Healthy Study Participants
Conditions
Keywords
Healthy study participants, Padsevonil, Moxifloxacin, Cardiac repolarization
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.
Interventions
DRUGPadsevonil
* 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
DRUGMoxifloxacin
* Pharmaceutical form: Film-coated tablet * Route of administration: Oral use * Study participants will receive moxifloxacin once during the Treatment Period
DRUGPlacebo
* 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
Sponsors
UCB Biopharma S.P.R.L.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 HR, (ΔΔHR) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. |
| 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 in HR, (ΔΔHR) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. |
| 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 in PR, (ΔΔPR) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. |
| 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 | 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. |
| Placebo-corrected Change From Baseline for QRS 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 QRS interval, (ΔΔQRS) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. |
| Placebo-corrected Change From Baseline for QRS 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 QRS interval, (ΔΔQRS) evaluated during the Target Dose Day of the padsevonil/moxifloxacin and placebo Treatment Periods, using linear mixed-effects model analysis. |
| Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | 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 | 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. |
| Change From Baseline in QTcF Evaluated at Drug-specific Tmax for Padsevonil | 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 (ΔQTcF) evaluated at drug-specific tmax (Δtmax) for padsevonil, using an analysis of variance (ANOVA) mixed-effect model. |
| 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 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. |
| Change From Baseline in QTcF Evaluated at Drug-Specific Tmax for Metabolite 2 | 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 (ΔQTcF) evaluated at drug-specific tmax (Δtmax) for metabolite 2, using an analysis of variance (ANOVA) mixed-effect model. |
| Maximum Observed Plasma Concentration at Steady State (Cmax, ss) for Padsevonil | Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose | Cmax,ss: Maximum observed plasma concentration of padsevonil at steady state. |
| Time of Observed Maximum Concentration (Tmax) at Steady State for Padsevonil | Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose | tmax: Time of observed maximum plasma concentration at steady state. |
| Area Under the Plasma Concentration Time Curve (AUCtau) at Steady State for Padsevonil | Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose | AUCtau: Area under the plasma concentration time curve over a dosing interval at steady state. |
| Percentage of Participants With Adverse Events From Baseline to Safety Follow-up (up to Day 67) | 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. |
| Percentage of Participants With Serious Adverse Events From Baseline to Safety Follow-up (up to Day 67) | From Baseline 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. |
| Percentage of Participants With Treatment Related Adverse Events From Baseline to Safety Follow-up (up to Day 67) | 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. |
| Percentage of Participants With Adverse Events Leading to Discontinuation of the Study From Baseline to Safety Follow-up (up to Day 67) | 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. |
| Change From Baseline in QTcF Evaluated at Drug-specific Tmax for Metabolite 1 | 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 (ΔQTcF) evaluated at drug-specific tmax (Δtmax) for metabolite 1, using an analysis of variance (ANOVA) mixed-effect model. |
Countries
United Kingdom
Participant flow
Recruitment details
The study started to enroll study participants in October 2019 and concluded in May 2020.
Pre-assignment details
The Participant Flow refers to the Safety Set.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| 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. | 9 |
| 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. | 9 |
| 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. | 9 |
| 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. | 9 |
| 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. | 9 |
| Total Title | 54 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Related to COVID-19 pandemic | 3 | 4 | 3 | 3 | 3 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Treatment Sequence: ABC | Treatment Sequence: ACB | Treatment Sequence: BAC | Treatment Sequence: BCA | Treatment Sequence: CAB | Treatment Sequence: CBA | Total Title |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 8 Participants | 9 Participants | 9 Participants | 9 Participants | 9 Participants | 53 Participants |
| Age, Continuous | 35.6 years STANDARD_DEVIATION 6.9 | 30.2 years STANDARD_DEVIATION 9.5 | 38.4 years STANDARD_DEVIATION 7.1 | 37.0 years STANDARD_DEVIATION 7.6 | 36.8 years STANDARD_DEVIATION 9.9 | 32.4 years STANDARD_DEVIATION 5.6 | 35.1 years STANDARD_DEVIATION 8.1 |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Other/mixed | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 7 Participants | 9 Participants | 7 Participants | 8 Participants | 5 Participants | 43 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 9 Participants | 9 Participants | 8 Participants | 9 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 51 | 0 / 50 |
| other Total, other adverse events | 38 / 51 | 13 / 51 | 7 / 50 |
| serious Total, serious adverse events | 0 / 51 | 0 / 51 | 0 / 50 |
Outcome results
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 0.75 hour Predose | -1.2 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 0.5 hour Predose | -1.8 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 0.25 hour Predose | -0.7 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 0.25 hour Postdose | -0.5 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 0.5 hour Postdose | -0.9 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 1 hour Postdose | -1.8 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 1.5 hours Postdose | -1.3 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 2 hours Postdose | -1.8 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 3 hours Postdose | -2.5 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 4 hours Postdose | -1.5 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 6 hours Postdose | -0.6 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 8 hours Postdose | -2.0 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 12 hours Postdose | -2.9 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 18 hours Postdose | -4.9 milliseconds (ms) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF on Day 8 for Padsevonil | 24 hours Postdose | -1.5 milliseconds (ms) |
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.
