Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Alzheimer's Disease

• Sponsor: FORUM Pharmaceuticals Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00766363
• Collaborator: Syneos Health (Other)
• Enrollment: 49
• Locations: 4
• Arms: 4
• Duration (Months): 5
• Patients Per Site: 12.3
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

This study is being conducted to determine the safety, tolerability, and pharmacokinetics (PK) of three different doses of an investigational medication, EVP-6124, in individuals with mild to moderate Alzheimer's disease who are also taking an Alzheimer's medication (AChEI [acetylcholinesterase inhibitor]: either donepezil or rivastigmine). In addition, PK of AChEI medications will be assessed. Cognitive function will be evaluated on an exploratory basis.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease; Central Nervous System Diseases	Drug: EVP-6124 (0.1 mg/day); Drug: EVP-6124 (0.3 mg/day); Drug: EVP-6124 (1.0 mg/day); Drug: Comparator: Placebo; Drug: Donepezil; Drug: Rivastigmine	Phase 1

Detailed Description

This is a randomized, double-blind, placebo-controlled, Phase 1b safety study of three dose levels of EVP-6124 in subjects with mild or moderate Alzheimer's disease and who are taking an AChEI medication (donepezil or rivastigmine).

Study drug will be supplied as capsules and will be orally administered once daily for a total of 28 days. Eligible subjects will be admitted to an inpatient study unit on Day -2 (two days before the first dose of study drug is administered) and will remain confined to the inpatient study unit for a total of five days. Starting on Day 4, subjects will continue the study in the outpatient setting, with study visits on Days 7, 14, 21, and 28. Safety assessments, PK sampling, and cognitive testing will be performed inpatient and at each study visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Ascending-Dose Phase 1b Safety Study of Three Different Doses of an Alpha-7 Nicotinic Acetylcholine Receptor Agonist (EVP-6124) or Placebo in Patients With Mild to Moderate Probable Alzheimer's Disease
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EVP-6124 (0.1 mg/day)	Drug: EVP-6124 (0.1 mg/day); EVP-6124 was administered as one 0.1 mg capsule per day for 28 days.; Drug: Donepezil; Concomitant therapy with donepezil at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose. Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.; Drug: Rivastigmine; Concomitant therapy with rivastigmine at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose. Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.
Experimental: EVP-6124 (0.3 mg/day)	Drug: EVP-6124 (0.3 mg/day); EVP-6124 was administered as one 0.3 mg capsule every day for 28 days.; Drug: Donepezil; Concomitant therapy with donepezil at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose. Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.; Drug: Rivastigmine; Concomitant therapy with rivastigmine at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose. Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.
Experimental: EVP-6124 (1.0 mg/day)	Drug: EVP-6124 (1.0 mg/day); EVP-6124 was administered as one 1.0 mg capsule every day for 28 days.; Drug: Donepezil; Concomitant therapy with donepezil at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose. Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.; Drug: Rivastigmine; Concomitant therapy with rivastigmine at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose. Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.
Placebo Comparator: Placebo	Drug: Comparator: Placebo; Matching placebo was administered as one capsule per day for 28 days.; Drug: Donepezil; Concomitant therapy with donepezil at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose. Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.; Drug: Rivastigmine; Concomitant therapy with rivastigmine at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose. Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease [Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only]]

   All adverse experiences spontaneously reported by subject and/or observed by investigator and repeated clinical evaluation of physical examinations, vital signs, 12-lead ECG (electrocardiogram), ambulatory ECG, and laboratory tests (hematology/blood chemistry/urinalysis)

Secondary Outcome Measures

1. EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax) [24 hours]

   EVP-6124 PK data; Maximum Concentration (Cmax); i.e, highest concentration of drug in plasma

2. EVP-6124 PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax) [24 hours]

   EVP-6124 PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of drug in plasma

3. EVP-6124 PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h]) [24 hours]

   EVP-6124 PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot

4. Donepezil PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax) [24 hours]

   Donepezil PK data; Maximum Concentration (Cmax); i.e, highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124

5. Donepezil PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax) [24 hours]

   Donepezil PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124

6. Donepezil PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h]) [24 hours]

   Donepezil PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot for donepezil (parent compound only) after dosing with EVP-6124

