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

Overview

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

Full Title of Study: “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”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Crossover Assignment
  • Primary Purpose: Basic Science
  • Masking: None (Open Label)
• Study Primary Completion Date: February 24, 2023

Interventions

• Drug: Staccato alprazolam
  • Study participants will receive single dose of Staccato alprazolam by inhalation at pre-specified time points.
• Drug: Oral alprazolam
  • Study participants will receive single dose of oral alprazolam at pre-specified time points.

Arms, Groups and Cohorts

• 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.
• 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.

Clinical Trial Outcome Measures

Primary Measures

• 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
• 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
• 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 Measures

• 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.
• 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.

Participating in This Clinical Trial

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)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

• Lead Sponsor
  • UCB Biopharma SRL
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • UCB Cares, Study Director, 001 844 599 2273 (UCB)