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 )

Tracking Information

• First Submitted Date: November 15, 2022
• First Posted Date: November 23, 2022
• Last Update Posted Date: March 18, 2024
• Actual Study Start Date: December 28, 2022
• Actual Primary Completion Date: February 24, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 28, 2022)

• 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

Original Primary Outcome Measures (submitted: November 15, 2022)

• Area under the plasma concentration-time curve from time 0 to infinity (AUC) of alprazolam [ Time Frame: Plasma samples will be collected from Day 1 at 30 minutes (min) predose, then postdose at 2 min, 5 min, 10 min, 20 min, 30 min, 45 min, 1 hour (hr), 1 hr 30 min, 2 hours (hrs), 4 hrs, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, 60 hrs, and 72 hrs. ]
  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 Day 1 at 30 minutes (min) predose, then postdose at 2 min, 5 min, 10 min, 20 min, 30 min, 45 min, 1 hour (hr), 1 hr 30 min, 2 hours (hrs), 4 hrs, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, 60 hrs, and 72 hrs. ]
  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 Day 1 at 30 minutes (min) predose, then postdose at 2 min, 5 min, 10 min, 20 min, 30 min, 45 min, 1 hour (hr), 1 hr 30 min, 2 hours (hrs), 4 hrs, 6 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, 60 hrs, and 72 hrs. ]
  Cmax = Maximum plasma concentration

Current Secondary Outcome Measures (submitted: November 15, 2022)

• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Relative Bioavailability Study of Staccato Alprazolam Versus Oral Alprazolam in Healthy Study Participants
• 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
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Healthy Participants

Intervention

• 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

Study Arms

• 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.
  Interventions:

  • Drug: Staccato alprazolam
  • Drug: Oral alprazolam
• 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.
  Interventions:

  • Drug: Staccato alprazolam
  • Drug: Oral alprazolam

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 24, 2023): 21
• Original Estimated Enrollment (submitted: November 15, 2022): 20
• Actual Study Completion Date: February 24, 2023
• Actual Primary Completion Date: February 24, 2023 (Final data collection date for primary outcome measure)

Eligibility 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05626439
• Other Study ID Numbers: UP0104
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

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.

• Current Responsible Party: UCB Pharma ( UCB Biopharma SRL )
• Original Responsible Party: Same as current
• Current Study Sponsor: UCB Biopharma SRL
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: UCB Pharma
• Verification Date: March 2024