7. Rivastigmine PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax) [24 hours]

   Rivastigmine PK data; Maximum Concentration (Cmax); i.e, highest concentration of rivastigmine in plasma after dosing with EVP-6124

8. Rivastigmine PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax) [24 hours]

   Rivastigmine PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of rivastigmine in plasma after dosing with EVP-6124

9. Rivastigmine PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h]) [24 hours]

   Rivastigmine PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot for rivastigmine after dosing with EVP-6124

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• male and post-menopausal or surgically sterile female pts

• 50-90 yrs old, who meet clinical criteria for probable Alzheimer's disease (Mini-Mental State Examination of 18-26; Hachinski Ischemic Score ≤4)

• must be taking donepezil or rivastigmine for at least 3 mos.

Exclusion Criteria:

• Unstable medical condition that is clinically significant in the judgment of the investigator; major organ system dysfunction

• Untreated hypothyroidism

• Insufficiently controlled diabetes mellitus

• Diagnosis of major depression requiring antidepressant medications within the last 5 years

• Stroke within 6 months before screening, or concomitant with onset of dementia

• Certain concomitant medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pacific Research Network, Inc.	San Diego	California	United States	92103
2	MD Clinical	Hallandale Beach	Florida	United States	33009
3	Comprehensive Clinical Research	Berlin	New Jersey	United States	08009
4	Global Medical Institutes, LLC	Princeton	New Jersey	United States	08540

Sponsors and Collaborators

• FORUM Pharmaceuticals Inc
• Syneos Health

Investigators

• Principal Investigator: David R. Hassmann, D.O., Comprehensive Clinical Research
• Principal Investigator: Beth Safirstein, M.D., MD Clinical
• Principal Investigator: Stephen Thein, Ph.D., Pacific Research Network, Inc.
• Principal Investigator: Jeffrey Apter, M.D., Global Medical Institutes

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: FORUM Pharmaceuticals Inc
• ClinicalTrials.gov Identifier: NCT00766363
• Other Study ID Numbers: EVP-6124-007
• First Posted: Oct 3, 2008
• Last Update Posted: Apr 20, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by FORUM Pharmaceuticals Inc: Alzheimer's Disease; Central Nervous System Diseases; Pharmacokinetics; Cognition
• Additional relevant MeSH terms: Alzheimer Disease; Nervous System Diseases; Central Nervous System Diseases; Rivastigmine; Donepezil

Study Results

Participant Flow

Recruitment Details	The recruitment period was from September 2008 to February 2009 at 4 study centers in the US (CA, FL, and 2 in NJ).
Pre-assignment Detail	61 subjects were screened and 49 subjects were enrolled.

Arm/Group Title	EVP-6124 (0.1 mg/Day)	EVP-6124 (0.3 mg/Day)	EVP-6124 (1.0 mg/Day)	Placebo
Arm/Group Description	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.
Period Title: Overall Study
STARTED	12	13	12	12
SAFETY POPULATION	12	13	11	13
PK POPULATION	12	13	10	13
COMPLETED	11	12	12	12
NOT COMPLETED	1	1	0	0

Baseline Characteristics

Arm/Group Title	EVP-6124 (0.1 mg/Day)	EVP-6124 (0.3 mg/Day)	EVP-6124 (1.0 mg/Day)	Placebo	Total
Arm/Group Description	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.	Total of all reporting groups
Overall Participants	12	13	11	13	49
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	5 41.7%	5 38.5%	4 36.4%	4 30.8%	18 36.7%
>=65 years	7 58.3%	8 61.5%	7 63.6%	9 69.2%	31 63.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.6 (8.5)	68.3 (11.1)	70.2 (12.3)	72.0 (10.5)	69.8 (10.4)
Sex: Female, Male (Count of Participants)
Female	8 66.7%	7 53.8%	6 54.5%	8 61.5%	29 59.2%
Male	4 33.3%	6 46.2%	5 45.5%	5 38.5%	20 40.8%
Region of Enrollment (participants) [Number]
United States	12 100%	13 100%	11 100%	13 100%	49 100%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease
Description	All adverse experiences spontaneously reported by subject and/or observed by investigator and repeated clinical evaluation of physical examinations, vital signs, 12-lead ECG (electrocardiogram), ambulatory ECG, and laboratory tests (hematology/blood chemistry/urinalysis)
Time Frame	Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only]

Outcome Measure Data

Analysis Population Description

Safety Population: All randomized subjects who ingested at least 1 dose of study drug.

