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| Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Placebo-corrected change from Baseline in HR, (ΔΔHR) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | 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 | Placebo-corrected change from Baseline in HR, (ΔΔHR) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | 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 | Placebo-corrected change from Baseline in PR, (ΔΔPR) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | 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 | Placebo-corrected change from Baseline in PR, (ΔΔPR) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | 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 QRS Interval on Day 1 | Placebo-corrected change from Baseline for QRS interval, (ΔΔQRS) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | 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 QRS Interval on Day 8 | Placebo-corrected change from Baseline for QRS interval, (ΔΔQRS) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | 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 |
| Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Number of Participants with treatment-emergent changes of electrocardiogram waveforms as T-waves and U-waves. If a given morphology occurs multiple times at a given time point, that occurrence was only counted 1 time for that time point. If more than 1 morphology type was observed at a given time point, both morphology types were counted. A subject can appear in more than 1 category. | 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 |
| Change From Baseline in QTcF Evaluated at Drug-specific Tmax for Padsevonil | Change from Baseline in QTcF (ΔQTcF) evaluated at drug-specific tmax (Δtmax) for padsevonil, using an analysis of variance (ANOVA) mixed-effect model. | 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 |
| Change From Baseline in QTcF Evaluated at Drug-specific Tmax for Metabolite 1 | Change from Baseline in QTcF (ΔQTcF) evaluated at drug-specific tmax (Δtmax) for metabolite 1, using an analysis of variance (ANOVA) mixed-effect model. | 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 |
| Change From Baseline in QTcF Evaluated at Drug-Specific Tmax for Metabolite 2 | Change from Baseline in QTcF (ΔQTcF) evaluated at drug-specific tmax (Δtmax) for metabolite 2, using an analysis of variance (ANOVA) mixed-effect model. | 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 |
| Maximum Observed Plasma Concentration at Steady State (Cmax, ss) for Padsevonil | Cmax,ss: Maximum observed plasma concentration of padsevonil at steady state. | Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose |
| Time of Observed Maximum Concentration (Tmax) at Steady State for Padsevonil | tmax: Time of observed maximum plasma concentration at steady state. | Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose |
| Area Under the Plasma Concentration Time Curve (AUCtau) at Steady State for Padsevonil | AUCtau: Area under the plasma concentration time curve over a dosing interval at steady state. | Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose |
| Percentage of Participants With Adverse Events 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. | From Baseline to Safety Follow-up (up to Day 67) |
| Percentage of Participants With Serious Adverse Events From Baseline to Safety Follow-up (up to Day 67) | A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:
| From Baseline to Safety Follow-up (up to Day 67) |
| Percentage of Participants With Treatment Related Adverse Events 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. | From Baseline to Safety Follow-up (up to Day 67) |
| Percentage of Participants With Adverse Events Leading to Discontinuation of the Study 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. | From Baseline to Safety Follow-up (up to Day 67) |
| Withdrawal by Subject |
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| Related to COVID-19 pandemic |
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| BG001 | Treatment Sequence: ACB | Participants received PSL, MXF, and Placebo treatments at the first, the second and the third treatment periods respectively, with a minimum 7-day washout period between each treatment periods. |
| BG002 | Treatment Sequence: BAC | Participants received Placebo, PSL, and MXF treatments at the first, the second and the third treatment periods respectively, with a minimum 7-day washout period between each treatment periods. |
| BG003 | Treatment Sequence: BCA | Participants received Placebo, MXF, and PSL treatments at the first, the second and the third treatment periods respectively, with a minimum 7-day washout period between each treatment periods. |
| BG004 | Treatment Sequence: CAB | Participants received MXF, PSL, and Placebo treatments at the first, the second and the third treatment periods respectively, with a minimum 7-day washout period between each treatment periods. |
