A Study to Assess the Time to Onset of Action of Staccato Alprazolam Versus Midazolam and Diazepam in Healthy Participants

Phase 1

Not yet recruiting

• Conditions: Healthy Participants
• Interventions: Drug: Staccato Alprazolam; Drug: Midazolam; Drug: Diazepam

• Registration Number: NCT07020988
• Lead Sponsor: UCB Biopharma SRL

Brief Summary

The purpose of this study is to estimate the difference in the time to onset of action between Staccato alprazolam and intravenous (iv) midazolam using changes in power in the combined spindle and β1 frequency bands in the qEEG (quantitative electroencephalogram).

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-05
• Study First Submitted QC: 2025-06-05
• Last Update Submitted: 2025-06-05
• Study First Posted: 2025-06-13
• Last Update Posted: 2025-06-13
• Study Start: 2025-07-31
• Primary Completion: 2026-01-29
• Study Completion: 2026-01-29

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Participant must be 20 years to 55 years of age, inclusive, at the time of signing the ICF.
• Participant is overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring, at the Screening Visit and on Day -1 of the single Intervention Period for the Pilot Part or on Day -1 of the first Intervention Period for the Main Part of the study.
• Participant has a bodyweight of at least 45 kilograms (kg) (female) and 50 kg (male) and a body mass index within the range of 18 Kilograms per meter square (Kg/m2) to 30 kg/m2 (inclusive)
• Participant has given informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in protocol.

Exclusion Criteria

• Participant has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the participant's ability to participate in this study.
• Participant has a history of chronic alcohol or drug abuse, as defined in the most recent version of the Diagnostic and Statistical Manual of Mental Disorders, within 6 months prior to the Screening Visit.
• Participant has a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, neurological, cerebrovascular, or other major disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
• Participant has a history of or has been diagnosed with epilepsy or epileptic seizures.
• Participant has abnormal EEG findings at Screening including background slowing (<8Hz), focal slowing (focal δ-activity), or epileptiform discharges.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Main Part-Group 2: Treatment Sequence CA	Staccato Alprazolam	Study participants randomized in Group 2 will receive Treatment C: Nasal Diazepam on Day 1 of the Intervention Period 1 followed by Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 2.
Main Part-Group 2: Treatment Sequence CA	Diazepam	Study participants randomized in Group 2 will receive Treatment C: Nasal Diazepam on Day 1 of the Intervention Period 1 followed by Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 2.
Pilot Part	Midazolam	Study participants who successfully completed the Screening Period will receive single dose of Intravenous (IV) midazolam on Day 1 of the Intervention Period.
Main Part-Group 1: Treatment Sequence AB	Staccato Alprazolam	Study participants randomized in Group 1 will receive Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 1 followed by Treatment B: IV Midazolam on Day 1 of the Intervention Period 2.
Main Part-Group 1: Treatment Sequence AB	Midazolam	Study participants randomized in Group 1 will receive Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 1 followed by Treatment B: IV Midazolam on Day 1 of the Intervention Period 2.
Main Part-Group 1: Treatment Sequence BA	Staccato Alprazolam	Study participants randomized in Group 1 will receive Treatment B: IV Midazolam on Day 1 of the Intervention Period 1 followed by Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 2.
Main Part-Group 1: Treatment Sequence BA	Midazolam	Study participants randomized in Group 1 will receive Treatment B: IV Midazolam on Day 1 of the Intervention Period 1 followed by Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 2.
Main Part-Group 2: Treatment Sequence AC	Staccato Alprazolam	Study participants randomized in Group 2 will receive Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 1 followed by Treatment C: Nasal Diazepam on Day 1 of the Intervention Period 2.
Main Part-Group 2: Treatment Sequence AC	Diazepam	Study participants randomized in Group 2 will receive Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 1 followed by Treatment C: Nasal Diazepam on Day 1 of the Intervention Period 2.