Arm/Group Title	EVP-6124 (0.1 mg/Day)	EVP-6124 (0.3 mg/Day)	EVP-6124 (1.0 mg/Day)	Placebo
Arm/Group Description	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.
Measure Participants	12	13	11	13
Serious Adverse Events	0 0%	0 0%	0 0%	0 0%
Non-Serious Adverse Events	2 16.7%	3 23.1%	4 36.4%	4 30.8%
No Adverse Events Reported	10 83.3%	10 76.9%	7 63.6%	9 69.2%

2. Secondary Outcome

Title	EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Description	EVP-6124 PK data; Maximum Concentration (Cmax); i.e, highest concentration of drug in plasma
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters.

Arm/Group Title	EVP-6124 (0.1 mg/Day)	EVP-6124 (0.3 mg/Day)	EVP-6124 (1.0 mg/Day)
Arm/Group Description	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.
Measure Participants	12	13	10
Mean (Standard Deviation) [ng/mL]	0.0715 (0.0121)	0.1911 (0.0740)	0.6122 (0.1235)

3. Secondary Outcome

Title	EVP-6124 PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
Description	EVP-6124 PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of drug in plasma
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters.

Arm/Group Title	EVP-6124 (0.1 mg/Day)	EVP-6124 (0.3 mg/Day)	EVP-6124 (1.0 mg/Day)
Arm/Group Description	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.
Measure Participants	12	13	10
Mean (Standard Deviation) [hours]	7.70 (3.31)	7.94 (3.61)	10.72 (6.69)

4. Secondary Outcome

Title	EVP-6124 PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
Description	EVP-6124 PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters.

Arm/Group Title	EVP-6124 (0.1 mg/Day)	EVP-6124 (0.3 mg/Day)	EVP-6124 (1.0 mg/Day)
Arm/Group Description	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.
Measure Participants	12	11	7
Mean (Standard Deviation) [h*ng/mL]	1.31 (0.23)	3.89 (0.84)	11.44 (2.24)

5. Secondary Outcome

Title	Donepezil PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Description	Donepezil PK data; Maximum Concentration (Cmax); i.e, highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters.

Arm/Group Title	EVP-6124 (0.1 mg/Day)	EVP-6124 (0.3 mg/Day)	EVP-6124 (1.0 mg/Day)	Placebo
Arm/Group Description	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.
Measure Participants	10	13	7	13
Mean (Standard Deviation) [ng/mL]	29.5 (15.8)	24.7 (19.8)	39.2 (26.7)	41.9 (19.7)

6. Secondary Outcome

Title	Donepezil PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
Description	Donepezil PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters.

Arm/Group Title	EVP-6124 (0.1 mg/Day)	EVP-6124 (0.3 mg/Day)	EVP-6124 (1.0 mg/Day)	Placebo
Arm/Group Description	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.
Measure Participants	10	12	7	13
Mean (Standard Deviation) [hours]	2.30 (2.65)	1.85 (2.15)	3.31 (3.01)	3.56 (4.02)

7. Secondary Outcome

Title	Donepezil PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
Description	Donepezil PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot for donepezil (parent compound only) after dosing with EVP-6124
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters.

Arm/Group Title	EVP-6124 (0.1 mg/Day)	EVP-6124 (0.3 mg/Day)	EVP-6124 (1.0 mg/Day)	Placebo
Arm/Group Description	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.	1 capsule per day for 28 days.
Measure Participants	10	13	7	13
Mean (Standard Deviation) [h*ng/mL]	299 (179)	240 (194)	345 (225)	427 (233)

8. Secondary Outcome

Title	Rivastigmine PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Description	Rivastigmine PK data; Maximum Concentration (Cmax); i.e, highest concentration of rivastigmine in plasma after dosing with EVP-6124
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. Only 4 subjects took rivastigmine concomitantly.

Arm/Group Title	EVP-6124 (0.1 mg/Day)	EVP-6124 (1.0 mg/Day)
Arm/Group Description	1 capsule per day for 28 days.	1 capsule per day for 28 days.
Measure Participants	2	2
Mean (Standard Deviation) [ng/mL]	23.35 (5.16)	3.51 (0.37)

9. Secondary Outcome

Title	Rivastigmine PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
Description	Rivastigmine PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of rivastigmine in plasma after dosing with EVP-6124
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. Only 4 subjects took rivastigmine concomitantly.

