A Study to Test the Blood Concentration of 4 Padsevonil Product Variants and the Effect of Food on Padsevonil

An Open-Label, Randomized, Single-Dose, 2-Part Crossover Study in Healthy Study Participants to Evaluate the Relative Bioavailability of 4 Padsevonil Product Variants and the Effect of Food on Padsevonil

The purpose of the study in Part 1, is to evaluate (under fasted conditions) the plasma pharmacokinetics (PK) of padsevonil (PSL) using 4 PSL product variants against a PSL reference tablet and in Part 2, to evaluate the PK of PSL using a PSL reference tablet under fed and fasted conditions at 200 mg and 400 mg.

Study Overview

• Status: Withdrawn
• Conditions: Epilepsy; Healthy Participants
• Intervention / Treatment: Drug: Padsevonil type 1 Tablet 200 mg; Drug: Padsevonil type 2 Tablet; Drug: Padsevonil type 3 Tablet; Drug: Padsevonil type 4 Tablet; Drug: Padsevonil type 5 Tablet

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant must be 18 to 55 years of age, inclusive, at the time of signing the informed consent form (ICF)
• Study participants must be overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
• Study participants must have a body weight of at least 50 kg for males and 45 kg for females and body mass index within the range 18 to 35 kg/m2 (inclusive)

• Study participants who are male or female:

  1. A male participant must agree to use contraception during the treatment period and for at least 7 days after the last dose of study treatment 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 the treatment period and for at least 30 days (or 5 terminal half-lives) after the last dose of study medication

Exclusion Criteria:

