Trial Outcomes & Findings for Staccato Alprazolam and Photoparoxysmal Response (NCT NCT02351115)

Last Updated: 2021-08-10

Results Overview

Photosensitivity describes the presentation of an epileptiform EEG response (photoparoxysmal response) from exposure to intermittent photic stimulation (IPS). SPR is the number of frequency steps (2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50 and 60 Hz). between the upper and lower limits of sensitivity to IPS for that patient at that time, in order not to evoke seizures. Thus a reduction (-change) means the intervention is working (desired effect on sensitivity)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

SPR was recorded pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration The maximum change from baseline occurred at: 10 min for alprazolam 2 mg, 1 hour for alprazolam 0.5 and 1 mg and placebo

Results posted on

2021-08-10

Participant Flow

Participant milestones

Participant milestones
Measure	BEADC Patient receiving treatment sequence BEADC	CDAEB Patient receiving treatment sequence CDAEB	DEBAC Patient receiving treatment sequence DEBAC	EDBAC Patient receiving treatment sequence EDBAC	CABED Patient receiving treatment sequence CABED
Overall Study STARTED	1	1	1	1	1
Overall Study COMPLETED	1	1	1	1	1
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Staccato Alprazolam and Photoparoxysmal Response

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BEADC BEADC n=1 Participants Patient receiving treatment sequence BEADC	CDAEB n=1 Participants Patient receiving treatment sequence CDAEB	DEBAC n=1 Participants Patient receiving treatment sequence DEBAC	EDBAC n=1 Participants Patient receiving treatment sequence EDBAC	CABED n=1 Participants Patient receiving treatment sequence CABED	Total n=5 Participants Total of all reporting groups
Age, Continuous	24 years STANDARD_DEVIATION 0 • n=93 Participants	23 years STANDARD_DEVIATION 0 • n=4 Participants	27 years STANDARD_DEVIATION 0 • n=27 Participants	39 years STANDARD_DEVIATION 0 • n=483 Participants	23 years STANDARD_DEVIATION 0 • n=36 Participants	27.2 years STANDARD_DEVIATION 6.80 • n=10 Participants
Sex: Female, Male Female	1 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants	5 Participants n=10 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Ethnicity (NIH/OMB) Ethnicity · Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants	1 Participants n=10 Participants
Ethnicity (NIH/OMB) Ethnicity · Not Hispanic or Latino	1 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	4 Participants n=10 Participants
Ethnicity (NIH/OMB) Ethnicity · Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Ethnicity (NIH/OMB) Race · Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants	1 Participants n=10 Participants
Ethnicity (NIH/OMB) Race · Not Hispanic or Latino	1 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	4 Participants n=10 Participants
Ethnicity (NIH/OMB) Race · Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Region of Enrollment United States	1 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants	1 participants n=483 Participants	1 participants n=36 Participants	5 participants n=10 Participants

PRIMARY outcome

Timeframe: SPR was recorded pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration The maximum change from baseline occurred at: 10 min for alprazolam 2 mg, 1 hour for alprazolam 0.5 and 1 mg and placebo

Population: All 5 patients received all 4 treatments (crossover design)

Outcome measures

Outcome measures
Measure	Inhaled Placebo n=5 Participants All patients receiving inhaled placebo in this 4 treatment complete crossover study	Staccato Alprazolam, 0.5 mg n=5 Participants All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato Alprazolam, 1 mg n=5 Participants All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato Alprazolam, 2 mg n=5 Participants All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Maximum Observed Change From Pretreatment Baseline in the Standardized Photosensitivity Range (SPR)	-0.2 Number of frequency steps Interval -1.87 to 1.47	-4.4 Number of frequency steps Interval -6.98 to -1.82	-5.2 Number of frequency steps Interval -7.85 to -2.55	-4.8 Number of frequency steps Interval -7.99 to -1.61

SECONDARY outcome

Timeframe: Sedation was recorded pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration The maximum change from baseline occurred at:: 30 min for alprazolam 1 mg, 1 hour for alprazolam 0.5 and 2 mg, and 4 hours for placebo

Population: All 5 patients received each of the 4 treatments after washout (crossover design)

Maximum change (in mm) from pretreatment baseline in level of sedation reported by the patient on a 100 mm line anchored by Sedated (0) and Alert (100)

Outcome measures

Outcome measures
Measure	Inhaled Placebo n=5 Participants All patients receiving inhaled placebo in this 4 treatment complete crossover study	Staccato Alprazolam, 0.5 mg n=5 Participants All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato Alprazolam, 1 mg n=5 Participants All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato Alprazolam, 2 mg n=5 Participants All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Maximum Sedation Using Visual Analog Scale (Sedated-Alert)	-5.3 units on a scale Interval -23.84 to 13.34	-58 units on a scale Interval -82.77 to -33.23	-67.4 units on a scale Interval -87.47 to -47.33	-70.6 units on a scale Interval -94.06 to -47.14

SECONDARY outcome

Timeframe: Sleepiness was recorded pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration The maximum change from baseline occurred: at: 30 min for alprazolam 1 mg, 1 hour for alprazolam 0.5 and 2 mg and placebo

Population: All 5 patients received each of the 4 treatments after washout (crossover design)

Maximum change (in mm) from pretreatment baseline in level of sedation reported by each subject on a 100 mm line anchored by Sleepy (0) and Awake (100)

