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

• ClinicalTrials.gov Identifier: NCT05626439
• Recruitment Status: Completed
• First Posted: November 23, 2022
• Last Update Posted: March 18, 2024
• Sponsor: UCB Biopharma SRL
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma SRL )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy Participants	Drug: Staccato alprazolam; Drug: Oral alprazolam	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: December 28, 2022
• Actual Primary Completion Date: February 24, 2023
• Actual Study Completion Date: February 24, 2023

Arms and Interventions

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 Name: UCB7538; Drug: Oral alprazolam; Study participants will receive single dose of oral alprazolam at pre-specified time points.; Other Name: 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 Name: UCB7538; Drug: Oral alprazolam; Study participants will receive single dose of oral alprazolam at pre-specified time points.; Other Name: Xanax

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Percentage of study participants with treatment-emergent adverse events (TEAEs) [ Time Frame: From Baseline (Day 1) of Treatment Period 1 to the end of Safety Follow-Up (up to 25 days) ]
   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.
2. Percentage of study participants with serious treatment-emergent adverse events (serious TEAEs) [ Time Frame: From Baseline (Day 1) of Treatment Period 1 to the end of Safety Follow-Up (up to 25 days) ]

   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.

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

United States, Maryland

Up0104 1001

Baltimore, Maryland, United States, 21225

Sponsors and Collaborators

UCB Biopharma SRL

Investigators

• Study Director: UCB Cares; 001 844 599 2273 (UCB)

More Information

• Responsible Party: UCB Biopharma SRL
• ClinicalTrials.gov Identifier: NCT05626439
• Other Study ID Numbers: UP0104
• First Posted: November 23, 2022
• Last Update Posted: March 18, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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.

• 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

Keywords provided by UCB Pharma ( UCB Biopharma SRL ):

Healthy participants; Bioavailability; Phase 1; Staccato alprazolam

Additional relevant MeSH terms:

Alprazolam; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action