Trial Outcomes & Findings for Study to Evaluate the Effect of Coadministered Erythromycin on the Pharmacokinetics and Safety of Padsevonil (NCT NCT03480243)
NCT ID: NCT03480243
Last Updated: 2021-07-12
Results Overview
Cmax: The maximum observed plasma concentration of padsevonil for single dose . Cmax was expressed in nanograms per milliliter (ng/mL).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
28 participants
Primary outcome timeframe
Predose and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1, 12, and 26
Results posted on
2021-07-12
Participant Flow
The study started to enroll patients in March 2018 and concluded in August 2018.
Participant Flow refers to the Full Analysis Set (FAS).
Participant milestones
| Measure |
Padsevonil and/or Erythromycin
The study participants received treatment as follows:
Treatment Period 1: From Day 1 to Day 11:
* Padsevonil 100 mg twice daily (bid) on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11).
Treatment Period 2: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22).
Treatment Period 3: From Day 23 to 37
Treatment Period 3a:
-Erythromycin 500 mg bid on Day 23 to Day 25.
Treatment Period 3b:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33.
Treatment Period 3c:
\- Erythromycin 500 mg bid on Day 34 to Day 37.
|
|---|---|
|
Padsevonil (Period 1)
STARTED
|
28
|
|
Padsevonil (Period 1)
COMPLETED
|
28
|
|
Padsevonil (Period 1)
NOT COMPLETED
|
0
|
|
Padsevonil (Period 2)
STARTED
|
28
|
|
Padsevonil (Period 2)
COMPLETED
|
27
|
|
Padsevonil (Period 2)
NOT COMPLETED
|
1
|
|
Erythromycin (Period 3a)
STARTED
|
27
|
|
Erythromycin (Period 3a)
COMPLETED
|
27
|
|
Erythromycin (Period 3a)
NOT COMPLETED
|
0
|
|
Padsevonil and Erythromycin (Period 3b)
STARTED
|
27
|
|
Padsevonil and Erythromycin (Period 3b)
COMPLETED
|
26
|
|
Padsevonil and Erythromycin (Period 3b)
NOT COMPLETED
|
1
|
|
Erythromycin (Period 3c)
STARTED
|
26
|
|
Erythromycin (Period 3c)
COMPLETED
|
26
|
|
Erythromycin (Period 3c)
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Padsevonil and/or Erythromycin
The study participants received treatment as follows:
Treatment Period 1: From Day 1 to Day 11:
* Padsevonil 100 mg twice daily (bid) on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11).
Treatment Period 2: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22).
Treatment Period 3: From Day 23 to 37
Treatment Period 3a:
-Erythromycin 500 mg bid on Day 23 to Day 25.
Treatment Period 3b:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33.
Treatment Period 3c:
\- Erythromycin 500 mg bid on Day 34 to Day 37.
|
|---|---|
|
Padsevonil (Period 2)
Consent withdrawal by subject
|
1
|
|
Padsevonil and Erythromycin (Period 3b)
Un-cooperative behaviour
|
1
|
Baseline Characteristics
Study to Evaluate the Effect of Coadministered Erythromycin on the Pharmacokinetics and Safety of Padsevonil
Baseline characteristics by cohort
| Measure |
Padsevonil and/or Erythromycin
n=28 Participants
The study participants received treatment as follows:
Treatment Period 1: From Day 1 to Day 11:
* Padsevonil 100 mg twice daily (bid) on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11).
Treatment Period 2: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Treatment Period 3: From Day 23 to 37
Treatment Period 3a:
-Erythromycin 500 mg bid on Day 23 to Day 25.
Treatment Period 3b:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33.
Treatment Period 3c:
\- Erythromycin 500 mg bid on Day 34 to Day 37.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=39 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
28 Participants
n=39 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=39 Participants
|
|
Age, Continuous
|
36.7 years
STANDARD_DEVIATION 8.3 • n=39 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=39 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 Participants
n=39 Participants
|
|
Race/Ethnicity, Customized
Black
|
1 Participants
n=39 Participants
|
|
Race/Ethnicity, Customized
White
|
24 Participants
n=39 Participants
|
|
Race/Ethnicity, Customized
Missing
|
1 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: Predose and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1, 12, and 26Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods.