• Study participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study or a history of schizophrenia, or other psychotic disorder, bipolar disorder, or severe unipolar depression. The presence of potential psychiatric exclusion criteria will be determined based on the psychiatric history collected at Screening
• Study participant has a history or presence of/significant history of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data
• Study participant has a history or present condition of respiratory or cardiovascular disorders, (eg, cardiac insufficiency, coronary heart disease, hypertension, arrhythmia, tachyarrhythmia, or myocardial infarction)
• Study participant has had lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years
• Study participant has used hepatic enzyme-inducing drugs (eg, glucocorticoids, phenobarbital, isoniazid, phenytoin, rifampicin, etc) within 2 months prior to the first dose of study medication. In case of uncertainty, the Medical Monitor should be consulted
• Study participant has participated in another study of an investigational study medication (and/or an investigational device) within the previous 60 days before Screening (or 5 half-lives, whichever is longer) or is currently participating in another study of an investigational study medication (and/or an investigational device)
• Study participant has made a blood donation or has had a comparable blood loss (>400 mL) within the last 3 months prior to the Screening Visit or has made plasma donation within last month prior to the Screening Visit
• Study participant smokes more than 5 cigarettes per day (or equivalent) or has done so within 6 months prior to the Screening Visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Type 1 tablet - part 1; Subjects will receive a single dose of padsevonil Type 1 tablet in the period defined by the pre-specified sequence they were randomized on to.	Drug: Padsevonil type 1 Tablet 200 mg; Pharmaceutical form: Film-coated tablet; Route of administration: Oral use Subjects will receive a padsevonil type 1 tablet in a pre-specified sequence during the Treatment Period.
EXPERIMENTAL: Type 2 tablet - part 1; Subjects will receive a single dose of padsevonil Type 2 tablet in the period defined by the pre-specified sequence they were randomized on to.	Drug: Padsevonil type 2 Tablet; Pharmaceutical form: Film-coated tablet; Route of administration: Oral use Subjects will receive a padsevonil type 2 tablet in a pre-specified sequence during the Treatment Period
EXPERIMENTAL: Type 3 tablet - part 1; Subjects will receive a single dose of padsevonil Type 3 tablet in the period defined by the pre-specified sequence they were randomized on to.	Drug: Padsevonil type 3 Tablet; Pharmaceutical form: Film-coated tablet; Route of administration: Oral use Subjects will receive a padsevonil type 3 tablet in a pre-specified sequence during the Treatment Period.
EXPERIMENTAL: Type 4 tablet - part 1; Subjects will receive a single dose of padsevonil Type 4 tablet in the period defined by the pre-specified sequence they were randomized on to.	Drug: Padsevonil type 4 Tablet; Pharmaceutical form: Film-coated tablet; Route of administration: Oral use Subjects will receive a padsevonil type 4 tablet in a pre-specified sequence during the Treatment Period.
EXPERIMENTAL: Type 5 tablet - part 1; Subjects will receive a single dose of padsevonil Type 5 tablet in the period defined by the pre-specified sequence they were randomized on to.	Drug: Padsevonil type 5 Tablet; Pharmaceutical form: Film-coated tablet; Route of administration: Oral use Subjects will receive a padsevonil type 5 tablet in a pre-specified sequence during the Treatment Period.
ACTIVE_COMPARATOR: Type 1 tablet - part 2 (2 x 200 mg fasted); Subjects will receive a single 2 x 200 mg dose of padsevonil Type 1 tablet under fasting conditions in the period defined by the pre-specified sequence they were randomized on to.	Drug: Padsevonil type 1 Tablet 200 mg; Pharmaceutical form: Film-coated tablet; Route of administration: Oral use Subjects will receive a padsevonil type 1 tablet in a pre-specified sequence during the Treatment Period.
ACTIVE_COMPARATOR: Type 1 tablet - part 2 (2 x 200 mg fed); Subjects will receive a single 2 x 200 mg dose of padsevonil Type 1 tablet under fed conditions in the period defined by the pre-specified sequence they were randomized on to.	Drug: Padsevonil type 1 Tablet 200 mg; Pharmaceutical form: Film-coated tablet; Route of administration: Oral use Subjects will receive a padsevonil type 1 tablet in a pre-specified sequence during the Treatment Period.
ACTIVE_COMPARATOR: Type 1 tablet - part 2 (200 mg fasted); Subjects will receive a single 200 mg dose of padsevonil Type 1 tablet under fasting conditions in the period defined by the pre-specified sequence they were randomized on to.	Drug: Padsevonil type 1 Tablet 200 mg; Pharmaceutical form: Film-coated tablet; Route of administration: Oral use Subjects will receive a padsevonil type 1 tablet in a pre-specified sequence during the Treatment Period.
ACTIVE_COMPARATOR: Type 1 tablet - part 2 (200 mg fed); Subjects will receive a single 200 mg dose of padsevonil Type 1 tablet under fed conditions in the period defined by the pre-specified sequence they were randomized on to.	Drug: Padsevonil type 1 Tablet 200 mg; Pharmaceutical form: Film-coated tablet; Route of administration: Oral use Subjects will receive a padsevonil type 1 tablet in a pre-specified sequence during the Treatment Period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-t of padsevonil type 1 tablets during part 1	AUC(0-t): Area under the plasma concentration-time curve from time zero to time t	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
AUC0-t of padsevonil type 2 tablets during part 1	AUC(0-t): Area under the plasma concentration-time curve from time zero to time t	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
AUC0-t of padsevonil type 3 tablets during part 1	AUC(0-t): Area under the plasma concentration-time curve from time zero to time t	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
AUC0-t of padsevonil type 4 tablets during part 1	AUC(0-t): Area under the plasma concentration-time curve from time zero to time t	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
AUC0-t of padsevonil type 5 tablets during part 1	AUC(0-t): Area under the plasma concentration-time curve from time zero to time t	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
AUC0-t of padsevonil type 1 tablets (2x200 mg, fasted) during part 2	AUC(0-t): Area under the plasma concentration-time curve from time zero to time t	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2.
AUC0-t of padsevonil type 1 tablets (2x200 mg, fed) during part 2	AUC(0-t): Area under the plasma concentration-time curve from time zero to time t	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2.
AUC0-t of padsevonil type 1 tablets (200 mg, fasted) during part 2	AUC(0-t): Area under the plasma concentration-time curve from time zero to time t	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2.
AUC0-t of padsevonil type 1 tablets (200 mg, fed) during part 2	AUC(0-t): Area under the plasma concentration-time curve from time zero to time t	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2.
AUC of padsevonil type 1 tablets during part 1	AUC: Area under the concentration-time curve from time 0 to infinity	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
AUC of padsevonil type 2 tablets during part 1	AUC: Area under the concentration-time curve from time 0 to infinity	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
AUC of padsevonil type 3 tablets during part 1	AUC: Area under the concentration-time curve from time 0 to infinity	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
AUC of padsevonil type 4 tablets during part 1	AUC: Area under the concentration-time curve from time 0 to infinity	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
AUC of padsevonil type 5 tablets during part 1	AUC: Area under the concentration-time curve from time 0 to infinity	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
AUC of padsevonil type 1 tablets (400 mg, fasted) during part 2	AUC: Area under the concentration-time curve from time 0 to infinity	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2.
AUC of padsevonil type 1 tablets (400 mg, fed) during part 2	AUC: Area under the concentration-time curve from time 0 to infinity	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2.
AUC of padsevonil type 1 tablets (200 mg, fasted) during part 2	AUC: Area under the concentration-time curve from time 0 to infinity	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2.
AUC of padsevonil type 1 tablets (200 mg, fed) during part 2	AUC: Area under the concentration-time curve from time 0 to infinity	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2.
Cmax of padsevonil type 1 tablets during part 1	Cmax: Maximum observed plasma concentration	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
Cmax of padsevonil type 2 tablets during part 1	Cmax: Maximum observed plasma concentration	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
Cmax of padsevonil type 3 tablets during part 1	Cmax: Maximum observed plasma concentration	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
Cmax of padsevonil type 4 tablets during part 1	Cmax: Maximum observed plasma concentration	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
Cmax of padsevonil type 5 tablets during part 1	Cmax: Maximum observed plasma concentration	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1.
Cmax of padsevonil type 1 tablets (400 mg, fasted) during part 2	Cmax: Maximum observed plasma concentration	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2.
Cmax of padsevonil type 1 tablets (400 mg, fed) during part 2	Cmax: Maximum observed plasma concentration	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2.
Cmax of padsevonil type 1 tablets (200 mg, fasted) during part 2	Cmax: Maximum observed plasma concentration	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2.
Cmax of padsevonil type 1 tablets (200 mg, fed) during part 2	Cmax: Maximum observed plasma concentration	Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (TEAEs)	An Adverse Event 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.	From Baseline up to Day 35
Incidence of 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	From Baseline up to Day 35

Collaborators and Investigators

• Sponsor: UCB Biopharma SRL

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 24, 2020
• Primary Completion (ACTUAL): May 22, 2020
• Study Completion (ACTUAL): May 22, 2020

Study Registration Dates

• First Submitted: February 21, 2020
• First Submitted That Met QC Criteria: February 21, 2020
• First Posted (ACTUAL): February 25, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 22, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Food effect; Phase 1; Bioavailability; Padsevonil
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: UP0081

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to the small sample size in this trial, Individual Patient Data cannot be adequately anonymized and there is a reasonable likelihood that individual participants could be re-identified. For this reason, data from this trial cannot be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No