Time frame: Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Padsevonil (QT/QTc Set) | Area Under the Plasma Concentration Time Curve (AUCtau) at Steady State for Padsevonil | 8586 hour*nanogram per milliliter (h*ng/mL) |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Padsevonil (QT/QTc Set) | Change From Baseline in QTcF Evaluated at Drug-specific Tmax for Metabolite 1 | 0.1 milliseconds |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Padsevonil (QT/QTc Set) | Change From Baseline in QTcF Evaluated at Drug-Specific Tmax for Metabolite 2 | -1.0 milliseconds |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Padsevonil (QT/QTc Set) | Change From Baseline in QTcF Evaluated at Drug-specific Tmax for Padsevonil | -1.0 milliseconds |
Secondary
Maximum Observed Plasma Concentration at Steady State (Cmax, ss) for Padsevonil
Cmax,ss: Maximum observed plasma concentration of padsevonil at steady state.
Time frame: Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Padsevonil (QT/QTc Set) | Maximum Observed Plasma Concentration at Steady State (Cmax, ss) for Padsevonil | 2119 nanogram per milliliter (ng/ml) |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Padsevonil (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Flat | 0 Participants |
| Padsevonil (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Notched (+) | 0 Participants |
| Padsevonil (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Biphasic | 1 Participants |
| Padsevonil (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Normal (-) | 0 Participants |
| Padsevonil (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Notched (-) | 0 Participants |
| Padsevonil (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | U-Wave Presence | 0 Participants |
| Moxifloxacin (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | U-Wave Presence | 1 Participants |
| Moxifloxacin (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Flat | 0 Participants |
| Moxifloxacin (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Normal (-) | 0 Participants |
| Moxifloxacin (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Notched (-) | 0 Participants |
| Moxifloxacin (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Notched (+) | 0 Participants |
| Moxifloxacin (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Biphasic | 0 Participants |
| Placebo (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Notched (+) | 0 Participants |
| Placebo (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Biphasic | 0 Participants |
| Placebo (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | U-Wave Presence | 1 Participants |
| Placebo (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Normal (-) | 0 Participants |
| Placebo (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Flat | 0 Participants |
| Placebo (QT/QTc Set) | Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence | Notched (-) | 0 Participants |
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.
Time frame: From Baseline to Safety Follow-up (up to Day 67)
Population: Safety Set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Padsevonil (QT/QTc Set) | Percentage of Participants With Adverse Events From Baseline to Safety Follow-up (up to Day 67) | 88.2 percentage of participants |
| Moxifloxacin (QT/QTc Set) | Percentage of Participants With Adverse Events From Baseline to Safety Follow-up (up to Day 67) | 31.4 percentage of participants |
| Placebo (QT/QTc Set) | Percentage of Participants With Adverse Events From Baseline to Safety Follow-up (up to Day 67) | 20.0 percentage of participants |
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.
Time frame: From Baseline to Safety Follow-up (up to Day 67)
Population: Safety Set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Padsevonil (QT/QTc Set) | Percentage of Participants With Adverse Events Leading to Discontinuation of the Study From Baseline to Safety Follow-up (up to Day 67) | 2.0 percentage of participants |
| Moxifloxacin (QT/QTc Set) | Percentage of Participants With Adverse Events Leading to Discontinuation of the Study From Baseline to Safety Follow-up (up to Day 67) | 0 percentage of participants |
| Placebo (QT/QTc Set) | Percentage of Participants With Adverse Events Leading to Discontinuation of the Study From Baseline to Safety Follow-up (up to Day 67) | 0 percentage of participants |
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: * 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.
