Healthy Study Participants, Impaired Hepatic Function
Conditions
Keywords
Padsevonil, Phase 1, Pharmacokinetic, PSL
Brief summary
The purpose of the study is to evaluate the plasma pharmacokinetic (PK), safety and tolerability of padsevonil (PSL) in hepatically impaired and non-hepatically impaired study participants.
Interventions
DRUGPadsevonil
Padsevonil will be administered in predefined dosages.
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 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be male or female 18 to 70 years of age, inclusive, at the time of signing the informed consent * Participant must have body weight of at least 50 kg (males) or 45 kg (females) and body mass index within the range 18 to 38 kg/m\^2 (inclusive) * Participants must meet the following requirements to be included in the study: 1. A male participant must agree to use contraception during both Treatment Periods and for at least 7 days after the last dose of study medication and refrain from donating sperm during this period 2. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance during both Treatment Periods and for at least 90 days (or 5 terminal half-lives) after the final dose of study medication Specific inclusion criteria for study participants WITH moderate hepatic insufficiency: * Participant must have characteristics that will meet the clinical criteria usually found in participants with chronic hepatic insufficiency, as determined by medical history and physical examinations (eg, echography, scintigraphy, biopsy, or some specific laboratory values as evidence)
Exclusion criteria
* Participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or compromise the study participant's ability to participate in this study, such as a history of schizophrenia, or other psychotic disorder, bipolar disorder, or severe unipolar depression. The presence of potential psychiatric
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve (AUCtau) at Steady-state Over a Dosing Interval of Multiple Doses Padsevonil (PSL) | On Days 8, 9, 10 and 11 PK samples were taken predose. On Day 12, PK samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24 hours postdose | AUCtau is defined as area under the curve over a dosing interval at steady-state. |
| Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL) | Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose | AUC (0-t) is defined as area under the plasma concentration-time curve from time zero to time t. |
| Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity of a Single Dose Padsevonil (PSL) | Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose | AUC is defined as area under the plasma concentration-time curve from time 0 to infinity. |
| Maximum Observed Plasma Concentration at Steady-state (Cmax,ss) of Multiple Doses Padsevonil (PSL) | On Days 8, 9, 10 and 11 PK samples were taken predose. On Day 12, PK samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24 hours postdose | Cmax,ss is defined as maximum observed plasma concentration at steady-state. |
| Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL) | Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose | Cmax is maximum observed plasma concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs) | From Baseline until End of Study Visit (up to Day 18) | A serious adverse event (SAE) is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires in patient hospitalization or prolongation of existing hospitalization * Is a congenital anomaly or birth defect * Is 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation of the Study | From Baseline until End of Study Visit (up to Day 18) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event was characterized according to the intake of the study medication. TEAEs leading to discontinuation of the study are reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From Baseline until End of Study Visit (up to Day 18) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event was characterized according to the intake of the study medication. |
Countries
United States
Participant flow
Recruitment details
The study started to enroll study participants in October 2019 and concluded in May 2020.
Pre-assignment details
Participant Flow refers to the Safety Set (SS).
Participants by arm
| Arm | Count |
|---|---|
| Cohort A Healthy study participants in Cohort A received a single dose of padsevonil 100 milligrams (mg) on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg twice daily (bid) from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. There was a Washout Period of 6 days between Treatment Period 1 and 2. | 3 |
| Cohort B Participants with moderate hepatic insufficiency in Cohort B received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. There was a Washout Period of 6 days between Treatment Period 1 and 2. | 9 |
| Total Title | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Sponsor request due to undisclosed concomitant medication | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort A | Cohort B | 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 | 3 Participants | 9 Participants | 12 Participants |
| Age, Continuous | 57.0 years STANDARD_DEVIATION 7.5 | 57.8 years STANDARD_DEVIATION 4.3 | 57.6 years STANDARD_DEVIATION 4.9 |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 1 Participants | 6 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 9 | 0 / 3 | 0 / 9 |
| other Total, other adverse events | 3 / 3 | 6 / 9 | 3 / 3 | 7 / 9 |
| serious Total, serious adverse events | 0 / 3 | 0 / 9 | 0 / 3 | 0 / 9 |
Outcome results
Primary
Area Under the Concentration-time Curve (AUCtau) at Steady-state Over a Dosing Interval of Multiple Doses Padsevonil (PSL)
AUCtau is defined as area under the curve over a dosing interval at steady-state.
