A Study in Participants With Epilepsy, to Evaluate the Pharmacokinetics, Safety and Tolerability of Oxcarbazepine on Padsevonil

• Sponsor: UCB Biopharma S.P.R.L. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03695094
• Collaborator: (none)
• Enrollment: 31
• Locations: 2
• Arms: 2
• Actual Duration (Months): 8.3
• Patients Per Site: 15.5
• Patients Per Site Per Month: 1.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Padsevonil; Drug: Oxcarbazepine; Drug: Levetiracetam; Drug: Lamotrigine; Drug: Brivaracetam	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Multicenter, Open-label, Parallel-group Study in Study Participants With Epilepsy, to Evaluate the Effect of Oxcarbazepine on the Pharmacokinetics, Safety, and Tolerability of Padsevonil
• Actual Study Start Date: Sep 18, 2018
• Actual Primary Completion Date: May 18, 2019
• Actual Study Completion Date: May 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Cohort 1 (Inducers): Study participants on stable therapy with oxcarbazepine (OXC) either as monotherapy or adjunctive to levetiracetam (LEV), lamotrigine (LTG), or brivaracetam (BRV). OXC may be used as monotherapy or in combination with 1 or more of LEV, LTG, or BRV. Padsevonil (PSL) will be dosed to steady state and the effect of background therapy on PSL pharmacokinetics will be assessed at steady state.	Drug: Padsevonil; Padsevonil (PSL) will be dosed to steady state and the effect of background therapies on pharmacokinetics will be assessed; Other Names: PSL UCB0942 ; Drug: Oxcarbazepine; Concomitant administration of oxcarbazepine (OXC) at therapeutic dosage; Other Names: OXC ; Drug: Levetiracetam; Concomitant administration of levetiracetam (LEV) at therapeutic dosage; Other Names: LEV ; Drug: Lamotrigine; Concomitant administration of lamotrigine (LTG) at therapeutic dosage; Other Names: LTG ; Drug: Brivaracetam; Concomitant administration of brivaracetam (BRV) at therapeutic dosage; Other Names: BRV
Experimental: Cohort 2 Cohort 2 (Neutral): Study participants on stable therapy with lamotrigine (LTG), levetiracetam (LEV), or brivaracetam (BRV). LTG or LEV may be used as monotherapy or in combination with each other. BRV may only be used in combination with LTG. LTG or LEV may be used as monotherapy or in combination with each other. BRV may only be used in combination with LTG. Padsevonil (PSL) will be dosed to steady state (4.5 days) and the effect of background therapy on PSL pharmacokinetics will be assessed at steady state.	Drug: Padsevonil; Padsevonil (PSL) will be dosed to steady state and the effect of background therapies on pharmacokinetics will be assessed; Other Names: PSL UCB0942 ; Drug: Levetiracetam; Concomitant administration of levetiracetam (LEV) at therapeutic dosage; Other Names: LEV ; Drug: Lamotrigine; Concomitant administration of lamotrigine (LTG) at therapeutic dosage; Other Names: LTG ; Drug: Brivaracetam; Concomitant administration of brivaracetam (BRV) at therapeutic dosage; Other Names: BRV

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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).

3. 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).

4. 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 Outcome Measures

1. 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).

2. 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).

3. 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).

4. 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).

5. 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).

6. 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).

7. 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.

8. 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).

9. 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).

10. 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.

11. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Up0070 101	Sofia		Bulgaria
2	Up0070 401	Leiden		Netherlands

Sponsors and Collaborators

• UCB Biopharma S.P.R.L.

Investigators

• Study Director: UCB Cares, 001 844 599 2273 (UCB)

Study Documents (Full-Text)

• Study Protocol - Jun 8, 2018
• Statistical Analysis Plan - Oct 26, 2018

More Information

Publications

None provided.

• Responsible Party: UCB Biopharma S.P.R.L.
• ClinicalTrials.gov Identifier: NCT03695094
• Other Study ID Numbers: UP0070; 2018-001941-16
• First Posted: Oct 3, 2018
• Last Update Posted: Jun 4, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by UCB Biopharma S.P.R.L.: Epilepsy; Phase 1; padsevonil
• Additional relevant MeSH terms: Epilepsy; Lamotrigine; Oxcarbazepine; Levetiracetam; Brivaracetam

Study Results

Participant Flow

Recruitment Details	The study started to enroll patients in September 2018 and concluded in May 2019.
Pre-assignment Detail	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.