Cmax: The maximum observed plasma concentration of padsevonil for single dose . Cmax was expressed in nanograms per milliliter (ng/mL).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Padsevonil for Single Dose
|
366.6 ng/mL
Geometric Coefficient of Variation 38.8
|
385.3 ng/mL
Geometric Coefficient of Variation 40.9
|
697.4 ng/mL
Geometric Coefficient of Variation 46.9
|
—
|
PRIMARY outcome
Timeframe: Predose and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1, 12, and 26Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods.
AUC(0-12): The area under the plasma concentration-time curve from time zero to 12 hours of padsevonil for single dose . AUC(0-12) was expressed in hours times nanograms per milliliter (hours\*ng/mL).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil for Single Dose
|
1428 hours*ng/mL
Geometric Coefficient of Variation 40.7
|
1571 hours*ng/mL
Geometric Coefficient of Variation 41.8
|
2576 hours*ng/mL
Geometric Coefficient of Variation 47.0
|
—
|
PRIMARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
Cmax, ss: The maximum observed steady-state plasma concentration of padsevonil for multiple doses. Cmax, ss was expressed in nanograms per millilitre (ng/mL).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil for Multiple Doses
|
475.0 ng/mL
Geometric Coefficient of Variation 38.4
|
473.9 ng/mL
Geometric Coefficient of Variation 43.7
|
1010 ng/mL
Geometric Coefficient of Variation 45.7
|
—
|
PRIMARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
AUCtau: The area under the plasma concentration-time curve over a dosing interval (12 hours) of padsevonil for multiple doses. AUC(tau) was expressed in hours times nanograms per millilitre (hours\*ng/mL).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil for Multiple Doses
|
2049 hours*ng/mL
Geometric Coefficient of Variation 41.1
|
2274 hours*ng/mL
Geometric Coefficient of Variation 47.1
|
5073 hours*ng/mL
Geometric Coefficient of Variation 55.9
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment PeriodPopulation: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods.
Tmax: The time of maximum plasma concentration of padsevonil for single dose. Tmax was expressed in hours (h).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Single Dose
|
3.000 hours
Interval 1.0 to 4.05
|
1.500 hours
Interval 0.5 to 4.0
|
1.500 hours
Interval 0.75 to 3.02
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment PeriodPopulation: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods.
Cmin: The minimum observed plasma concentration of padsevonil for single dose. Cmin was expressed in nanograms per millilitre (ng/mL).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Minimum Observed Plasma Concentration (Cmin) of Padsevonil for Single Dose
|
2.857 ng/mL
Geometric Coefficient of Variation 100.9
|
5.643 ng/mL
Geometric Coefficient of Variation 147.8
|
4.286 ng/mL
Geometric Coefficient of Variation 172.5
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
Tmax: The time of maximum plasma concentration of padsevonil for multiple doses. Tmax was expressed in hours (h).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Multiple Doses
|
1.750 hours
Interval 0.5 to 4.0
|
1.500 hours
Interval 0.5 to 4.0
|
2.000 hours
Interval 0.75 to 4.0
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
t½,ss: The apparent terminal elimination half-life at steady-state of padsevonil for multiple doses in plasma. t1/2, ss was expressed in hours (h).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Apparent Terminal Elimination Half-life at Steady-state (t1/2,ss) of Padsevonil for Multiple Doses in Plasma
|
6.465 hours
Interval 4.44 to 11.0
|
6.649 hours
Interval 2.04 to 14.3
|
8.548 hours
Interval 5.54 to 26.9
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
Ctrough: The predose observed plasma concentration of padsevonil for multiple doses. Ctrough was expressed in nanograms per millilitre (ng/mL).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Predose Observed Plasma Concentration (Ctrough) of Padsevonil for Multiple Doses
|
57.03 ng/mL
Geometric Coefficient of Variation 69.0
|
68.57 ng/mL
Geometric Coefficient of Variation 85.1
|
182.6 ng/mL
Geometric Coefficient of Variation 95.5
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