| BG005 | Treatment Sequence: CBA | Participants received MXF, Placebo, and PSL treatments at the first, the second and the third treatment periods respectively, with a minimum 7-day washout period between each treatment periods. |
| BG006 | Total Title |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Secondary | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 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 moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | The QT/QTc Set included all study participants in the SS with measurements at Baseline as well as on-treatment with at least 1 postdose time point with a valid change-from Baseline QTcF (ΔQTcF) value. Here, number of participants were included who were evaluable for the assessment. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds | 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 |
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| Secondary | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Placebo-corrected change from Baseline in HR, (ΔΔHR) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | The QT/QTc Set included all study participants in the SS with measurements at Baseline as well as on-treatment with at least 1 postdose time point with a valid change-from Baseline QTcF (ΔQTcF) value. Here, number of participants were included who were evaluable for the assessment. The Target Dose for moxifloxacin was at Day 8. Therefore, the data was analyzed at Day 8 only. | Posted | Least Squares Mean | 90% Confidence Interval | beats per minute (bpm) | Day 1 : 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose |
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| Secondary | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Placebo-corrected change from Baseline in HR, (ΔΔHR) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | The QT/QTc Set included all study participants in the SS with measurements at Baseline as well as on-treatment with at least 1 postdose time point with a valid change-from Baseline QTcF (ΔQTcF) value. Here, number of participants were included who were evaluable for the assessment. | Posted | Least Squares Mean | 90% Confidence Interval | beats per minute (bpm) | 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 |
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| Secondary | Placebo-corrected Change From Baseline for PR Interval on Day 1 | Placebo-corrected change from Baseline in PR, (ΔΔPR) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | The QT/QTc Set included all study participants in the SS with measurements at Baseline as well as on-treatment with at least 1 postdose time point with a valid change-from Baseline QTcF (ΔQTcF) value. Here, number of participants were included who were evaluable for the assessment. The Target Dose for moxifloxacin was at Day 8. Therefore, the data was analyzed at Day 8 only. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds | Day 1 : 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose |
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| Secondary | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Placebo-corrected change from Baseline in PR, (ΔΔPR) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | The QT/QTc Set included all study participants in the SS with measurements at Baseline as well as on-treatment with at least 1 postdose time point with a valid change-from Baseline QTcF (ΔQTcF) value. Here, number of participants were included who were evaluable for the assessment. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds | 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 |
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| Secondary | Placebo-corrected Change From Baseline for QRS Interval on Day 1 | Placebo-corrected change from Baseline for QRS interval, (ΔΔQRS) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | The QT/QTc Set included all study participants in the SS with measurements at Baseline as well as on-treatment with at least 1 postdose time point with a valid change-from Baseline QTcF (ΔQTcF) value. Here, number of participants were included who were evaluable for the assessment. The Target Dose for moxifloxacin was at Day 8. Therefore, the data was analyzed at Day 8 only. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds | Day 1 : 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose |
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| Secondary | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Placebo-corrected change from Baseline for QRS interval, (ΔΔQRS) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. | The QT/QTc Set included all study participants in the SS with measurements at Baseline as well as on-treatment with at least 1 postdose time point with a valid change-from Baseline QTcF (ΔQTcF) value. Here, number of participants were included who were evaluable for the assessment. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds | 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 |