Arm/Group Title	Group 1 (Inducers)	Group 2 (Neutral [Control])
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	16	15
COMPLETED	14	14
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Group 1 (Inducers)	Group 2 (Neutral [Control])	Total Title
Arm/Group Description	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.	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.
Overall Participants	16	15	31
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 100%	15 100%	31 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.4 (12.1)	33.6 (10.4)	37.6 (11.8)
Sex: Female, Male (Count of Participants)
Female	7 43.8%	9 60%	16 51.6%
Male	9 56.3%	6 40%	15 48.4%
Race/Ethnicity, Customized (Count of Participants)
White	16 100%	14 93.3%	30 96.8%
Other or mixed	0 0%	1 6.7%	1 3.2%

Outcome Measures

1. Primary Outcome

Title	The Maximum Observed Plasma Concentration (Cmax) of Padsevonil (PSL) During the Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)	Group 2 (Neutral [Control]) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).	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. Participants formed the PK-PPS.
Measure Participants	14	14
Least Squares Mean (95% Confidence Interval) [ng/mL]	1210	1670

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1 (Inducers) (PK-PPS), Group 2 (Neutral [Control]) (PK-PPS)
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.725
	Confidence Interval	(2-Sided) 90%; 0.586 to 0.896
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	The Time to Reach Maximum Concentration (Tmax) for Padsevonil During the Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)	Group 2 (Neutral [Control]) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).	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. Participants formed the PK-PPS.
Measure Participants	14	14
Median (Full Range) [hr]	1.500	2.000

3. Primary Outcome

Title	The Area Under the Plasma Concentration Time Curve (AUCtau) Over a Dosing Interval for PSL
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)	Group 2 (Neutral [Control]) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).	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. Participants formed the PK-PPS.
Measure Participants	14	14
Least Squares Mean (95% Confidence Interval) [hr*ng/mL]	5301	8339

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1 (Inducers) (PK-PPS), Group 2 (Neutral [Control]) (PK-PPS)
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.636
	Confidence Interval	(2-Sided) 90%; 0.504 to 0.801
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	The Apparent Total Plasma Clearance at Steady-state (CL/Fss) for PSL During the Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)	Group 2 (Neutral [Control]) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).	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. Participants formed the PK-PPS.
Measure Participants	14	14
Geometric Mean (Geometric Coefficient of Variation) [L/hr]	75.44 (34.8)	47.94 (39.3)

5. Secondary Outcome

Title	Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).
Measure Participants	14
Day 1	14.9 (14.5)
Day 2	14.0 (21.6)
Day 3	14.9 (17.0)
Day 4	15.5 (16.0)
Day 5	15.2 (17.5)
Day 6	15.4 (18.1)
Day 7	15.4 (17.0)
Day 8	16.3 (16.1)
Day 9	15.4 (13.2)
Day 10	15.5 (13.8)
Day 11	15.4 (18.6)
Day 12	13.8 (20.9)
Day 13	11.3 (46.4)

6. Secondary Outcome

Title	The Maximum Observed Plasma Concentration (Cmax) for UCB1431322-000 During the Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)	Group 2 (Neutral [Control]) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).	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. Participants formed the PK-PPS.
Measure Participants	14	14
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1753 (21.7)	1700 (29.4)

7. Secondary Outcome

Title	The Time to Reach Maximum Concentration (Tmax) for UCB1431322-000 During the Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)	Group 2 (Neutral [Control]) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).	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. Participants formed the PK-PPS.
Measure Participants	14	14
Median (Full Range) [hr]	3.500	3.500

8. Secondary Outcome

Title	The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1431322-000 During the Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)	Group 2 (Neutral [Control]) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).	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. Participants formed the PK-PPS.
Measure Participants	14	14
Geometric Mean (Geometric Coefficient of Variation) [hr*ng/mL]	11720 (21.3)	11200 (30.7)

9. Secondary Outcome

Title	The Ratio of PSL Metabolite UCB1431322-000 to PSL Based on the Area Under the Curve (AUCtau) During the Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)	Group 2 (Neutral [Control]) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).	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. Participants formed the PK-PPS.
Measure Participants	14	14
Geometric Mean (Geometric Coefficient of Variation) [ratio]	2.283 (22.4)	1.386 (48.2)

10. Secondary Outcome

Title	The Maximum Observed Plasma Concentration (Cmax) for UCB1447499-000 During the Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)	Group 2 (Neutral [Control]) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).	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. Participants formed the PK-PPS.
Measure Participants	14	14
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	380.1 (37.8)	307.2 (32.6)