CL/Fss: The apparent total clearance at steady-state of padsevonil for multiple doses in plasma. CL/Fss was expressed in milliliters per hour (mL/hour).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Apparent Total Clearance at Steady-state (CL/Fss) of Padsevonil for Multiple Doses in Plasma
|
48810 mL/hour
Geometric Coefficient of Variation 41.1
|
43970 mL/hour
Geometric Coefficient of Variation 47.1
|
19710 mL/hour
Geometric Coefficient of Variation 55.9
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
lambdaz: The apparent elimination rate constant of padsevonil for multiple doses in plasma. Lambdaz was expressed in liters per hour (l/hour).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Apparent Elimination Rate Constant (Lambdaz) of Padsevonil for Multiple Doses in Plasma
|
0.1049 l\hour
Geometric Coefficient of Variation 27.9
|
0.1006 l\hour
Geometric Coefficient of Variation 36.2
|
0.07975 l\hour
Geometric Coefficient of Variation 34.5
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment PeriodPopulation: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods.
Cmax: The maximum plasma concentration of padsevonil metabolites (1 and 2) for single dose. Cmax was expressed in nanograms per milliliter (ng/mL).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose
Metabolite 1
|
166.6 ng/mL
Geometric Coefficient of Variation 29.1
|
158.7 ng/mL
Geometric Coefficient of Variation 34.5
|
189.5 ng/mL
Geometric Coefficient of Variation 29.8
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose
Metabolite 2
|
110.5 ng/mL
Geometric Coefficient of Variation 33.4
|
94.47 ng/mL
Geometric Coefficient of Variation 44.2
|
108.3 ng/mL
Geometric Coefficient of Variation 49.6
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment PeriodPopulation: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods.
AUC(0-12): The area under the plasma concentration-time curve from time zero to 12 hours of padsevonil metabolites (1 and 2) for single dose. AUC(0-12) was expressed in hours times nanograms per milliliter (hours\*ng/mL).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil Metabolites (1 and 2) for Single Dose
Metabolite 1
|
828.3 hours*ng/mL
Geometric Coefficient of Variation 24.2
|
824.3 hours*ng/mL
Geometric Coefficient of Variation 25.5
|
905.6 hours*ng/mL
Geometric Coefficient of Variation 29.7
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil Metabolites (1 and 2) for Single Dose
Metabolite 2
|
596.5 hours*ng/mL
Geometric Coefficient of Variation 39.0
|
534.4 hours*ng/mL
Geometric Coefficient of Variation 43.9
|
599.5 hours*ng/mL
Geometric Coefficient of Variation 49.5
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
AUCtau: The area under the plasma concentration-time curve over a dosing interval (12 hours) of padsevonil metabolites (1 and 2) for multiple doses. AUCtau was expressed in hours times nanograms per milliliter (hours\*ng/mL).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses
Metabolite 1
|
1748 hours*ng/mL
Geometric Coefficient of Variation 35.1
|
1993 hours*ng/mL
Geometric Coefficient of Variation 40.8
|
2625 hours*ng/mL
Geometric Coefficient of Variation 46.1
|
—
|
|
Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses
Metabolite 2
|
775.1 hours*ng/mL
Geometric Coefficient of Variation 37.4
|
813.1 hours*ng/mL
Geometric Coefficient of Variation 40.5
|
799.0 hours*ng/mL
Geometric Coefficient of Variation 38.5
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
Cmax, ss: The maximum observed steady-state plasma concentration of padsevonil metabolites (1 and 2) for multiple doses. Cmax, ss was expressed in nanograms per millilitre (ng/mL).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses
Metabolite 1
|
232.3 ng/mL
Geometric Coefficient of Variation 27.1
|
258.3 ng/mL
Geometric Coefficient of Variation 32.3
|
310.3 ng/mL
Geometric Coefficient of Variation 46.0
|
—
|
|
Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses
Metabolite 2
|
118.6 ng/mL
Geometric Coefficient of Variation 29.3
|
113.3 ng/mL
Geometric Coefficient of Variation 36.8
|
101.8 ng/mL
Geometric Coefficient of Variation 37.1
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 12 hours post dose of Padsevonil for each Treatment PeriodPopulation: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods.
