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

Epilepsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04857307
• Other study ID #: UP0100
• Status: Completed
• Phase: Phase 1
• Start date: April 28, 2021
• Est. completion date: April 5, 2022

Study information

• Verified date: June 2022
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: April 5, 2022
• Est. primary completion date: April 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• Alprazolam
Pharmaceutical form: Inhalation powder. Study participants will receive Staccato alprazolam at prespecified time-points.

Locations

Country	Name	City	State
United States	Up0100 101	Bethesda	Maryland
United States	Up0100 106	Cincinnati	Ohio
United States	Up0100 103	Honolulu	Hawaii
United States	Up0100 102	Little Rock	Arkansas
United States	Up0100 105	Memphis	Tennessee
United States	Up0100 110	Orlando	Florida
United States	Up0100 108	Rochester	New York
United States	Up0100 107	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Country where clinical trial is conducted

United States, 

Outcome

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