11. Secondary Outcome

Title	The Time to Reach Maximum Concentration (Tmax) for UCB1447499-000 During the Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)	Group 2 (Neutral [Control]) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).	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. Participants formed the PK-PPS.
Measure Participants	14	14
Median (Full Range) [hr]	2.000	2.000

12. Secondary Outcome

Title	The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1447499-000 During the Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)	Group 2 (Neutral [Control]) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).	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. Participants formed the PK-PPS.
Measure Participants	14	14
Geometric Mean (Geometric Coefficient of Variation) [hr*ng/mL]	1854 (29.0)	1678 (28.2)

13. Secondary Outcome

Title	The Ratio of PSL Metabolite UCB1447499-000 to PSL Based on the Area Under the Curve (AUCtau)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1 (Inducers) (PK-PPS)	Group 2 (Neutral [Control]) (PK-PPS)
Arm/Group Description	Participants were on stable therapy OXC, at least 1200 mg/day, which could be used as monotherapy or adjunctive to 1 or more of LEV, LTG, or 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. Participants formed the Pharmacokinetic Per-Protocol Set (PK-PPS).	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. Participants formed the PK-PPS.
Measure Participants	14	14
Geometric Mean (Geometric Coefficient of Variation) [ratio]	0.3492 (32.8)	0.2011 (45.7)

14. Secondary Outcome

Title	Percentage of Participants With at Least One Adverse Event (AE) During the Study
Description	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)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all study participants who signed the ICF and received at least 1 dose of IMP.

Arm/Group Title	Group 1 (Inducers) (FAS)	Group 2 (Neutral [Control]) (FAS)
Arm/Group Description	Participants were on stable therapy with oxcarbazepine (OXC), at least 1200 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. Participants formed the Full Analysis Set (FAS).	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. Participants formed the FAS.
Measure Participants	16	15
Number [percentage of participants]	100 625%	100 666.7%

15. Secondary Outcome

Title	Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study
Description	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)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all study participants who signed the ICF and received at least 1 dose of IMP.

Arm/Group Title	Group 1 (Inducers) (FAS)	Group 2 (Neutral [Control]) (FAS)
Arm/Group Description	Participants were on stable therapy with oxcarbazepine (OXC), at least 1200 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. Participants formed the Full Analysis Set (FAS).	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. Participants formed the FAS.
Measure Participants	16	15
Number [percentage of participants]	0 0%	0 0%

