Epilepsy
Conditions
Keywords
Epilepsy, Phase 1, padsevonil
Brief summary
The purpose of the study is to evaluate the effect of stable coadministered oxcarbazepine (OXC), on the pharmacokinetics (PK), safety, tolerability of padsevonil (PSL) and the plasma PK of PSL metabolites, UCB1431322-000 and UCB1447499-000, in study participants with epilepsy compared with study participants co-medicated with stable doses of levetiracetam (LEV), lamotrigine (LTG) or brivaracetam (BRV) therapy.
Interventions
DRUGPadsevonil
Padsevonil (PSL) will be dosed to steady state and the effect of background therapies on pharmacokinetics will be assessed
DRUGOxcarbazepine
Concomitant administration of oxcarbazepine (OXC) at therapeutic dosage
DRUGLevetiracetam
Concomitant administration of levetiracetam (LEV) at therapeutic dosage
DRUGLamotrigine
Concomitant administration of lamotrigine (LTG) at therapeutic dosage
DRUGBrivaracetam
Concomitant administration of brivaracetam (BRV) at therapeutic dosage
Sponsors
UCB Biopharma S.P.R.L.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Study participant is male or female between 18 to 64 years of age, inclusive, with a diagnosis of epilepsy according to the International League Against Epilepsy (ILAE) classification * Study participant is currently treated for epilepsy with stable doses of the following for at least 3 months: 1. Inducers Group: Oxcarbazepine (OXC) (at least 1200 mg/day as monotherapy or in combination with brivaracetam (BRV) \[up to 200 mg/day\], levetiracetam (LEV) \[at least 1 g/day\] or lamotrigine (LTG) \[at least 150 mg/day\]); or 2. Neutral (control) Group: LTG (at least 150 mg/day monotherapy or adjunctive to LEV or BRV), LEV (at least 1 g/day monotherapy or adjunctive to LTG), or BRV (up to 200 mg/day adjunctive to LTG) * Study participant in the Inducers Group is taking OXC and has a trough OXC metabolite Mono Hydroxy Derivate (MHD) plasma level in the target range (≥12.0 to ≤35.0 mcg/mL) * Study participant has clinical laboratory test results within the local reference ranges or values are considered as not clinically relevant by the Investigator and approved by the UCB Study Physician * Study participant has a body mass index (BMI) of 18 to 35 kg/m², inclusive, with a body weight of at least 50 kg (male) or 45 kg (female) * Female study participant has a negative serum pregnancy test at the Screening Visit and agrees to use an efficient form of contraception for the duration of the study (unless menopausal \[defined as no menses for 12 months without an alternative medical cause\]; a high follicle-stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy). -Male study participant agrees that, during the study period, when having sexual intercourse with a woman of childbearing potential, he will use an efficient barrier contraceptive (condom plus spermicide) AND that the respective partner will use an additional efficient contraceptive method (eg, oral pills, intrauterine device, intrauterine hormone-releasing systems, or diaphragm, and spermicide)
Exclusion criteria
* Study participant has participated in another study of an investigational medication (or a medical device) within the last 3 months before screening (or 5 half-lives, whichever is longer) or is currently participating in another study of an investigational medication (or a medical device) * Study participant has a known hypersensitivity to any components of the IMP as stated in this protocol * Study participant has any medical condition that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study * Study participant has a history of status epilepticus during the last year * Study participant has any clinically relevant electrocardiogram (ECG) finding at the Screening Visit or at Baseline * Study participant has received any prescription or nonprescription medicines, including enzyme inhibitors or inducers, over the counter (OTC) remedies, herbal and dietary supplements (including St. John's Wort), or vitamins up to 2 weeks or 5 half-lives of the respective drug (whichever is longer) before the first administration of IMP and during the clinical part of the study, unless required to treat an Adverse event (AE). This does not include allowed antiepileptic drugs (AEDs) per the protocol, oral contraceptives not exceeding 30 μg ethinyl estradiol or postmenopausal hormone replacement therapy or implants, patches, or IUDs/IUSs delivering progesterone (for female study participants)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Maximum Observed Plasma Concentration (Cmax) of Padsevonil (PSL) During the Study | Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose | The Cmax for Padsevonil in plasma was expressed in nanograms per milliliter (ng/mL). |