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| Secondary | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Number of Participants with treatment-emergent changes of electrocardiogram waveforms as T-waves and U-waves. If a given morphology occurs multiple times at a given time point, that occurrence was only counted 1 time for that time point. If more than 1 morphology type was observed at a given time point, both morphology types were counted. A subject can appear in more than 1 category. | The QT/QTc Set included all study participants in the SS with measurements at Baseline as well as on-treatment with at least 1 postdose time point with a valid change-from Baseline QTcF (ΔQTcF) value. Here, number of participants were included who were evaluable for the assessment. | Posted | Count of Participants | Participants | 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 |
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| Secondary | Change From Baseline in QTcF Evaluated at Drug-specific Tmax for Padsevonil | Change from Baseline in QTcF (ΔQTcF) evaluated at drug-specific tmax (Δtmax) for padsevonil, using an analysis of variance (ANOVA) mixed-effect model. | The QT/QTc Set included all study participants in the SS with measurements at Baseline as well as on-treatment with at least 1 postdose time point with a valid change-from Baseline QTcF (ΔQTcF) value. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds | 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 |
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| Secondary | Change From Baseline in QTcF Evaluated at Drug-specific Tmax for Metabolite 1 | Change from Baseline in QTcF (ΔQTcF) evaluated at drug-specific tmax (Δtmax) for metabolite 1, using an analysis of variance (ANOVA) mixed-effect model. | The QT/QTc Set included all study participants in the SS with measurements at Baseline as well as on-treatment with at least 1 postdose time point with a valid change-from Baseline QTcF (ΔQTcF) value. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds | 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 |
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| Secondary | Change From Baseline in QTcF Evaluated at Drug-Specific Tmax for Metabolite 2 | Change from Baseline in QTcF (ΔQTcF) evaluated at drug-specific tmax (Δtmax) for metabolite 2, using an analysis of variance (ANOVA) mixed-effect model. | The QT/QTc Set included all study participants in the SS with measurements at Baseline as well as on-treatment with at least 1 postdose time point with a valid change-from Baseline QTcF (ΔQTcF) value. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds | 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 |
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| Secondary | Maximum Observed Plasma Concentration at Steady State (Cmax, ss) for Padsevonil | Cmax,ss: Maximum observed plasma concentration of padsevonil at steady state. | The PKS included all study participants who received at least 1 dose of study medication, had no important Protocol deviations affecting the PK, and for whom at least 1 measurable PK concentration was available. Here, number of participants were included who were evaluable for the assessment. | Posted | Geometric Mean | 95% Confidence Interval | nanogram per milliliter (ng/ml) | Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose |
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| Secondary | Time of Observed Maximum Concentration (Tmax) at Steady State for Padsevonil | tmax: Time of observed maximum plasma concentration at steady state. | The PKS included all study participants who received at least 1 dose of study medication, had no important Protocol deviations affecting the PK, and for whom at least 1 measurable PK concentration was available. Here, number of participants were included who were evaluable for the assessment. | Posted | Median | Full Range | hours (h) | Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose |
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| Secondary | Area Under the Plasma Concentration Time Curve (AUCtau) at Steady State for Padsevonil | AUCtau: Area under the plasma concentration time curve over a dosing interval at steady state. | The PKS included all study participants who received at least 1 dose of study medication, had no important Protocol deviations affecting the PK, and for whom at least 1 measurable PK concentration was available. Here, number of participants were included who were evaluable for the assessment. | Posted | Geometric Mean | 95% Confidence Interval | hour*nanogram per milliliter (h*ng/mL) | Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose |
|
|
|