Metabolite-to-parent ratio calculated as: Cmax of padsevonil metabolites (1 and 2) divided by Cmax of padsevonil following a single dose in plasma. Metabolite-to-parent ratio for Cmax was expressed as ratio.
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma
Metabolite 1
|
0.4544 ratio
Geometric Coefficient of Variation 40.6
|
0.4119 ratio
Geometric Coefficient of Variation 45.5
|
0.2717 ratio
Geometric Coefficient of Variation 49.5
|
—
|
|
Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma
Metabolite 2
|
0.3015 ratio
Geometric Coefficient of Variation 66.8
|
0.2452 ratio
Geometric Coefficient of Variation 77.1
|
0.1552 ratio
Geometric Coefficient of Variation 94.3
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment PeriodPopulation: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods.
Metabolite-to-parent ratio calculated as: AUC(0-12)of padsevonil metabolites (1 and 2) divided by AUC(0-12) of padsevonil following a single dose in plasma. Metabolite-to-parent ratio for AUC(0-12) was expressed as ratio.
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma
Metabolite 1
|
0.5799 ratio
Geometric Coefficient of Variation 39.7
|
0.5246 ratio
Geometric Coefficient of Variation 42.8
|
0.3515 ratio
Geometric Coefficient of Variation 48.9
|
—
|
|
Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma
Metabolite 2
|
0.4176 ratio
Geometric Coefficient of Variation 70.0
|
0.3401 ratio
Geometric Coefficient of Variation 78.7
|
0.2327 ratio
Geometric Coefficient of Variation 97.1
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
Metabolite-to-parent ratio calculated as: AUCtau of padsevonil metabolites (1 and 2) divided by AUCtau of padsevonil following multiple dosing in plasma. Metabolite-to-parent ratio for AUCtau was expressed as ratio.
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma
Metabolite 1
|
0.8533 ratio
Geometric Coefficient of Variation 34.9
|
0.8766 ratio
Geometric Coefficient of Variation 38.7
|
0.5174 ratio
Geometric Coefficient of Variation 48.2
|
—
|
|
Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma
Metabolite 2
|
0.3783 ratio
Geometric Coefficient of Variation 63.4
|
0.3576 ratio
Geometric Coefficient of Variation 75.5
|
0.1575 ratio
Geometric Coefficient of Variation 88.5
|
—
|
SECONDARY outcome
Timeframe: Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment PeriodPopulation: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods.
