Staccato Alprazolam and Photoparoxysmal Response

• Sponsor: Alexza Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02351115
• Collaborator: The Epilepsy Study Consortium (Other)
• Enrollment: 5
• Locations: 3
• Arms: 5
• Duration (Months): 18
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether people who usually have photosensitive epilepsy will show a reduction in epileptic activity when they take a single dose of Staccato Alprazolam as compared to placebo.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: A=Placebo; Drug: B=Inhaled Alprazolam 0.5 mg; Drug: C=Inhaled Alprazolam 1 m; Drug: D= Inhaled Alprazolam 2 mg; Drug: E=Placebo	Phase 2

Detailed Description

The purpose of this study is to determine whether people who usually have photosensitive epilepsy will show a reduction in epileptic activity when they take a single dose of Staccato Alprazolam as compared to placebo. People with photosensitive epilepsy have changes on their electroencephalogram (EEG) when shown flashing lights. Three dose levels of Staccato Alprazolam will be compared to placebo.

This study will also assess the level of sedation of Staccato Alprazolam compared to placebo.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Assessment of Staccato® Alprazolam on the EEG Photoparoxysmal Response in Patients With Epilepsy
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequence BEADC A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo	Drug: A=Placebo; Drug: B=Inhaled Alprazolam 0.5 mg; Drug: C=Inhaled Alprazolam 1 m; Drug: D= Inhaled Alprazolam 2 mg; Drug: E=Placebo
Experimental: Sequence CDAEB A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo	Drug: A=Placebo; Drug: B=Inhaled Alprazolam 0.5 mg; Drug: C=Inhaled Alprazolam 1 m; Drug: D= Inhaled Alprazolam 2 mg; Drug: E=Placebo
Experimental: Sequence DEBAC A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo	Drug: A=Placebo; Drug: B=Inhaled Alprazolam 0.5 mg; Drug: C=Inhaled Alprazolam 1 m; Drug: D= Inhaled Alprazolam 2 mg; Drug: E=Placebo
Experimental: Sequence EDBAC A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo	Drug: A=Placebo; Drug: B=Inhaled Alprazolam 0.5 mg; Drug: C=Inhaled Alprazolam 1 m; Drug: D= Inhaled Alprazolam 2 mg; Drug: E=Placebo
Experimental: Sequence CABED A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo	Drug: A=Placebo; Drug: B=Inhaled Alprazolam 0.5 mg; Drug: C=Inhaled Alprazolam 1 m; Drug: D= Inhaled Alprazolam 2 mg; Drug: E=Placebo

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Change From Pretreatment Baseline in the Standardized Photosensitivity Range (SPR) [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]

   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)

Secondary Outcome Measures

1. Maximum Sedation Using Visual Analog Scale (Sedated-Alert) [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]

   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)

2. Maximum Sedation Using Visual Analog Scale (Sleepy-Awake) [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]

   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)

3. Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Standardized Photosensitivity Range (SPR) [Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration]

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

4. Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Visual Analog Scale (Sedated-Alert) [Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration]

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

5. Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Visual Analog Scale (Sleepy-Awake) [Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female subjects between the ages of 18 to 60 years, inclusive

• Body mass index (BMI) ≥18 and ≤35 kg/m2

• Able to speak, read, and understand English and willing and able to provide written informed consent on an IRB-approved form before the initiation of any study procedures

• A diagnosis and history of a photoparoxysmal response on EEG with or without a diagnosis of epilepsy for which patients are on 0-2 concomitant antiepileptic drugs

• At least 3 of the EEGs performed during the screen visit must have a reproducible IPS-induced photoparoxysmal response (PPR) on EEG of at least 3 points on a frequency assessment scale in at least one eye condition

• In otherwise good general health as determined by a complete medical history, physical examination, 12-lead ECG, blood chemistry profile, hematology, and urinalysis

• Female participants (if of child-bearing potential and sexually active) and male participants (if sexually active with a partner of child-bearing potential) who agree to use a medically acceptable and effective birth control method throughout the study and for 1 week following the end of the study. Medically acceptable methods of contraception that may be used by the participant and/or his/her partner include abstinence, birth control pills or patches, diaphragm with spermicide, intrauterine device (IUD), surgical sterilization, and progestin implant or injection. Prohibited methods include: the rhythm method, withdrawal, condoms alone, or diaphragm alone

Exclusion Criteria:

• History of non-epileptic seizures (e.g. metabolic, structural, or pseudo-seizures)

• History of seizure worsening in response to narrow spectrum drugs

• An active CNS infection, demyelinating disease, degenerative neurological disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results

• Use of more than 2 concomitant AEDs for epilepsy treatment

• Subjects taking known inhibitors or inducers of CYP3A , including carbamazepine

• Subjects with a history of allergic reactions to alprazolam or other benzodiazepines