| Secondary | Percentage of Participants With Adverse Events 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. | Safety Set included all participants who received at least 1 dose of study medication. | Posted | Number | percentage of participants | From Baseline to Safety Follow-up (up to Day 67) |
|
|
|
| Secondary | Percentage of Participants With Serious Adverse Events From Baseline to Safety Follow-up (up to Day 67) | A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:
| Safety Set included all participants who received at least 1 dose of study medication. | Posted | Number | percentage of participants | From Baseline to Safety Follow-up (up to Day 67) |
|
|
|
| Secondary | Percentage of Participants With Treatment Related Adverse Events 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. | Safety Set included all participants who received at least 1 dose of study medication. | Posted | Number | percentage of participants | From Baseline to Safety Follow-up (up to Day 67) |
|
|
|
| Secondary | Percentage of Participants With Adverse Events Leading to Discontinuation of the Study 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. | Safety Set included all participants who received at least 1 dose of study medication. | Posted | Number | percentage of participants | From Baseline to Safety Follow-up (up to Day 67) |
|
|
|
| 0 |
| 51 |
| 0 |
| 51 |
| 38 |
| 51 |
| EG001 | Moxifloxacin (SS) | Participants received placebo matched to PSL Treatment Period doses, bid up to Day 11. On Day 8, the Target Dose Day, participants received MXF 400 mg in the morning and placebo in the afternoon. Participants formed the SS. | 0 | 51 | 0 | 51 | 13 | 51 |
| EG002 | Placebo (SS) | Participants received placebo matched to PSL Treatment Period doses, bid up to Day 11. Participants formed the SS. | 0 | 50 | 0 | 50 | 7 | 50 |
| Nausea | Gastrointestinal disorders | MedDRA22.1 | Non-systematic Assessment |
|
| Medical device site reaction | General disorders | MedDRA22.1 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA22.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA22.1 | Non-systematic Assessment |
|
| Sedation | Nervous system disorders | MedDRA22.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA22.1 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA22.1 | Non-systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA22.1 | Non-systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | MedDRA22.1 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA22.1 | Non-systematic Assessment |
|
| Irritability | Psychiatric disorders | MedDRA22.1 | Non-systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA22.1 | Non-systematic Assessment |
|
Not provided
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| Title | Measurements |
|---|---|
|
| 0.25 hour Postdose |
|
| 0.5 hour Postdose |
|
| 1 hour Postdose |
|
| 1.5 hours Postdose |
|
| 2 hours Postdose |
|
| 3 hours Postdose |
|
| 4 hours Postdose |
|
| 6 hours Postdose |
|
| 8 hours Postdose |
|
| 12 hours Postdose |
|
| 18 hours Postdose |
|
| 24 hours Postdose |
|
|
| Day 1: 1.5 hours Postdose |
|
| Day 1: 2 hours Postdose |
|
| Day 1: 3 hours Postdose |
|
| Day 1: 4 hours Postdose |
|
| Day 1: 6 hours Postdose |
|
| Day 1: 8 hours Postdose |
|
| Day 1: 12 hours Postdose |
|
| Day 1: 24 hours Postdose |
|
| Day 8: 0.25 hour Predose |
|
| Day 8: 0.25 hour Postdose |
|
| Day 8: 0.5 hour Postdose |
|
| Day 8: 1 hour Postdose |
|
| Day 8: 1.5 hours Postdose |
|
| Day 8: 2 hours Postdose |
|
| Day 8: 3 hours Postdose |
|
| Day 8: 4 hours Postdose |
|
| Day 8: 6 hours Postdose |
|
| Day 8: 8 hours Postdose |
|
| Day 8: 12 hours Postdose |
|
| Day 8: 18 hours Postdose |
|
| Day 8: 24 hours Postdose |
|
|
| Day 1: 1.5 hours Postdose |
|
| Day 1: 2 hours Postdose |
|
| Day 1: 3 hours Postdose |
|
| Day 1: 4 hours Postdose |
|
| Day 1: 6 hours Postdose |
|
| Day 1: 8 hours Postdose |
|
| Day 1: 12 hours Postdose |
|
| Day 1: 24 hours Postdose |
|
| Day 8: 0.25 hour Predose |
|
| Day 8: 0.25 hour Postdose |
|
| Day 8: 0.5 hour Postdose |
|
| Day 8: 1 hour Postdose |
|
| Day 8: 1.5 hours Postdose |
|
| Day 8: 2 hours Postdose |
|
| Day 8: 3 hours Postdose |
|
| Day 8: 4 hours Postdose |
|
| Day 8: 6 hours Postdose |
|
| Day 8: 8 hours Postdose |
|
| Day 8: 12 hours Postdose |
|
| Day 8: 18 hours Postdose |
|
| Day 8: 24 hours Postdose |
|
|
| Day 1: 1.5 hours Postdose |
|
| Day 1: 2 hours Postdose |
|
| Day1: 3 hours Postdose |
|
| Day 1: 4 hours Postdose |
|
| Day1: 6 hours Postdose |
|
| Day1: 8 hours Postdose |
|
| Day1: 12 hours Postdose |
|
| Day1: 24 hours Postdose |
|
| Day 8: 0.25 hour Predose |
|
| Day 8: 0.25 hour Postdose |
|
| Day 8: 0.5 hour Postdose |
|
| Day 8: 1 hour Postdose |
|
| Day 8: 1.5 hours Postdose |
|
| Day 8: 2 hours Postdose |
|
| Day 8: 3 hours Postdose |
|
| Day 8: 4 hours Postdose |
|
| Day 8: 6 hours Postdose |
|
| Day 8: 8 hours Postdose |
|
| Day 8: 12 hours Postdose |
|
| Day 8: 18 hours Postdose |
|
| Day 8: 24 hours Postdose |
|
| Title | Measurements |
|---|---|
|
| Biphasic |
|
| Normal (-) |
|
| Notched (-) |
|
| U-Wave Presence |
|