A Relative Bioavailability Study of Staccato Alprazolam Versus Oral Alprazolam in Healthy Study Participants

An Open-Label, Randomized, Single-Dose, 2-Way Crossover Study to Evaluate The Relative Bioavailability of Staccato Alprazolam Compared to Oral Alprazolam in Healthy Study Participants

The purpose of the study is to evaluate the relative bioavailability of alprazolam in plasma following a single dose of Staccato alprazolam compared to a single dose of oral alprazolam under fasted conditions

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Staccato alprazolam; Drug: Oral alprazolam

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Up0104 1001

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring, at the Screening Visit or on Day -1 of the first Treatment Period
• Participant has a body weight of at least 45 kg (female) and 50 kg (male) and body mass index (BMI) within the range 18 to 35 kg/m^2 (inclusive) at the Screening Visit or on Day -1 of the first Treatment Period
• Participants may be male or female:

A male participant must agree to use contraception as detailed in the protocol during the Treatment Periods and for at least 7 days after the second Investigational Medicinal Product (IMP) administration and must 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 in the protocol OR A WOCBP who agrees to follow the contraceptive guidance in the protocol during the Treatment Periods and for at least 30 days after the second IMP administration

Exclusion Criteria:

• 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
• Participant has a history or present condition of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, neurological, 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 IMP; or interfering with the interpretation of data
• Participant has abnormal blood pressure (BP) or heart rate (HR) at the Screening Visit or on Day -1 of the first Treatment Period (as stated in the protocol). Study participants must have BP and HR within normal range in the supine position after 5 minutes of rest (systolic BP [SBP]: 90 mmHg to 140 mmHg, diastolic BP [DBP]: 50 mmHg to 90 mmHg, HR: 50 beats per minute to 100 beats per minute (bpm). In case of an out-of-range result, 1 repeat will be allowed. If the readings are out of range again, the study participant will not be included
• Participant has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt) or has had suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the "Screening/Baseline" version of the Columbia Suicide Severity Rating Scale (C-SSRS) at the Screening Visit
• Participant has had a positive test for Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) or clinical signs/symptoms consistent with coronavirus disease 2019 (COVID-19) such as fever, persistent cough, shortness of breath, fatigue, and loss or change to senses of smell or taste during the 4 weeks prior to the Screening Visit or Day -1 of the first Treatment Period
• Participant has a condition for which oral alprazolam is contraindicated (eg, myasthenia gravis, severe respiratory insufficiency, sleep apnea syndrome, and severe hepatic insufficiency)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence AB; Study participants randomized into this arm will receive single dose of Staccato alprazolam followed by single dose of oral alprazolam at pre-specified time points in the sequence AB.	Drug: Staccato alprazolam; Study participants will receive single dose of Staccato alprazolam by inhalation at pre-specified time points.; Other Names: UCB7538; Drug: Oral alprazolam; Study participants will receive single dose of oral alprazolam at pre-specified time points.; Other Names: Xanax
Experimental: Treatment Sequence BA; Study participants randomized into this arm will receive single dose of oral alprazolam followed by single dose of Staccato alprazolam at pre-specified time points in the sequence BA.	Drug: Staccato alprazolam; Study participants will receive single dose of Staccato alprazolam by inhalation at pre-specified time points.; Other Names: UCB7538; Drug: Oral alprazolam; Study participants will receive single dose of oral alprazolam at pre-specified time points.; Other Names: Xanax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration-time curve from time 0 to infinity (AUC) of alprazolam	AUC = Area under the plasma concentration-time curve from time zero to infinity	Plasma samples will be collected from Baseline (Day 1 predose) at predefined time points (up to Day 3)
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC(0-t)) of alprazolam	AUC(0-t) = Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration	Plasma samples will be collected from Baseline (Day 1 predose) at predefined time points (up to Day 3)
Maximum plasma concentration (Cmax) of alprazolam	Cmax = Maximum plasma concentration	Plasma samples will be collected from Baseline (Day 1 predose) at predefined time points (up to Day 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of study participants with treatment-emergent adverse events (TEAEs)	An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication.	From Baseline (Day 1) of Treatment Period 1 to the end of Safety Follow-Up (up to 25 days)
Percentage of study participants with serious treatment-emergent adverse events (serious TEAEs)	A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death Is life-threatening Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent disability/incapacity Is a congenital anomaly/birth defect Important medical events referred to in the Protocol.	From Baseline (Day 1) of Treatment Period 1 to the end of Safety Follow-Up (up to 25 days)

Collaborators and Investigators

• Sponsor: UCB Biopharma SRL
• Investigators: Study Director: UCB Cares, 001 844 599 2273 (UCB)

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2022
• Primary Completion (Actual): February 24, 2023
• Study Completion (Actual): February 24, 2023

Study Registration Dates

• First Submitted: November 15, 2022
• First Submitted That Met QC Criteria: November 15, 2022
• First Posted (Actual): November 23, 2022

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Phase 1; Bioavailability; Healthy participants; Staccato alprazolam
• Additional Relevant MeSH Terms: 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: UP0104

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.: Yes