| The Time to Reach Maximum Concentration (Tmax) for Padsevonil During the Study | Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose | The tmax for Padsevonil in plasma was expressed in hours (hr). |
| The Area Under the Plasma Concentration Time Curve (AUCtau) Over a Dosing Interval for PSL | Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose | The AUCtau for Padsevonil in plasma was expressed in hours times nanograms per milliliter (hr\*ng/mL). |
| The Apparent Total Plasma Clearance at Steady-state (CL/Fss) for PSL During the Study | Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose | The CL/Fss for Padsevonil in plasma was expressed in liters per hour (L/hr). Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Ratio of PSL Metabolite UCB1431322-000 to PSL Based on the Area Under the Curve (AUCtau) During the Study | Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose | Metabolite-to-Parent Ratios were corrected for differences in molecular weight. Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged). |
| The Maximum Observed Plasma Concentration (Cmax) for UCB1447499-000 During the Study | Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose | The Cmax for UCB1447499-000 in plasma was expressed in ng/mL. Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged). |
| The Time to Reach Maximum Concentration (Tmax) for UCB1447499-000 During the Study | Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose | The tmax for UCB1447499-000 in plasma was expressed in hr. |
| Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Trough plasma samples were taken prior to the morning dose of OXC on Day -1, Day 1 through Day 20 (+/-1) | The trough plasma concentration of MHD with PSL was expressed in micrograms per milliliter (µg/mL). Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged). |
| The Ratio of PSL Metabolite UCB1447499-000 to PSL Based on the Area Under the Curve (AUCtau) | Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose | Metabolite-to-Parent Ratios were corrected for differences in molecular weight. Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged). |
| Percentage of Participants With at Least One Adverse Event (AE) During the Study | From screening (Day -28 to Day -2) up to end of study (EOS) visit day 20 (+/-1) | An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study | From screening (Day -28 to Day -2) up to end of study (EOS) visit day 20 (+/-1) | A SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in patient hospitalization or prolongation of existing hospitalization, was a congenital anomaly or birth defect, was an infection that requires treatment parenteral antibiotics or other important medical events which based on medical or scientific judgement could jeopardize the patients, or could require medical or surgical intervention to prevent any of the above. |
| The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1447499-000 During the Study | Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose | The AUCtau for UCB1447499-000 in plasma was expressed in hr\*ng/mL. Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged). |
| The Maximum Observed Plasma Concentration (Cmax) for UCB1431322-000 During the Study | Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose | The Cmax for UCB1431322-000 in plasma was expressed in nanograms per milliliter (ng/mL). Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged). |
| The Time to Reach Maximum Concentration (Tmax) for UCB1431322-000 During the Study | Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose | The tmax for UCB1431322-000 in plasma was expressed in hours (hr). |
| The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1431322-000 During the Study | Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose | The AUCtau for UCB1431322-000 in plasma in was expressed in hours times nanograms per milliliter (hr\*ng/mL). Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged). |
Countries
Bulgaria, Netherlands
Participant flow
Recruitment details
The study started to enroll patients in September 2018 and concluded in May 2019.
