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

Epilepsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04283136
• Other study ID #: UP0081
• Status: Withdrawn
• Phase: Phase 1
• Start date: February 24, 2020
• Est. completion date: May 22, 2020

Study information

• Verified date: June 2020
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 22, 2020
• Est. primary completion date: May 22, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Epilepsy
• Healthy Participants

Intervention

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.
• 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
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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	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
Secondary	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