Outcome measures

Outcome measures
Measure	Inhaled Placebo n=5 Participants All patients receiving inhaled placebo in this 4 treatment complete crossover study	Staccato Alprazolam, 0.5 mg n=5 Participants All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato Alprazolam, 1 mg n=5 Participants All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato Alprazolam, 2 mg n=5 Participants All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Maximum Sedation Using Visual Analog Scale (Sleepy-Awake)	-9.2 units on a scale Interval -26.33 to 7.93	-54 units on a scale Interval -72.59 to -35.31	-58.8 units on a scale Interval -76.01 to -41.59	-58.8 units on a scale Interval -69.4 to -48.2

SECONDARY outcome

Timeframe: Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration

Population: PK-PD population pairs, All 5 crossover subjects by alprazolam treatment received Number of PK-PD pairs per dose (n) = 35 (7 time points x 5 subjects)

Pearson correlation of all paired plasma concentrations of alprazolam (PK) with pharmacodynamic effect on SPR (PD) for each alprazolam dose

Outcome measures

Outcome measures
Measure	Inhaled Placebo n=5 Participants All patients receiving inhaled placebo in this 4 treatment complete crossover study	Staccato Alprazolam, 0.5 mg n=5 Participants All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato Alprazolam, 1 mg n=5 Participants All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato Alprazolam, 2 mg All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Standardized Photosensitivity Range (SPR)	-0.454 correlation coefficient Standard Deviation 0.206	-0.534 correlation coefficient Standard Deviation 0.286	-0.410 correlation coefficient Standard Deviation 0.168	—

SECONDARY outcome

Timeframe: Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration

Population: PK-PD population pairs, All 5 crossover subjects by alprazolam treatment received Number of PK-PD pairs per dose (n) = 35 (7 time points x 5 subjects)

Pearson correlation of all paired plasma concentrations of alprazolam (PK) with pharmacodynamic effect on Sedation (PD) for each alprazolam dose

Outcome measures

Outcome measures
Measure	Inhaled Placebo n=5 Participants All patients receiving inhaled placebo in this 4 treatment complete crossover study	Staccato Alprazolam, 0.5 mg n=5 Participants All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato Alprazolam, 1 mg n=5 Participants All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato Alprazolam, 2 mg All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Visual Analog Scale (Sedated-Alert)	-0.350 correlation coefficient Standard Deviation 0.122	-0.567 correlation coefficient Standard Deviation 0.322	-0.623 correlation coefficient Standard Deviation 0.388	—

SECONDARY outcome

Timeframe: Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration

Population: PK-PD population pairs, All 5 crossover subjects by alprazolam treatment received Number of PK-PD pairs per dose (n) = 35 (7 time points x 5 subjects)

Pearson correlation of all paired plasma concentrations of alprazolam (PK) with pharmacodynamic effect on Sleepiness (PD) for each alprazolam dose

Outcome measures

Outcome measures
Measure	Inhaled Placebo n=5 Participants All patients receiving inhaled placebo in this 4 treatment complete crossover study	Staccato Alprazolam, 0.5 mg n=5 Participants All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato Alprazolam, 1 mg n=5 Participants All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato Alprazolam, 2 mg All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Visual Analog Scale (Sleepy-Awake)	-0.449 correlation coefficient Standard Deviation 0.201	-0.582 correlation coefficient Standard Deviation 0.339	-0.586 correlation coefficient Standard Deviation 0.343	—

Adverse Events

Inhaled Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Staccato® Alprazolam, 0.5 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Staccato® Alprazolam, 1 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Staccato® Alprazolam, 2 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Chief Medical Officer

Engage Therapeutics, Inc

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Inhaled Placebo n=5 participants at risk All patients receiving inhaled placebo in this 4 treatment complete crossover study	Staccato® Alprazolam, 0.5 mg n=5 participants at risk All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato® Alprazolam, 1 mg n=5 participants at risk All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	Staccato® Alprazolam, 2 mg n=5 participants at risk All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Eye disorders Eye irritation	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Eye disorders Lacrimation increased	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Gastrointestinal disorders Diarrhea	40.0% 2/5 • Number of events 2 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Gastrointestinal disorders Dysgeusia	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	40.0% 2/5 • Number of events 2 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	40.0% 2/5 • Number of events 2 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	40.0% 2/5 • Number of events 2 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Gastrointestinal disorders Oral dysaesthesia	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	40.0% 2/5 • Number of events 2 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	40.0% 2/5 • Number of events 2 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Gastrointestinal disorders Retching	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Gastrointestinal disorders Vomiting	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
General disorders Pyrexia	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Infections and infestations Upper respiratory tract infection	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Injury, poisoning and procedural complications Contusion	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Injury, poisoning and procedural complications Ligament sprain	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Nervous system disorders Amnesia	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Nervous system disorders Headache	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Nervous system disorders Sedation	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	40.0% 2/5 • Number of events 2 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Nervous system disorders Somnolence	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	40.0% 2/5 • Number of events 2 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	40.0% 2/5 • Number of events 2 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Respiratory, thoracic and mediastinal disorders Cough	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	40.0% 2/5 • Number of events 2 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	40.0% 2/5 • Number of events 2 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Respiratory, thoracic and mediastinal disorders Throat tightness	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.
Skin and subcutaneous tissue disorders Rash	20.0% 1/5 • Number of events 1 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.	0.00% 0/5 • Each subject was questioned about adverse events (AEs) at 2 min, 10 min, 30 min, 1 hr, 2 hr, 4 hr, and 6 hr post study drug administration for each study drug.