Adverse Events

Time Frame	Treatment Emergent Adverse events (TEAEs) were collected from the Baseline Visit (Day -1) until the Safety Follow-Up Period (Day 20±1).
Adverse Event Reporting Description	Only TEAEs occurring above the reporting threshold of 5% of participants in any treatment group are included in this summary.
Arm/Group Title	Group 1 (Inducers) (FAS)		Group 2 (Neutral [Control]) (FAS)
Arm/Group Description	Participants were on stable therapy with oxcarbazepine (OXC), at least 1200 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. Participants formed the Full Analysis Set (FAS).		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. Participants formed the FAS.
All Cause Mortality
	Group 1 (Inducers) (FAS)		Group 2 (Neutral [Control]) (FAS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)
Serious Adverse Events
	Group 1 (Inducers) (FAS)		Group 2 (Neutral [Control]) (FAS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Group 1 (Inducers) (FAS)		Group 2 (Neutral [Control]) (FAS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/16 (100%)		15/15 (100%)
Cardiac disorders
Palpitations	1/16 (6.3%)	1	0/15 (0%)	0
Ear and labyrinth disorders
Vertigo	1/16 (6.3%)	1	0/15 (0%)	0
Eye disorders
Diplopia	0/16 (0%)	0	2/15 (13.3%)	2
Vision blurred	0/16 (0%)	0	1/15 (6.7%)	3
Gastrointestinal disorders
Nausea	1/16 (6.3%)	2	4/15 (26.7%)	9
Hyperchlorhydria	0/16 (0%)	0	2/15 (13.3%)	3
Vomiting	2/16 (12.5%)	2	0/15 (0%)	0
Diarrhoea	0/16 (0%)	0	1/15 (6.7%)	1
General disorders
Fatigue	0/16 (0%)	0	6/15 (40%)	18
Feeling drunk	0/16 (0%)	0	3/15 (20%)	4
Gait disturbance	1/16 (6.3%)	1	2/15 (13.3%)	2
Feeling cold	0/16 (0%)	0	2/15 (13.3%)	2
Chest pain	0/16 (0%)	0	1/15 (6.7%)	1
Chills	1/16 (6.3%)	1	0/15 (0%)	0
Crying	0/16 (0%)	0	1/15 (6.7%)	1
Feeling abnormal	0/16 (0%)	0	1/15 (6.7%)	1
Feeling jittery	0/16 (0%)	0	1/15 (6.7%)	1
Influenza like illness	0/16 (0%)	0	1/15 (6.7%)	1
Injection site haematoma	0/16 (0%)	0	1/15 (6.7%)	1
Sluggishness	0/16 (0%)	0	1/15 (6.7%)	2
Injury, poisoning and procedural complications
Procedural dizziness	0/16 (0%)	0	1/15 (6.7%)	1
Procedural nausea	0/16 (0%)	0	1/15 (6.7%)	1
Investigations
Blood calcium decreased	1/16 (6.3%)	1	1/15 (6.7%)	1
Blood sodium decreased	1/16 (6.3%)	1	1/15 (6.7%)	1
Blood calcium increased	1/16 (6.3%)	1	0/15 (0%)	0
Blood pressure increased	1/16 (6.3%)	1	0/15 (0%)	0
Blood sodium increased	1/16 (6.3%)	1	0/15 (0%)	0
Monocyte count increased	1/16 (6.3%)	1	0/15 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/16 (0%)	0	1/15 (6.7%)	1
Musculoskeletal and connective tissue disorders
Limb discomfort	0/16 (0%)	0	2/15 (13.3%)	6
Arthralgia	0/16 (0%)	0	1/15 (6.7%)	1
Back pain	1/16 (6.3%)	1	0/15 (0%)	0
Muscle spasms	0/16 (0%)	0	1/15 (6.7%)	1
Musculoskeletal chest pain	0/16 (0%)	0	1/15 (6.7%)	1
Nervous system disorders
Somnolence	12/16 (75%)	13	12/15 (80%)	53
Dizziness	9/16 (56.3%)	18	10/15 (66.7%)	62
Headache	8/16 (50%)	15	9/15 (60%)	23
Sudden onset of sleep	0/16 (0%)	0	8/15 (53.3%)	36
Amnesia	1/16 (6.3%)	2	4/15 (26.7%)	5
Disturbance in attention	0/16 (0%)	0	4/15 (26.7%)	8
Focal dyscognitive seizures	1/16 (6.3%)	4	3/15 (20%)	3
Head discomfort	0/16 (0%)	0	2/15 (13.3%)	3
Anterograde amnesia	0/16 (0%)	0	1/15 (6.7%)	1
Coordination abnormal	0/16 (0%)	0	1/15 (6.7%)	2
Dysgraphia	0/16 (0%)	0	1/15 (6.7%)	1
Facial paresis	0/16 (0%)	0	1/15 (6.7%)	1
Generalised tonic-clonic seizure	0/16 (0%)	0	1/15 (6.7%)	1
Memory impairment	0/16 (0%)	0	1/15 (6.7%)	1
Paraesthesia	0/16 (0%)	0	1/15 (6.7%)	2
Petit mal epilepsy	0/16 (0%)	0	1/15 (6.7%)	1
Slow response to stimuli	0/16 (0%)	0	1/15 (6.7%)	1
Stupor	1/16 (6.3%)	1	0/15 (0%)	0
Psychiatric disorders
Agitation	2/16 (12.5%)	2	2/15 (13.3%)	2
Insomnia	0/16 (0%)	0	4/15 (26.7%)	8
Disorientation	2/16 (12.5%)	2	1/15 (6.7%)	1
Irritability	1/16 (6.3%)	1	2/15 (13.3%)	3
Depressed mood	0/16 (0%)	0	2/15 (13.3%)	2
Abnormal dreams	0/16 (0%)	0	1/15 (6.7%)	1
Bradyphrenia	0/16 (0%)	0	1/15 (6.7%)	3
Confusional state	0/16 (0%)	0	1/15 (6.7%)	1
Euphoric mood	0/16 (0%)	0	1/15 (6.7%)	1
Hallucination, visual	0/16 (0%)	0	1/15 (6.7%)	1
Renal and urinary disorders
Polyuria	0/16 (0%)	0	1/15 (6.7%)	1
Reproductive system and breast disorders
Dysmenorrhoea	0/16 (0%)	0	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Hiccups	0/16 (0%)	0	3/15 (20%)	10
Skin and subcutaneous tissue disorders
Pruritus	1/16 (6.3%)	2	0/15 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.