Arm/Group Title	EVP-6124 (0.1 mg/Day)	EVP-6124 (1.0 mg/Day)
Arm/Group Description	1 capsule per day for 28 days.	1 capsule per day for 28 days.
Measure Participants	2	2
Mean (Standard Deviation) [hours]	1.00 (0.02)	12.12 (15.72)

10. Secondary Outcome

Title	Rivastigmine PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
Description	Rivastigmine PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot for rivastigmine after dosing with EVP-6124
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. Only 4 subjects took rivastigmine concomitantly.

Arm/Group Title	EVP-6124 (0.1 mg/Day)	EVP-6124 (1.0 mg/Day)
Arm/Group Description	1 capsule per day for 28 days.	1 capsule per day for 28 days.
Measure Participants	2	2
Mean (Standard Deviation) [h*ng/mL]	143.55 (85.52)	54.60 (6.28)

Adverse Events

Time Frame	Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Arm/Group Title	EVP-6124 (0.1 mg/Day)		EVP-6124 (0.3 mg/Day)		EVP-6124 (1.0 mg/Day)		Placebo
Arm/Group Description	1 capsule per day for 28 days.		1 capsule per day for 28 days.		1 capsule per day for 28 days.		1 capsule per day for 28 days.
All Cause Mortality
	EVP-6124 (0.1 mg/Day)		EVP-6124 (0.3 mg/Day)		EVP-6124 (1.0 mg/Day)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	EVP-6124 (0.1 mg/Day)		EVP-6124 (0.3 mg/Day)		EVP-6124 (1.0 mg/Day)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/13 (0%)		0/11 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	EVP-6124 (0.1 mg/Day)		EVP-6124 (0.3 mg/Day)		EVP-6124 (1.0 mg/Day)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)		3/13 (23.1%)		4/11 (36.4%)		4/13 (30.8%)
Cardiac disorders
Atrial fibrillation	0/12 (0%)	0	0/13 (0%)	0	1/11 (9.1%)	1	0/13 (0%)	0
Eye disorders
Vision blurred	0/12 (0%)	0	0/13 (0%)	0	0/11 (0%)	0	1/13 (7.7%)	1
Gastrointestinal disorders
Constipation	0/12 (0%)	0	0/13 (0%)	0	2/11 (18.2%)	2	0/13 (0%)	0
Diarrhoea	0/12 (0%)	0	1/13 (7.7%)	1	0/11 (0%)	0	0/13 (0%)	0
Flatulence	2/12 (16.7%)	2	0/13 (0%)	0	0/11 (0%)	0	0/13 (0%)	0
Nausea	2/12 (16.7%)	2	0/13 (0%)	0	0/11 (0%)	0	0/13 (0%)	0
Vomiting	0/12 (0%)	0	0/13 (0%)	0	1/11 (9.1%)	1	0/13 (0%)	0
General disorders
Vessel puncture site pain	0/12 (0%)	0	1/13 (7.7%)	1	0/11 (0%)	0	0/13 (0%)	0
Infections and infestations
Upper respiratory tract infection	0/12 (0%)	0	0/13 (0%)	0	1/11 (9.1%)	1	0/13 (0%)	0
Nervous system disorders
Headache	2/12 (16.7%)	2	0/13 (0%)	0	0/11 (0%)	0	1/13 (7.7%)	2
Somnolence	0/12 (0%)	0	0/13 (0%)	0	0/11 (0%)	0	1/13 (7.7%)	1
Psychiatric disorders
Insomnia	0/12 (0%)	0	1/13 (7.7%)	1	0/11 (0%)	0	0/13 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	0/12 (0%)	0	0/13 (0%)	0	0/11 (0%)	0	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Rash erythematous	0/12 (0%)	0	1/13 (7.7%)	1	0/11 (0%)	0	0/13 (0%)	0
Vascular disorders
Hypotension	0/12 (0%)	0	0/13 (0%)	0	0/11 (0%)	0	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted for review. At the sponsor's request, the PI will delete confidential information other than trial data and will delay publication or disclosure for up to 90 days to allow patent filings. The PI agrees that the first publication shall be a joint publication.