Time frame: From Baseline to Safety Follow-up (up to Day 67)
Population: Safety Set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Padsevonil (QT/QTc Set) | Percentage of Participants With Serious Adverse Events From Baseline to Safety Follow-up (up to Day 67) | 0 percentage of participants |
| Moxifloxacin (QT/QTc Set) | Percentage of Participants With Serious Adverse Events From Baseline to Safety Follow-up (up to Day 67) | 0 percentage of participants |
| Placebo (QT/QTc Set) | Percentage of Participants With Serious Adverse Events From Baseline to Safety Follow-up (up to Day 67) | 0 percentage of participants |
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.
Time frame: From Baseline to Safety Follow-up (up to Day 67)
Population: Safety Set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Padsevonil (QT/QTc Set) | Percentage of Participants With Treatment Related Adverse Events From Baseline to Safety Follow-up (up to Day 67) | 86.3 percentage of participants |
| Moxifloxacin (QT/QTc Set) | Percentage of Participants With Treatment Related Adverse Events From Baseline to Safety Follow-up (up to Day 67) | 5.9 percentage of participants |
| Placebo (QT/QTc Set) | Percentage of Participants With Treatment Related Adverse Events From Baseline to Safety Follow-up (up to Day 67) | 4.0 percentage of participants |
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.
Time frame: Day 1 : 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 1 | Day 1: 0.25 hour Postdose | -0.4 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 1 | Day 1: 0.5 hour Postdose | 0.5 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 1 | Day 1: 1 hour Postdose | 2.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 1 | Day 1: 1.5 hours Postdose | 1.9 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 1 | Day 1: 2 hours Postdose | 1.9 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 1 | Day 1: 3 hours Postdose | 2.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 1 | Day 1: 4 hours Postdose | 2.6 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 1 | Day 1: 6 hours Postdose | 2.3 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 1 | Day 1: 8 hours Postdose | 3.5 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 1 | Day 1: 12 hours Postdose | 1.3 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 1 | Day 1: 24 hours Postdose | 1.3 milliseconds |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 0.5 hour Postdose | 3.1 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 3 hours Postdose | 3.6 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 0.5 hour Predose | 1.8 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 4 hours Postdose | 4.1 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 1 hour Postdose | 3.8 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 6 hours Postdose | 3.3 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 0.25 hour Postdose | 2.4 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 8 hours Postdose | 2.6 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 1.5 hours Postdose | 4.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 12 hours Postdose | 1.6 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 0.25 hour Predose | 1.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 18 hours Postdose | -0.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 2 hours Postdose | 3.6 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 24 hours Postdose | -0.6 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 0.75 hour Predose | 2.4 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 24 hours Postdose | -1.9 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 0.75 hour Predose | -0.6 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 0.5 hour Predose | -1.0 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 0.25 hour Predose | -1.2 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 0.25 hour Postdose | -0.4 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 0.5 hour Postdose | -1.6 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 1 hour Postdose | -0.8 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 1.5 hours Postdose | -0.8 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 2 hours Postdose | -1.3 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 3 hours Postdose | -3.1 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 4 hours Postdose | -3.3 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 6 hours Postdose | -2.3 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 8 hours Postdose | -2.3 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 12 hours Postdose | -2.9 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for PR Interval on Day 8 | Day 8: 18 hours Postdose | -2.1 milliseconds |
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.
