A Study to Assess the Pharmacokinetics (PK) and Safety of Staccato Alprazolam in Adolescent Study Participants With Epilepsy

A Multicenter, Open-Label Study to Evaluate the Pharmacokinetics, Tolerability, and Safety of a Single Dose of Staccato Alprazolam in Adolescent Study Participants With Epilepsy

The purpose of the study is to assess the pharmacokinetics (PK), tolerability, and safety of Staccato alprazolam in adolescent study participants with epilepsy following single-dose administration.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Alprazolam

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Up0100 102
  • Florida
    • Orlando, Florida, United States, 32806
      • Up0100 110
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Up0100 103
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Up0100 101
  • New York
    • Rochester, New York, United States, 14642
      • Up0100 108
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Up0100 106
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Up0100 105
  • Washington
    • Tacoma, Washington, United States, 98405
      • Up0100 107

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant must be 12 to 17 years of age inclusive, at the time of signing the Informed Consent form (ICF) and the Assent form
• Participant has an established diagnosis of focal, generalized, or focal and generalized epilepsy
• Participant is in good general health as determined by medical evaluation including medical history and physical examination
• Participants with a body weight ≥29 kg and body mass index (BMI) within the range 14 to 32 kg/m^2 (inclusive)
• A male participant must agree to use contraception
• A female participant is eligible to participate if she is not pregnant
• Participant is capable of and provides assent, and the study participant's parent/legal representative provides signed informed consent for minor study participants, which includes compliance with the requirements and restrictions listed in the ICF, Assent form, and in this protocol
• Participant has a lifetime history of never smoking >5 cigarettes/day, and a current history (for at least 6 months prior to Screening Visit) of not smoking at all (including e-cigarette and vaping products)
• Participant has forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) >80% predicted at Screening. In case of an out-of-range result, 1 repeat test will be allowed. If the readings are out-of-range again, the study participant will be excluded
• Participant is willing and able to be confined to a clinical research facility for up to 36 hours (including 1 overnight stay) and comply with the study schedule and study requirements.

Note: If there are no clinical contraindications, as per Investigator's judgment, study participants may leave the clinical research facility after the 6-hour postdose assessments and return to the clinic on Day 2 for the 24-hour and 36-hour postdose assessments

• Participant is currently taking at least 1 background antiepileptic drug (AED)
• Participant is able to actuate the training device during Screening, according to Instructions for Use

Exclusion Criteria:

• Participant has history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, neurological, hematological, cerebrovascular, or other major disorders capable of significantly altering the absorption, metabolism, or elimination of Investigational Medicinal Product (IMP); constituting a risk when taking the study intervention; or interfering with the interpretation of data in the opinion of the Investigator
• Participant has a known hypersensitivity to any components of the IMP or comparative drugs (and/or an investigational device) as stated in the protocol
• Participant has severe chronic cardio-respiratory disease
• Participant has history of acute narrow angle glaucoma, hydrocephalus, or Myasthenia Gravis
• Participant has history or has current airway disease such asthma, cystic fibrosis, or chronic obstructive pulmonary disease
• Participant has any acute respiratory signs/symptoms (ie, wheezing) and active acute respiratory infection (or within 1 week of dosing) with exception of symptoms of mild rhinitis
• Participant has a known hypersensitivity to albuterol or similar short-acting beta2-agonist (SABA) that may be used as rescue medication administered in response to potential bronchospasm
• Participant is taking strong liver inducing agents (eg, phenytoin, phenobarbital, carbamazepine, and primidone) or strong Cytochrome P450 3A4 (CYP3A4) inhibitors
• Participant has a SpO2 measured by pulse oximetry <95% for >30 seconds during the Screening Visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Staccato alprazolam; The study participants will receive a single dose of Staccato alprazolam.	Drug: Alprazolam; Pharmaceutical form: Inhalation powder.; Study participants will receive Staccato alprazolam at prespecified time-points.; Other Names: UCB7538

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) following single inhaled dose of Staccato alprazolam	Cmax = Maximum plasma concentration.	Plasma samples will be taken on Day 1 of the Treatment Period, predose and then following administration of Investigational Medicinal Product (IMP) at 2 minutes, 10 minutes, 30 minutes, 1 hour, 2 hours, 6 hours, 24 hours, and 36 hours postdose.
Area under the plasma concentration-time curve from zero to the last quantifiable concentration (AUC(0-t)) following single inhaled dose of Staccato alprazolam	AUC(0-t) = Area under the plasma concentration-time curve from zero to the last quantifiable concentration.	Plasma samples will be taken on Day 1 of the Treatment Period, predose and then following administration of Investigational Medicinal Product (IMP) at 2 minutes, 10 minutes, 30 minutes, 1 hour, 2 hours, 6 hours, 24 hours, and 36 hours postdose.
Area under the plasma concentration-time curve from time 0 to infinity (AUC) following single inhaled dose of Staccato alprazolam	AUC = Area under the plasma concentration-time curve from time 0 to infinity.	Plasma samples will be taken on Day 1 of the Treatment Period, predose and then following administration of Investigational Medicinal Product (IMP) at 2 minutes, 10 minutes, 30 minutes, 1 hour, 2 hours, 6 hours, 24 hours, and 36 hours postdose.
Apparent total body clearance (CL/F) following single inhaled dose of Staccato alprazolam	CL/F = Apparent total body clearance.	Plasma samples will be taken on Day 1 of the Treatment Period, predose and then following administration of Investigational Medicinal Product (IMP) at 2 minutes, 10 minutes, 30 minutes, 1 hour, 2 hours, 6 hours, 24 hours, and 36 hours postdose.
Percentage of participants with treatment-emergent adverse event (TEAEs)	An Adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant temporally associated with the use of IMP, whether or not considered related to the IMP.	From baseline (Day 1) till end of Safety Follow-up (up to Day 9)
Percentage of participants with serious treatment-emergent adverse event (serious TEAEs)	A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: a. Results in death c. Requires inpatient hospitalization or prolongation of existing hospitalization d. Results in persistent disability/incapacity e. Is a congenital anomaly/birth defect f. Important medical events.	From baseline (Day 1) till end of Safety Follow-up (up to Day 9)

Collaborators and Investigators

• Sponsor: UCB Biopharma SRL

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2021
• Primary Completion (Actual): April 5, 2022
• Study Completion (Actual): April 5, 2022

Study Registration Dates

• First Submitted: April 22, 2021
• First Submitted That Met QC Criteria: April 22, 2021
• First Posted (Actual): April 23, 2021

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Adolescents; Epilepsy; Phase 1; Staccato alprazolam; Alprazolam; STAP-001
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Alprazolam
• Other Study ID Numbers: UP0100

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, IPD cannot be adequately anonymized i.e., 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