• Treatment with an investigational drug within 30 days (or within 5 half-lives of the investigational drug, if >30 days) before Visit 2

• A history within the past 1 year of drug or alcohol dependence or abuse

• Positive urine screen for drugs of abuse at Visit 1 - Screening

• A history of HIV-positivity

• Female subjects who have a positive pregnancy test at screening or prior to test sessions or are breastfeeding

• History of acute narrow angle glaucoma, Parkinson's disease, hydrocephalus, or history of significant head trauma

• Subjects who have a current history of asthma, chronic obstructive lung disease (COPD), or any lung disease associated with bronchospasm

• Subjects who use medications to treat airways disease, such as asthma or COPD

• Subjects who have any acute respiratory signs/symptoms (e.g., wheezing)

• Clinically significant ECG abnormality including (but not limited to) any of the following conduction abnormalities or dysrhythmias: atrial fibrillation, mean QTcF (QT interval corrected for heart rate using Fridericia's method) interval >450 msec, ventricular rate <45 beats/min, second or third degree AV block, left bundle branch block, or evidence of prior myocardial infarction (MI) or acute ischemia

• Hypotension (systolic blood pressure ≤90 mm Hg, diastolic blood pressure ≤50 mm Hg), or hypertension (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥100 mm Hg) measured while seated at screening or baseline

• Significant hepatic, renal, gastroenterologic, cardiovascular (including ischemic heart disease and congestive heart failure), endocrine, neurologic (including history of seizures or stroke), or hematologic disease

• Any other disease or condition, by history, physical examination, or laboratory abnormalities that in the investigator's opinion, would present undue risk to the subject, or may confound the interpretation of study results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Consultants in Epilepsy & Neurology, PLLC	Boise	Idaho	United States
2	New York University Epilepsy Center	New York	New York	United States
3	University of Pennsylvania - Penn Epilepsy Center	Philadelphia	Pennsylvania	United States

Sponsors and Collaborators

• Alexza Pharmaceuticals, Inc.
• The Epilepsy Study Consortium

Investigators

• Study Chair: J Isojarvi, MD, Engage Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alexza Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02351115
• Other Study ID Numbers: AMDC-002-202
• First Posted: Jan 30, 2015
• Last Update Posted: Aug 10, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Epilepsy; Alprazolam

Study Results

Participant Flow

Arm/Group Title	BEADC	CDAEB	DEBAC	EDBAC	CABED
Arm/Group Description	Patient receiving treatment sequence BEADC	Patient receiving treatment sequence CDAEB	Patient receiving treatment sequence DEBAC	Patient receiving treatment sequence EDBAC	Patient receiving treatment sequence CABED
Period Title: Overall Study
STARTED	1	1	1	1	1
COMPLETED	1	1	1	1	1
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	BEADC BEADC	CDAEB	DEBAC	EDBAC	CABED	Total
Arm/Group Description	Patient receiving treatment sequence BEADC	Patient receiving treatment sequence CDAEB	Patient receiving treatment sequence DEBAC	Patient receiving treatment sequence EDBAC	Patient receiving treatment sequence CABED	Total of all reporting groups
Overall Participants	1	1	1	1	1	5
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24 (0)	23 (0)	27 (0)	39 (0)	23 (0)	27.2 (6.80)
Sex: Female, Male (Count of Participants)
Female	1 100%	1 100%	1 100%	1 100%	1 100%	5 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	1 100%	1 20%
Not Hispanic or Latino	1 100%	1 100%	1 100%	1 100%	0 0%	4 80%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	1 100%	1 20%
Not Hispanic or Latino	1 100%	1 100%	1 100%	1 100%	0 0%	4 80%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	1 100%	1 100%	1 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Change From Pretreatment Baseline in the Standardized Photosensitivity Range (SPR)
Description	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)
Time Frame	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

Outcome Measure Data

Analysis Population Description

All 5 patients received all 4 treatments (crossover design)

Arm/Group Title	Inhaled Placebo	Staccato Alprazolam, 0.5 mg	Staccato Alprazolam, 1 mg	Staccato Alprazolam, 2 mg
Arm/Group Description	All patients receiving inhaled placebo in this 4 treatment complete crossover study	All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Measure Participants	5	5	5	5
Mean (90% Confidence Interval) [Number of frequency steps]	-0.2	-4.4	-5.2	-4.8

2. Secondary Outcome

Title	Maximum Sedation Using Visual Analog Scale (Sedated-Alert)
Description	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)
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Inhaled Placebo	Staccato Alprazolam, 0.5 mg	Staccato Alprazolam, 1 mg	Staccato Alprazolam, 2 mg
Arm/Group Description	All patients receiving inhaled placebo in this 4 treatment complete crossover study	All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Measure Participants	5	5	5	5
Mean (90% Confidence Interval) [units on a scale]	-5.3	-58	-67.4	-70.6