Pre-assignment details
The study included a Screening Period (Day -28 to Day -2), a Baseline Visit (Day -1), a Treatment Period (Day 1 to Day 12) and a Safety Follow-Up Period Day (13 to Day 20±1). Participant Flow refers to the Full Analysis Set.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (Inducers) Participants were on stable therapy with oxcarbazepine (OXC), at least 1200 milligrams per day (mg/day), which could be used as monotherapy or adjunctive to 1 or more of levetiracetam (LEV), lamotrigine (LTG), or brivaracetam (BRV). Padsevonil (PSL) was dosed to steady state (4.5 days) and the effect of background therapy on PSL pharmacokinetics (PK) was assessed at steady state. | 16 |
| Group 2 (Neutral [Control]) Participants were on stable therapy with LTG (at least 150 mg/day monotherapy or adjunctive to LEV or BRV), LEV (at least 1 g/day monotherapy or adjunctive to LTG), or BRV (up to 200 mg/day adjunctive to LTG). Padsevonil (PSL) was dosed to steady state (4.5 days) and the effect of background therapy on PSL pharmacokinetics (PK) was assessed at steady state. | 15 |
| Total Title | 31 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Group 1 (Inducers) | Group 2 (Neutral [Control]) | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 15 Participants | 31 Participants |
| Age, Continuous | 41.4 years STANDARD_DEVIATION 12.1 | 33.6 years STANDARD_DEVIATION 10.4 | 37.6 years STANDARD_DEVIATION 11.8 |
| Race/Ethnicity, Customized Other or mixed | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 16 Participants | 14 Participants | 30 Participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 15 |
| other Total, other adverse events | 16 / 16 | 15 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 15 |
Outcome results
Primary
The Apparent Total Plasma Clearance at Steady-state (CL/Fss) for PSL During the Study
The CL/Fss for Padsevonil in plasma was expressed in liters per hour (L/hr). Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).
Time frame: Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (Inducers) (PK-PPS) | The Apparent Total Plasma Clearance at Steady-state (CL/Fss) for PSL During the Study | 75.44 L/hr | Geometric Coefficient of Variation 34.8 |
| Group 2 (Neutral [Control]) (PK-PPS) | The Apparent Total Plasma Clearance at Steady-state (CL/Fss) for PSL During the Study | 47.94 L/hr | Geometric Coefficient of Variation 39.3 |
Primary
The Area Under the Plasma Concentration Time Curve (AUCtau) Over a Dosing Interval for PSL
The AUCtau for Padsevonil in plasma was expressed in hours times nanograms per milliliter (hr\*ng/mL).
Time frame: Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Group 1 (Inducers) (PK-PPS) | The Area Under the Plasma Concentration Time Curve (AUCtau) Over a Dosing Interval for PSL | 5301 hr*ng/mL |
| Group 2 (Neutral [Control]) (PK-PPS) | The Area Under the Plasma Concentration Time Curve (AUCtau) Over a Dosing Interval for PSL | 8339 hr*ng/mL |
Comparison: The analysis of variance model (ANOVA) included the fixed effects of treatment group. The natural logs were taken of the dependent variables and were back-transformed after the analysis. The geometric mean ratio and the respective 90% confidence interval (CI) was derived for the Inducers group vs the Neutral-control group from the ANOVA model using least-squares means difference.90% CI: [0.504, 0.801]ANOVA
Primary
The Maximum Observed Plasma Concentration (Cmax) of Padsevonil (PSL) During the Study
The Cmax for Padsevonil in plasma was expressed in nanograms per milliliter (ng/mL).
Time frame: Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Group 1 (Inducers) (PK-PPS) | The Maximum Observed Plasma Concentration (Cmax) of Padsevonil (PSL) During the Study | 1210 ng/mL |
| Group 2 (Neutral [Control]) (PK-PPS) | The Maximum Observed Plasma Concentration (Cmax) of Padsevonil (PSL) During the Study | 1670 ng/mL |
Comparison: The analysis of variance model (ANOVA) included the fixed effects of treatment group. The natural logs were taken of the dependent variables and were back-transformed after the analysis. The geometric mean ratio and the respective 90% confidence interval (CI) was derived for the Inducers group vs the Neutral-control group from the ANOVA model using least-squares means difference.90% CI: [0.586, 0.896]ANOVA
Primary
The Time to Reach Maximum Concentration (Tmax) for Padsevonil During the Study
The tmax for Padsevonil in plasma was expressed in hours (hr).