Time frame: On Days 8, 9, 10 and 11 PK samples were taken predose. On Day 12, PK samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24 hours postdose
Population: The Pharmacokinetic Set (PKS) is a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and had a sufficient number of samples available to determine at least 1 PK parameter. All PK analyses were performed using the PKS.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort A (PKS) | Area Under the Concentration-time Curve (AUCtau) at Steady-state Over a Dosing Interval of Multiple Doses Padsevonil (PSL) | NA hours*ng/mL |
| Cohort B (PKS) | Area Under the Concentration-time Curve (AUCtau) at Steady-state Over a Dosing Interval of Multiple Doses Padsevonil (PSL) | 3783 hours*ng/mL |
Primary
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity of a Single Dose Padsevonil (PSL)
AUC is defined as area under the plasma concentration-time curve from time 0 to infinity.
Time frame: Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose
Population: The Pharmacokinetic Set (PKS) is a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and had a sufficient number of samples available to determine at least 1 PK parameter. All PK analyses were performed using the PKS.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort A (PKS) | Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity of a Single Dose Padsevonil (PSL) | NA hours*ng/mL |
| Cohort B (PKS) | Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity of a Single Dose Padsevonil (PSL) | 3830 hours*ng/mL |
Primary
Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL)
AUC (0-t) is defined as area under the plasma concentration-time curve from time zero to time t.
Time frame: Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose
Population: The Pharmacokinetic Set (PKS) is a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and had a sufficient number of samples available to determine at least 1 PK parameter. All PK analyses were performed using the PKS.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort A (PKS) | Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL) | NA hours*nanograms per milliliter (h*ng/mL) |
| Cohort B (PKS) | Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL) | 3793 hours*nanograms per milliliter (h*ng/mL) |
Primary
Maximum Observed Plasma Concentration at Steady-state (Cmax,ss) of Multiple Doses Padsevonil (PSL)
Cmax,ss is defined as maximum observed plasma concentration at steady-state.
Time frame: On Days 8, 9, 10 and 11 PK samples were taken predose. On Day 12, PK samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24 hours postdose
Population: The Pharmacokinetic Set (PKS) is a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and had a sufficient number of samples available to determine at least 1 PK parameter. All PK analyses were performed using the PKS.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort A (PKS) | Maximum Observed Plasma Concentration at Steady-state (Cmax,ss) of Multiple Doses Padsevonil (PSL) | NA nanograms per milliliter (ng/mL) |
| Cohort B (PKS) | Maximum Observed Plasma Concentration at Steady-state (Cmax,ss) of Multiple Doses Padsevonil (PSL) | 558.1 nanograms per milliliter (ng/mL) |
Primary
Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL)
Cmax is maximum observed plasma concentration.
Time frame: Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose
Population: The Pharmacokinetic Set (PKS) is a subset of the Full Analysis Set (FAS), consisting of those study participants who had no important protocol deviations affecting the PK parameters and had a sufficient number of samples available to determine at least 1 PK parameter. All PK analyses were performed using the PKS.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort A (PKS) | Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL) | NA nanograms/milliliter (ng/mL) |
| Cohort B (PKS) | Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL) | 531.4 nanograms/milliliter (ng/mL) |
Secondary
Number of Participants With Serious Adverse Events (SAEs)
A serious adverse event (SAE) is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires in patient hospitalization or prolongation of existing hospitalization * Is a congenital anomaly or birth defect * Is 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.
Time frame: From Baseline until End of Study Visit (up to Day 18)
Population: The Safety Set (SS) consisted of all study participants who received at least 1 dose of the investigational medicinal product (IMP). Study participants were classified according to the treatment that was actually received. All safety analyses were performed using the SS.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A (PKS) | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
| Cohort B (PKS) | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
| Cohort A Multiple Dose (SS) | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
| Cohort B Multiple Dose (SS) | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event was characterized according to the intake of the study medication.
Time frame: From Baseline until End of Study Visit (up to Day 18)
Population: The Safety Set (SS) consisted of all study participants who received at least 1 dose of the investigational medicinal product (IMP). Study participants were classified according to the treatment that was actually received. All safety analyses were performed using the SS.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A (PKS) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Cohort B (PKS) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
| Cohort A Multiple Dose (SS) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Cohort B Multiple Dose (SS) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 7 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation of the Study
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event was characterized according to the intake of the study medication. TEAEs leading to discontinuation of the study are reported.
Time frame: From Baseline until End of Study Visit (up to Day 18)
Population: The Safety Set (SS) consisted of all study participants who received at least 1 dose of the investigational medicinal product (IMP). Study participants were classified according to the treatment that was actually received. All safety analyses were performed using the SS.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A (PKS) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation of the Study | 0 Participants |
| Cohort B (PKS) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation of the Study | 0 Participants |
| Cohort A Multiple Dose (SS) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation of the Study | 0 Participants |
| Cohort B Multiple Dose (SS) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation of the Study | 0 Participants |