CLr: The renal clearance of padsevonil and its metabolites (1 and 2) for single dose in urine. CLr was expressed in milliliters per hour (mL/hour).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine
Padsevonil
|
27.40 mL/hour
Geometric Coefficient of Variation 54.3
|
25.80 mL/hour
Geometric Coefficient of Variation 73.0
|
19.36 mL/hour
Geometric Coefficient of Variation 60.2
|
—
|
|
Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine
Metabolite 1
|
253.7 mL/hour
Geometric Coefficient of Variation 47.8
|
283.0 mL/hour
Geometric Coefficient of Variation 60.1
|
255.0 mL/hour
Geometric Coefficient of Variation 53.9
|
—
|
|
Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine
Metabolite 2
|
17640 mL/hour
Geometric Coefficient of Variation 19.6
|
17630 mL/hour
Geometric Coefficient of Variation 21.2
|
16290 mL/hour
Geometric Coefficient of Variation 20.7
|
—
|
SECONDARY outcome
Timeframe: Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
CLr: The renal clearance of padsevonil and its metabolites (1 and 2) for multiple doses in urine. CLr was expressed in milliliters per hour (mL/hour).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine
Padsevonil
|
28.43 mL/hours
Geometric Coefficient of Variation 58.0
|
25.24 mL/hours
Geometric Coefficient of Variation 59.7
|
25.12 mL/hours
Geometric Coefficient of Variation 56.1
|
—
|
|
Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine
Metabolite 1
|
335.0 mL/hours
Geometric Coefficient of Variation 50.2
|
325.4 mL/hours
Geometric Coefficient of Variation 40.8
|
311.4 mL/hours
Geometric Coefficient of Variation 51.7
|
—
|
|
Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine
Metabolite 2
|
19390 mL/hours
Geometric Coefficient of Variation 24.9
|
18530 mL/hours
Geometric Coefficient of Variation 20.7
|
16470 mL/hours
Geometric Coefficient of Variation 27.6
|
—
|
SECONDARY outcome
Timeframe: Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment PeriodPopulation: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods.
Ae: The cumulative amount of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for single dose. Ae was expressed in milligrams (mg).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose
Padsevonil
|
0.03914 milligrams
Geometric Coefficient of Variation 57.5
|
0.04054 milligrams
Geometric Coefficient of Variation 75.0
|
0.04987 milligrams
Geometric Coefficient of Variation 74.6
|
—
|
|
Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose
Metabolite 1
|
0.2101 milligrams
Geometric Coefficient of Variation 43.2
|
0.2333 milligrams
Geometric Coefficient of Variation 52.1
|
0.2309 milligrams
Geometric Coefficient of Variation 45.8
|
—
|
|
Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose
Metabolite 2
|
10.53 milligrams
Geometric Coefficient of Variation 42.5
|
9.423 milligrams
Geometric Coefficient of Variation 45.5
|
9.764 milligrams
Geometric Coefficient of Variation 53.1
|
—
|
|
Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose
Metabolite 3
|
29.11 milligrams
Geometric Coefficient of Variation 39.3
|
27.44 milligrams
Geometric Coefficient of Variation 42.3
|
26.09 milligrams
Geometric Coefficient of Variation 40.6
|
—
|
SECONDARY outcome
Timeframe: Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
Ae: The cumulative amount of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for multiple doses. Ae was expressed in milligrams (mg).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses
Padsevonil
|
0.05825 milligrams
Geometric Coefficient of Variation 57.2
|
0.05741 milligrams
Geometric Coefficient of Variation 58.6
|
0.1274 milligrams
Geometric Coefficient of Variation 62.3
|
—
|
|
Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses
Metabolite 1
|
0.6188 milligrams
Geometric Coefficient of Variation 45.3
|
0.6657 milligrams
Geometric Coefficient of Variation 45.0
|
0.8797 milligrams
Geometric Coefficient of Variation 46.8
|
—
|
|
Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses
Metabolite 2
|
15.03 milligrams
Geometric Coefficient of Variation 45.8
|
15.07 milligrams
Geometric Coefficient of Variation 46.9
|
13.67 milligrams
Geometric Coefficient of Variation 41.4
|
—
|
|
Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses
Metabolite 3
|
70.83 milligrams
Geometric Coefficient of Variation 30.7
|
65.30 milligrams
Geometric Coefficient of Variation 34.0
|
81.36 milligrams
Geometric Coefficient of Variation 30.7
|
—
|
SECONDARY outcome
Timeframe: Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment PeriodPopulation: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods.