Time frame: Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 (Inducers) (PK-PPS) | The Time to Reach Maximum Concentration (Tmax) for Padsevonil During the Study | 1.500 hr |
| Group 2 (Neutral [Control]) (PK-PPS) | The Time to Reach Maximum Concentration (Tmax) for Padsevonil During the Study | 2.000 hr |
Secondary
Percentage of Participants With at Least One Adverse Event (AE) During the Study
An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: From screening (Day -28 to Day -2) up to end of study (EOS) visit day 20 (+/-1)
Population: The Full Analysis Set (FAS) consisted of all study participants who signed the ICF and received at least 1 dose of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Inducers) (PK-PPS) | Percentage of Participants With at Least One Adverse Event (AE) During the Study | 100 percentage of participants |
| Group 2 (Neutral [Control]) (PK-PPS) | Percentage of Participants With at Least One Adverse Event (AE) During the Study | 100 percentage of participants |
Secondary
Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study
A SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in patient hospitalization or prolongation of existing hospitalization, was a congenital anomaly or birth defect, was an infection that requires treatment parenteral antibiotics or other important medical events which based on medical or scientific judgement could jeopardize the patients, or could require medical or surgical intervention to prevent any of the above.
Time frame: From screening (Day -28 to Day -2) up to end of study (EOS) visit day 20 (+/-1)
Population: The Full Analysis Set (FAS) consisted of all study participants who signed the ICF and received at least 1 dose of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Inducers) (PK-PPS) | Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study | 0 percentage of participants |
| Group 2 (Neutral [Control]) (PK-PPS) | Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study | 0 percentage of participants |
Secondary
The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1431322-000 During the Study
The AUCtau for UCB1431322-000 in plasma in was expressed in hours times nanograms per milliliter (hr\*ng/mL). Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).
Time frame: Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (Inducers) (PK-PPS) | The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1431322-000 During the Study | 11720 hr*ng/mL | Geometric Coefficient of Variation 21.3 |
| Group 2 (Neutral [Control]) (PK-PPS) | The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1431322-000 During the Study | 11200 hr*ng/mL | Geometric Coefficient of Variation 30.7 |
Secondary
The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1447499-000 During the Study
The AUCtau for UCB1447499-000 in plasma was expressed in hr\*ng/mL. Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).
Time frame: Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (Inducers) (PK-PPS) | The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1447499-000 During the Study | 1854 hr*ng/mL | Geometric Coefficient of Variation 29 |
| Group 2 (Neutral [Control]) (PK-PPS) | The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1447499-000 During the Study | 1678 hr*ng/mL | Geometric Coefficient of Variation 28.2 |
Secondary
The Maximum Observed Plasma Concentration (Cmax) for UCB1431322-000 During the Study
The Cmax for UCB1431322-000 in plasma was expressed in nanograms per milliliter (ng/mL). Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).
Time frame: Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (Inducers) (PK-PPS) | The Maximum Observed Plasma Concentration (Cmax) for UCB1431322-000 During the Study | 1753 ng/mL | Geometric Coefficient of Variation 21.7 |
| Group 2 (Neutral [Control]) (PK-PPS) | The Maximum Observed Plasma Concentration (Cmax) for UCB1431322-000 During the Study | 1700 ng/mL | Geometric Coefficient of Variation 29.4 |
Secondary
The Maximum Observed Plasma Concentration (Cmax) for UCB1447499-000 During the Study
The Cmax for UCB1447499-000 in plasma was expressed in ng/mL. Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).
Time frame: Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (Inducers) (PK-PPS) | The Maximum Observed Plasma Concentration (Cmax) for UCB1447499-000 During the Study | 380.1 ng/mL | Geometric Coefficient of Variation 37.8 |
| Group 2 (Neutral [Control]) (PK-PPS) | The Maximum Observed Plasma Concentration (Cmax) for UCB1447499-000 During the Study | 307.2 ng/mL | Geometric Coefficient of Variation 32.6 |
Secondary
The Ratio of PSL Metabolite UCB1431322-000 to PSL Based on the Area Under the Curve (AUCtau) During the Study
Metabolite-to-Parent Ratios were corrected for differences in molecular weight. Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).