3. Secondary Outcome

Title	Maximum Sedation Using Visual Analog Scale (Sleepy-Awake)
Description	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)
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Inhaled Placebo	Staccato Alprazolam, 0.5 mg	Staccato Alprazolam, 1 mg	Staccato Alprazolam, 2 mg
Arm/Group Description	All patients receiving inhaled placebo in this 4 treatment complete crossover study	All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Measure Participants	5	5	5	5
Mean (90% Confidence Interval) [units on a scale]	-9.2	-54	-58.8	-58.8

4. Secondary Outcome

Title	Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Standardized Photosensitivity Range (SPR)
Description	Pearson correlation of all paired plasma concentrations of alprazolam (PK) with pharmacodynamic effect on SPR (PD) for each alprazolam dose
Time Frame	Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Staccato Alprazolam, 0.5 mg	Staccato Alprazolam, 1 mg	Staccato Alprazolam, 2 mg
Arm/Group Description	All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Measure Participants	5	5	5
Mean (Standard Deviation) [correlation coefficient]	-0.454 (0.206)	-0.534 (0.286)	-0.410 (0.168)

5. Secondary Outcome

Title	Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Visual Analog Scale (Sedated-Alert)
Description	Pearson correlation of all paired plasma concentrations of alprazolam (PK) with pharmacodynamic effect on Sedation (PD) for each alprazolam dose
Time Frame	Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Staccato Alprazolam, 0.5 mg	Staccato Alprazolam, 1 mg	Staccato Alprazolam, 2 mg
Arm/Group Description	All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Measure Participants	5	5	5
Mean (Standard Deviation) [correlation coefficient]	-0.350 (0.122)	-0.567 (0.322)	-0.623 (0.388)

6. Secondary Outcome

Title	Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Visual Analog Scale (Sleepy-Awake)
Description	Pearson correlation of all paired plasma concentrations of alprazolam (PK) with pharmacodynamic effect on Sleepiness (PD) for each alprazolam dose
Time Frame	Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Staccato Alprazolam, 0.5 mg	Staccato Alprazolam, 1 mg	Staccato Alprazolam, 2 mg
Arm/Group Description	All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study	All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study	All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
Measure Participants	5	5	5
Mean (Standard Deviation) [correlation coefficient]	-0.449 (0.201)	-0.582 (0.339)	-0.586 (0.343)

Adverse Events

Time Frame	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.
Arm/Group Title	Inhaled Placebo		Staccato® Alprazolam, 0.5 mg		Staccato® Alprazolam, 1 mg		Staccato® Alprazolam, 2 mg
Arm/Group Description	All patients receiving inhaled placebo in this 4 treatment complete crossover study		All patients receiving 0.5 mg inhaled alprazolam in this 4 treatment complete crossover study		All patients receiving 1 mg inhaled alprazolam in this 4 treatment complete crossover study		All patients receiving 2 mg inhaled alprazolam in this 4 treatment complete crossover study
All Cause Mortality
	Inhaled Placebo		Staccato® Alprazolam, 0.5 mg		Staccato® Alprazolam, 1 mg		Staccato® Alprazolam, 2 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Inhaled Placebo		Staccato® Alprazolam, 0.5 mg		Staccato® Alprazolam, 1 mg		Staccato® Alprazolam, 2 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Inhaled Placebo		Staccato® Alprazolam, 0.5 mg		Staccato® Alprazolam, 1 mg		Staccato® Alprazolam, 2 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		2/5 (40%)		3/5 (60%)		4/5 (80%)
Eye disorders
Eye irritation	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Lacrimation increased	0/5 (0%)	0	1/5 (20%)	1	1/5 (20%)	1	1/5 (20%)	1
Gastrointestinal disorders
Abdominal pain upper	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0
Diarrhea	2/5 (40%)	2	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Dysgeusia	1/5 (20%)	1	2/5 (40%)	2	2/5 (40%)	2	2/5 (40%)	2
Oral dysaesthesia	0/5 (0%)	0	2/5 (40%)	2	0/5 (0%)	0	2/5 (40%)	2
Retching	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Vomiting	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
General disorders
Pyrexia	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Infections and infestations
Upper respiratory tract infection	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Ligament sprain	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Nervous system disorders
Amnesia	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Headache	1/5 (20%)	1	1/5 (20%)	1	1/5 (20%)	1	0/5 (0%)	0
Sedation	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	2/5 (40%)	2
Somnolence	1/5 (20%)	1	1/5 (20%)	1	2/5 (40%)	2	2/5 (40%)	2
Respiratory, thoracic and mediastinal disorders
Cough	1/5 (20%)	1	2/5 (40%)	2	1/5 (20%)	1	2/5 (40%)	2
Oropharyngeal pain	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Pulmonary congestion	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Throat irritation	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	1/5 (20%)	1
Throat tightness	0/5 (0%)	0	1/5 (20%)	1	1/5 (20%)	1	0/5 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.