fe: The fraction of padsevonil or metabolites (1, 2, and 3) excreted into the urine for single dose. fe was expressed in percentage (%).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose
Padsevonil
|
0.03914 percentage excreted
Geometric Coefficient of Variation 57.5
|
0.04054 percentage excreted
Geometric Coefficient of Variation 75.0
|
0.04987 percentage excreted
Geometric Coefficient of Variation 74.6
|
—
|
|
Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose
Metabolite 1
|
0.2170 percentage excreted
Geometric Coefficient of Variation 43.2
|
0.2410 percentage excreted
Geometric Coefficient of Variation 52.1
|
0.2385 percentage excreted
Geometric Coefficient of Variation 45.8
|
—
|
|
Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose
Metabolite 2
|
10.52 percentage excreted
Geometric Coefficient of Variation 42.5
|
9.419 percentage excreted
Geometric Coefficient of Variation 45.5
|
9.760 percentage excreted
Geometric Coefficient of Variation 53.1
|
—
|
|
Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose
Metabolite 3
|
21.17 percentage excreted
Geometric Coefficient of Variation 39.3
|
19.96 percentage excreted
Geometric Coefficient of Variation 42.3
|
18.98 percentage excreted
Geometric Coefficient of Variation 40.6
|
—
|
SECONDARY outcome
Timeframe: Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
fe: The fraction of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for multiple doses. fe was expressed in percentage (%).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses
Metabolite 3
|
51.52 percentage excreted
Geometric Coefficient of Variation 30.7
|
47.50 percentage excreted
Geometric Coefficient of Variation 34.0
|
56.69 percentage excreted
Geometric Coefficient of Variation 38.0
|
—
|
|
Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses
Padsevonil
|
0.05825 percentage excreted
Geometric Coefficient of Variation 57.2
|
0.05741 percentage excreted
Geometric Coefficient of Variation 58.6
|
0.1274 percentage excreted
Geometric Coefficient of Variation 62.3
|
—
|
|
Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses
Metabolite 1
|
0.6049 percentage excreted
Geometric Coefficient of Variation 45.6
|
0.6700 percentage excreted
Geometric Coefficient of Variation 44.6
|
0.8443 percentage excreted
Geometric Coefficient of Variation 45.3
|
—
|
|
Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses
Metabolite 2
|
15.02 percentage excreted
Geometric Coefficient of Variation 45.8
|
15.06 percentage excreted
Geometric Coefficient of Variation 46.9
|
13.15 percentage excreted
Geometric Coefficient of Variation 37.9
|
—
|
SECONDARY outcome
Timeframe: Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment PeriodPopulation: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods.
CLform: The formation clearance of padsevonil metabolites (1, 2, and 3) in the urine for single dose. CLform was expressed in milliliters per hour (mL/hour).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose
Metabolite 2
|
7365 mL/hour
Geometric Coefficient of Variation 80.2
|
5994 mL/hour
Geometric Coefficient of Variation 87.8
|
3788 mL/hour
Geometric Coefficient of Variation 107.5
|
—
|
|
Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose
Metabolite 3
|
14820 mL/hour
Geometric Coefficient of Variation 60.5
|
12700 mL/hour
Geometric Coefficient of Variation 59.9
|
7367 mL/hour
Geometric Coefficient of Variation 72.0
|
—
|
|
Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose
Metabolite 1
|
151.9 mL/hour
Geometric Coefficient of Variation 67.3
|
153.4 mL/hour
Geometric Coefficient of Variation 75.8
|
92.59 mL/hour
Geometric Coefficient of Variation 80.8
|
—
|
SECONDARY outcome
Timeframe: Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
CLform: The formation clearance of padsevonil metabolites (1, 2, and 3) in the urine for multiple doses. CLform was expressed in milliliters per hour (mL/hour).
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=26 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses
Metabolite 1
|
295.3 mL/h
Geometric Coefficient of Variation 63.2
|
294.6 mL/h
Geometric Coefficient of Variation 58.9
|
166.4 mL/h
Geometric Coefficient of Variation 63.8
|
—
|
|
Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses
Metabolite 2
|
7331 mL/h
Geometric Coefficient of Variation 80.5
|
6622 mL/h
Geometric Coefficient of Variation 90.9
|
2593 mL/h
Geometric Coefficient of Variation 93.9
|
—
|
|
Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses
Metabolite 3
|
25150 mL/h
Geometric Coefficient of Variation 44.7
|
20890 mL/h
Geometric Coefficient of Variation 48.1
|
11170 mL/h
Geometric Coefficient of Variation 58.7
|
—
|
SECONDARY outcome
Timeframe: From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days )Population: The Full Analysis Set (FAS) consisted of all study participants who have signed the Informed Consent form (ICF) and received investigational medicinal product (IMP). The analysis of this outcome measure was performed according to the treatment the participants actually received.