Time frame: Day 1 : 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 1 | Day 1: 0.25 hour Postdose | -0.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 1 | Day 1: 0.5 hour Postdose | -0.1 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 1 | Day 1: 1 hour Postdose | 0.0 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 1 | Day 1: 1.5 hours Postdose | -0.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 1 | Day 1: 2 hours Postdose | -0.3 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 1 | Day1: 3 hours Postdose | -0.3 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 1 | Day 1: 4 hours Postdose | -0.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 1 | Day1: 6 hours Postdose | -0.1 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 1 | Day1: 8 hours Postdose | -0.3 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 1 | Day1: 12 hours Postdose | 0.1 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 1 | Day1: 24 hours Postdose | -0.3 milliseconds |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 0.5 hour Postdose | -0.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 3 hours Postdose | -0.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 0.5 hour Predose | -0.1 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 4 hours Postdose | -0.3 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 1 hour Postdose | -0.5 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 6 hours Postdose | -0.4 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 0.25 hour Postdose | -0.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 8 hours Postdose | 0.0 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 1.5 hours Postdose | -0.6 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 12 hours Postdose | -0.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 0.25 hour Predose | -0.1 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 18 hours Postdose | -1.1 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 2 hours Postdose | -0.2 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 24 hours Postdose | -0.1 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 0.75 hour Predose | -0.2 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 24 hours Postdose | 0.8 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 0.75 hour Predose | 0.0 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 0.5 hour Predose | 0.0 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 0.25 hour Predose | 0.2 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 0.25 hour Postdose | -0.1 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 0.5 hour Postdose | -0.1 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 1 hour Postdose | 0.0 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 1.5 hours Postdose | -0.1 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 2 hours Postdose | 0.1 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 3 hours Postdose | 0.1 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 4 hours Postdose | 0.0 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 6 hours Postdose | -0.1 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 8 hours Postdose | 0.0 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 12 hours Postdose | 0.5 milliseconds |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline for QRS Interval on Day 8 | Day 8: 18 hours Postdose | -0.1 milliseconds |
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.
Time frame: Day 1 : 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Day 1: 0.25 hour Postdose | 0.2 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Day 1: 0.5 hour Postdose | 2.0 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Day 1: 1 hour Postdose | 1.4 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Day 1: 1.5 hours Postdose | -0.1 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Day 1: 2 hours Postdose | 0.1 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Day 1: 3 hours Postdose | -2.3 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Day 1: 4 hours Postdose | -2.0 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Day 1: 6 hours Postdose | 0.8 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Day 1: 8 hours Postdose | -2.0 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Day 1: 12 hours Postdose | 0.1 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 1 | Day 1: 24 hours Postdose | -0.8 beats per minute (bpm) |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 0.5 hour Postdose | -2.0 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 3 hours Postdose | -2.2 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 0.5 hour Predose | -2.0 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 4 hours Postdose | -1.2 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 1 hour Postdose | -1.9 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 6 hours Postdose | -1.0 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 0.25 hour Postdose | -1.1 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 8 hours Postdose | -3.3 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 1.5 hours Postdose | -1.1 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 12 hours Postdose | -0.6 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 0.25 hour Predose | -1.1 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 18 hours Postdose | 1.1 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 2 hours Postdose | -3.0 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 24 hours Postdose | -1.0 beats per minute (bpm) |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 0.75 hour Predose | -2.0 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 24 hours Postdose | 0.4 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 0.75 hour Predose | -0.4 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 0.5 hour Predose | 0.4 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 0.25 hour Predose | 0.5 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 0.25 hour Postdose | -0.4 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 0.5 hour Postdose | 0.1 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 1 hour Postdose | 1.9 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 1.5 hours Postdose | 1.3 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 2 hours Postdose | 1.0 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 3 hours Postdose | -1.8 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 4 hours Postdose | -0.4 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 6 hours Postdose | 0.2 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 8 hours Postdose | 0.2 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 12 hours Postdose | 0.3 beats per minute (bpm) |
| Moxifloxacin (QT/QTc Set) | Placebo-corrected Change From Baseline in Heart Rate (HR) Interval on Day 8 | Day 8: 18 hours Postdose | 1.3 beats per minute (bpm) |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 0.75 hour Predose | 0.9 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 0.5 hour Predose | 1.9 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 0.25 hour Predose | 2.4 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 0.25 hour Postdose | 1.8 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 0.5 hour Postdose | 3.6 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 1 hour Postdose | 8.6 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 1.5 hours Postdose | 9.8 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 2 hours Postdose | 10.6 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 3 hours Postdose | 9.0 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 4 hours Postdose | 9.0 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 6 hours Postdose | 8.7 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 8 hours Postdose | 8.6 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 12 hours Postdose | 5.5 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 18 hours Postdose | 7.9 milliseconds |
| Padsevonil (QT/QTc Set) | Placebo-corrected Change From Baseline in QTcF After a Single Dose of Moxifloxacin on Day 8 | 24 hours Postdose | 6.3 milliseconds |
Secondary
Time of Observed Maximum Concentration (Tmax) at Steady State for Padsevonil
tmax: Time of observed maximum plasma concentration at steady state.
Time frame: Day 8: 0.5 hours predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 hours postdose
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Padsevonil (QT/QTc Set) | Time of Observed Maximum Concentration (Tmax) at Steady State for Padsevonil | 0.5100 hours (h) |