Primary Outcome Measures

Name	Time	Method
Time to reach a z-score of absolute power >2 and maintained for at least 60 seconds in the combined spindle and β1 frequency bands within the first 60 minutes of study intervention administration of Staccato alprazolam in Group 1	Within the first 60 minutes of the study intervention administration on Day 1 of the Intervention Period in Group 1	Time to reach a z-score of absolute power \>2 is derived from the z-scores over time for the combined spindle and β1 frequency bands. The z-scores are calculated using an algorithm applied to the quantitative electroencephalogram (qEEG) data recorded for each study participant.
Time to reach a z-score of absolute power >2 and maintained for at least 60 seconds in the combined spindle and β1 frequency bands within the first 60 minutes of study intervention administration of iv midazolam in Group 1	Within the first 60 minutes of the study intervention administration on Day 1 of the Intervention Period in Group 1	Time to reach a z-score of absolute power \>2 is derived from the z-scores over time for the combined spindle and β1 frequency bands. The z-scores are calculated using an algorithm applied to the quantitative electroencephalogram (qEEG) data recorded for each study participant.

Secondary Outcome Measures

Name	Time	Method
Maximum concentration (Cmax) of diazepam	Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose	Cmax=maximum concentration
Area Under the Concentration Time Curve From Time 0 to Infinity (AUC) of midazolam	Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose	AUC=area under the concentration-time curve from time 0 to infinity
Occurrence of Treatment Emergent Adverse Events (TEAEs) from the first study intervention administration to the Safety Follow-Up (SFU) Visit/ Early Termination Visit (ETV)	From the first study intervention administration to the Safety Follow-Up (SFU) Visit/ Early Termination Visit (ETV) (up to 55 Days)	Treatment Emergent Adverse Events (TEAEs) are any untoward medical incidence in a participant after the administration of study treatment, whether or not these events are related to study treatment.
Occurrence of Serious TEAEs from the first study intervention administration to the Safety Follow-Up (SFU) Visit/ Early Termination Visit (ETV)	From the first study intervention administration to the Safety Follow-Up (SFU) Visit/ Early Termination Visit (ETV) (up to 55 Days)	Serious Treatment-Emergent Adverse Events (Serious TEAEs) are any untoward medical incidence in a participant during administered study treatment, whether or not these events are related to study treatment and additionally are emergent untoward medical occurrence that at any dose: Results in death; Is life-threatening; Requires in patient hospitalisation or prolongation of existing hospitalisation; Results in persistent disability/incapacity; Is a congenital anomaly or birth defect; Important medical events.
Time to reach a z-score of absolute power >2 and maintained for at least 60 seconds in the combined spindle and β1 frequency bands within the first 60 Minutes of study intervention administration of Staccato alprazolam in Group 2	Within the first 60 minutes of the study intervention administration on Day 1 of the Intervention Period in Group 2	Time to reach a z-score of absolute power \>2 is derived from the z-scores over time for the combined spindle and β1 frequency bands. The z-scores are calculated using an algorithm applied to the qEEG data recorded for each study participant.
Time to reach a z-score of absolute power >2 and maintained for at least 60 seconds in the combined spindle and β1 frequency bands within the first 60 Minutes of study intervention administration of nasal diazepam in Group 2	Within the first 60 minutes of the study intervention administration on Day 1 of the Intervention Period in Group 2	Time to reach a z-score of absolute power \>2 is derived from the z-scores over time for the combined spindle and β1 frequency bands. The z-scores are calculated using an algorithm applied to the qEEG data recorded for each study participant.
Maximum concentration (Cmax) of alprazolam	Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose	Cmax=maximum concentration
Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC[0-t]) of alprazolam	Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose	AUC(0-t)=area under the concentration-time curve from time 0 to the last quantifiable concentration
Area Under the Concentration Time Curve From Time 0 to Infinity (AUC) of alprazolam	Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose	AUC=area under the concentration-time curve from time 0 to infinity
Maximum concentration (Cmax) of midazolam	Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose	Cmax=maximum concentration
Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC[0-t]) of midazolam	Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose	AUC(0-t)=area under the concentration-time curve from time 0 to the last quantifiable concentration
Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC[0-t]) of diazepam	Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose	AUC(0-t)=area under the concentration-time curve from time 0 to the last quantifiable concentration
Area Under the Concentration Time Curve From Time 0 to Infinity (AUC) of diazepam	Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose	AUC=area under the concentration-time curve from time 0 to infinity