An 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 an 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.
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
n=26 Participants
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) During the Study
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days )Population: The FAS consisted of all study participants who have signed the Informed Consent form ICF and received IMP. The analysis of this outcome measure was performed according to the treatment the participants actually received.
Treatment-emergent Adverse Events (TEAEs) were defined as those events which started on or after the date of first dose of UP0057 IMP, or events in which severity worsened on or after the date of first dose of UP0057 study medication.
Outcome measures
| Measure |
Padsevonil (Period 1) (PK-PPS)
n=28 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 1 as follows: From Day 1 to Day 11:
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11). Study participants formed the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
Padsevonil (Period 2) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the PK-PPS.
|
Padsevonil and Erythromycin (Period 3b) (PK-PPS)
n=27 Participants
The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the PK-PPS.
|
Erythromycin (Period 3c) (FAS)
n=26 Participants
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
Percentage of Participants Experiencing Treatment-Emergent Non-serious Adverse Events (AEs) During the Study
|
100 percentage of participants
|
11.1 percentage of participants
|
96.3 percentage of participants
|
19.2 percentage of participants
|
Adverse Events
Padsevonil (Period 1+2) (FAS)
Serious events: 0 serious events
Other events: 28 other events
Deaths: 0 deaths
Erythromycin (Period 3a) (FAS)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Padsevonil and Erythromycin (Period 3b) (FAS)
Serious events: 0 serious events
Other events: 25 other events
Deaths: 0 deaths
Erythromycin (Period 3c) (FAS)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Padsevonil (Period 1+2) (FAS)
n=28 participants at risk
Treatment Period 1 (Day 1 to Day 11):
* Padsevonil 100 mg bid on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11)
Treatment Period 2 (Day 12 to 22):
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Study participants formed the Full Analysis Set (FAS).
|
Erythromycin (Period 3a) (FAS)
n=27 participants at risk
Study participants received Erythromycin in Treatment Period 3a as follows: 500 mg bid on Day 23 to Day 25. Study participants formed the FAS.
|
Padsevonil and Erythromycin (Period 3b) (FAS)
n=27 participants at risk
Study participants received Padsevonil and Erythromycin in Treatment Period 3b as follows:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33. Study participants formed the FAS.
|
Erythromycin (Period 3c) (FAS)
n=26 participants at risk
Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS.
|
|---|---|---|---|---|
|
General disorders
Medical device site reaction
|
17.9%
5/28 • Number of events 5 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
25.9%
7/27 • Number of events 7 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/26 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.7%
3/28 • Number of events 3 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/26 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
|
Nervous system disorders
Dizziness
|
64.3%
18/28 • Number of events 27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
29.6%
8/27 • Number of events 8 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/26 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
|
Nervous system disorders
Headache
|
17.9%
5/28 • Number of events 6 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
7.7%
2/26 • Number of events 2 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
|
Nervous system disorders
Paraesthesia
|
7.1%
2/28 • Number of events 2 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/26 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
|
Nervous system disorders
Somnolence
|
100.0%
28/28 • Number of events 50 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
92.6%
25/27 • Number of events 27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/26 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
|
Psychiatric disorders
Depressed mood
|
7.1%
2/28 • Number of events 2 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/26 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
|
Psychiatric disorders
Euphoric mood
|
21.4%
6/28 • Number of events 6 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
18.5%
5/27 • Number of events 5 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/26 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
|
Psychiatric disorders
Insomnia
|
7.1%
2/28 • Number of events 3 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/26 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.1%
2/28 • Number of events 2 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/27 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
0.00%
0/26 • From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60