A Study to Test the Pharmacodynamic, Pharmacokinetic, Safety, and Tolerability of Padsevonil in Healthy Study Participants Receiving Either Ethanol or Cannabidiol

NCT04039919 | Terminated Phase 1 Results

• 2 other identifiers: UP00712019-000703-32
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the pharmacodynamic (PD) interaction between steady-steady treatment with padsevonil (PSL) and Ethanol and the pharmacokinetic (PK) interaction between stead-state treatment with PSL and cannabidiol (CBD).

Conditions

Healthy Participants

Keywords

Ethanol; Cannabidiol; Padsevonil

Outcome Measures

Primary Outcomes (6)

• Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A

  Smooth pursuit to assess eye movement coordination and attention to evaluate the ethanol effect. The average percentage of smooth pursuit for all stimulus frequencies was used as a parameter. Participants received either ethanol or placebo on Day 1 of Period 1 or on Day 3 of Period 2. Therefore, the results were summarized by treatment.

  Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 1 of Period 1 or Day 3 of Period 2

• Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A

  Smooth pursuit to assess eye movement coordination and attention to evaluate the ethanol effect. The average percentage of smooth pursuit for all stimulus frequencies was used as a parameter. Participants received either ethanol or placebo on Day 5 of Period 4 or Day 7 of Period 5. Therefore, the results were summarized by treatment.

  Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 5 of Period 4 or Day 7 of Period 5

• Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part B

  Cmax is maximum observed plasma concentration at steady state of padsevonil.

  Predose up to 12 hours postdose

• Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Cannabidiol During Part B

  Cmax is maximum observed plasma concentration at steady state of CBD.

  Predose up to 12 hours postdose

• Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part B

  AUCtau is the area under the curve over a dosing interval of padsevonil.

  Predose up to 12 hours post dose

• Area Under the Curve Over a Dosing Interval (AUCtau) of Cannabidiol During Part B

  AUCtau is the area under the curve over a dosing interval of CBD.

  Predose up to 12 hours postdose

Secondary Outcomes (26)

• Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A

  -0.4, -0.3, -0.2, -0.16, -0.08, Predose, 0.16, 0.3, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7 and 8 hours postdose on Day 1 of Period 1 or on Day 3 of Period 2

• Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A

  -0.4, -0.3, -0.2, -0.16, -0.08, Predose, 0.16, 0.3, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7 and 8 hours postdose on Day 5 of Period 4 or Day 7 of Period 5

• Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part A

  Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose on Day 5

• Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part A

  Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose on Day 5

• Half-life (t1/2) of Padsevonil During Part B

  Predose up to 12 hours postdose

Study Arms (6)

Part A: Padsevonil and Ethanol

EXPERIMENTAL

Subjects will be randomized to receive Padsevonil and Ethanol.

Drug: Padsevonil

Part A: Padsevonil and Ethanol-Placebo

PLACEBO COMPARATOR

Subjects will be randomized to receive Padsevonil and Ethanol-Placebo.

Drug: Padsevonil

Part A: Ethanol and Ethanol-Placebo

NO INTERVENTION

Subjects will be randomized to receive Ethanol and Ethanol-Placebo.

Part A: Ethanol-Placebo and Ethanol

NO INTERVENTION

Subjects will be randomized to receive Ethanol and Ethanol-Placebo.

Part B: Padsevonil and Cannabidiol

EXPERIMENTAL

Subjects will be randomized to receive Padsevonil and Cannabidiol.

Drug: Padsevonil

Part B: Padsevonil-Placebo and Cannabidiol

PLACEBO COMPARATOR

Subjects will be randomized to receive Padsevonil-Placebo and Cannabidiol.

Drug: Placebo (PSL)

Interventions

Padsevonil DRUG

Padsevonil will be administered in predefined dosages.

Part A: Padsevonil and Ethanol; Part A: Padsevonil and Ethanol-Placebo; Part B: Padsevonil and Cannabidiol

Placebo (PSL) DRUG

Placebo will be provided matching Padsevonil to maintain the blinding.

Part B: Padsevonil-Placebo and Cannabidiol

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
• Participant must have previous experience with alcohol consumption and, therefore, must be familiar with the effects and able to tolerate social amounts of alcohol
• Participant has a body weight of at least 50 kg (males) or 45 kg (females) and body mass index (BMI) within the range 18 to 30 kg/m2 (inclusive)
• Participants are male or female:
• A male participant must agree to use contraception as detailed in the protocol 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
• 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) as defined n the protocol OR
• A WOCBP who agrees to follow the contraceptive guidance in the protocol during the Treatment Period and for at least 90 days after the last dose of study treatment

You may not qualify if:

• Participant has history or presence 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
• Participant has a history of chronic alcohol or drug abuse within the previous 6 months or the presence of drug or alcohol dependency at Screening or Day -1 or tests positive for alcohol and/or drugs at Screening or Day -1
• Participant has a known hypersensitivity to any components of the study medication or comparative drugs (and/or an investigational device) as stated in this protocol
• Participant has a history of unexplained syncope or a family history of sudden death due to long QT syndrome
• Participant has 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
• Participant has past or intended use of over-the-counter or prescription medication including herbal medications within 2 weeks or 5 half-lives prior to dosing
• Participant has used hepatic enzyme-inducing drugs within 2 months prior to dosing
• Participant has alanine transaminase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) \>1.0x upper limit of normal (ULN)
• Participant has current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Participant has any clinically relevant electrocardiogram (ECG) finding at the Screening Visit or at Baseline
• Participant has the presence of hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to dosing
• Participant has a positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention
• Participant has a positive human immunodeficiency virus (HIV) antibody test

Sponsors & Collaborators

• UCB Biopharma S.P.R.L.: lead

Study Sites (1)

Up0071 001

Leiden, Netherlands

Location

MeSH Terms

Interventions

padsevonil

Limitations and Caveats

The study was terminated because the decision was made to terminate the PSL development program in focal-onset seizures on 22 May 2020.

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

+1844 599

Study Officials

• UCB Cares

  001 844 599 2273 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2019
• First Posted: July 31, 2019
• Study Start: July 17, 2019
• Primary Completion: May 22, 2020
• Study Completion: May 22, 2020
• Last Updated: June 18, 2021
• Results First Posted: June 18, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)