Time frame: Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (Inducers) (PK-PPS) | The Ratio of PSL Metabolite UCB1431322-000 to PSL Based on the Area Under the Curve (AUCtau) During the Study | 2.283 ratio | Geometric Coefficient of Variation 22.4 |
| Group 2 (Neutral [Control]) (PK-PPS) | The Ratio of PSL Metabolite UCB1431322-000 to PSL Based on the Area Under the Curve (AUCtau) During the Study | 1.386 ratio | Geometric Coefficient of Variation 48.2 |
Secondary
The Ratio of PSL Metabolite UCB1447499-000 to PSL Based on the Area Under the Curve (AUCtau)
Metabolite-to-Parent Ratios were corrected for differences in molecular weight. Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).
Time frame: Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (Inducers) (PK-PPS) | The Ratio of PSL Metabolite UCB1447499-000 to PSL Based on the Area Under the Curve (AUCtau) | 0.3492 ratio | Geometric Coefficient of Variation 32.8 |
| Group 2 (Neutral [Control]) (PK-PPS) | The Ratio of PSL Metabolite UCB1447499-000 to PSL Based on the Area Under the Curve (AUCtau) | 0.2011 ratio | Geometric Coefficient of Variation 45.7 |
Secondary
The Time to Reach Maximum Concentration (Tmax) for UCB1431322-000 During the Study
The tmax for UCB1431322-000 in plasma was expressed in hours (hr).
Time frame: Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 (Inducers) (PK-PPS) | The Time to Reach Maximum Concentration (Tmax) for UCB1431322-000 During the Study | 3.500 hr |
| Group 2 (Neutral [Control]) (PK-PPS) | The Time to Reach Maximum Concentration (Tmax) for UCB1431322-000 During the Study | 3.500 hr |
Secondary
The Time to Reach Maximum Concentration (Tmax) for UCB1447499-000 During the Study
The tmax for UCB1447499-000 in plasma was expressed in hr.
Time frame: Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 (Inducers) (PK-PPS) | The Time to Reach Maximum Concentration (Tmax) for UCB1447499-000 During the Study | 2.000 hr |
| Group 2 (Neutral [Control]) (PK-PPS) | The Time to Reach Maximum Concentration (Tmax) for UCB1447499-000 During the Study | 2.000 hr |
Secondary
Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL
The trough plasma concentration of MHD with PSL was expressed in micrograms per milliliter (µg/mL). Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).
Time frame: Trough plasma samples were taken prior to the morning dose of OXC on Day -1, Day 1 through Day 20 (+/-1)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Full Analysis Set (FAS), consisting of 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 1 | 14.9 µg/mL | Geometric Coefficient of Variation 14.5 |
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 2 | 14.0 µg/mL | Geometric Coefficient of Variation 21.6 |
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 3 | 14.9 µg/mL | Geometric Coefficient of Variation 17 |
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 4 | 15.5 µg/mL | Geometric Coefficient of Variation 16 |
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 5 | 15.2 µg/mL | Geometric Coefficient of Variation 17.5 |
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 6 | 15.4 µg/mL | Geometric Coefficient of Variation 18.1 |
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 7 | 15.4 µg/mL | Geometric Coefficient of Variation 17 |
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 8 | 16.3 µg/mL | Geometric Coefficient of Variation 16.1 |
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 9 | 15.4 µg/mL | Geometric Coefficient of Variation 13.2 |
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 10 | 15.5 µg/mL | Geometric Coefficient of Variation 13.8 |
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 11 | 15.4 µg/mL | Geometric Coefficient of Variation 18.6 |
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 12 | 13.8 µg/mL | Geometric Coefficient of Variation 20.9 |
| Group 1 (Inducers) (PK-PPS) | Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL | Day 13 | 11.3 µg/mL | Geometric Coefficient of Variation 46.4 |