A Study Comparing Multiple Doses of VI-0521 With Placebo and Their Single-agent Constituents for Treatment of Obesity in Adults

• Sponsor: VIVUS LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00563368
• Collaborator: Medpace, Inc. (Industry)
• Enrollment: 756
• Locations: 2
• Arms: 7
• Duration (Months): 9
• Patients Per Site: 378
• Patients Per Site Per Month: 41.8

Study Details

Study Description

Brief Summary

The objective of this study is to evaluate the safety and efficacy of various doses of VI-0521 compared to both placebo, and the single-agent components that comprise each combination dose. This study will provide confirmatory data to demonstrate that doses of VI-0521 have efficacy that is greater than placebo and each of the single-agent components that comprise the combination dose.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: VI-0521; Drug: VI-0521; Drug: topiramate; Drug: topiramate; Drug: phentermine; Drug: phentermine; Drug: VI-0521	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 756 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized, Double-Blind, Parallel-Design Study Comparing Multiple Doses of VI-0521 to Placebo and Their Single-Agent Phentermine and Topiramate Constituents for the Treatment of Obesity in Adults
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VI-0521 Top VI-0521; high dose phentermine/topiramate	Drug: VI-0521; phentermine 15 mg and topiramate 92 mg, po once daily
Experimental: VI-0521 Mid VI-0521; mid dose phentermine/topiramate	Drug: VI-0521; phentermine 7.5 mg and topiramate 46 mg, po once daily
Active Comparator: TPM 46 mid dose topiramate	Drug: topiramate; topiramate 46 mg, po once daily
Active Comparator: TPM 92 high dose topiramate	Drug: topiramate; topiramate 92 mg, po once daily
Active Comparator: PHEN 7.5 mid dose phentermine	Drug: phentermine; phentermine 7.5 mg, po once daily
Active Comparator: PHEN 15 high dose phentermine	Drug: phentermine; phentermine 15 mg, po once daily
Placebo Comparator: Placebo	Drug: VI-0521; placebo, po once daily

Outcome Measures

Primary Outcome Measures

1. Percent Weight Loss From Baseline to Week 28 [baseline to 28 weeks]

   Percent weight loss from baseline to Week 28 with last observation carried forward (LOCF)

2. Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF [baseline to 28 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 70 years of age or less with body mass index (BMI) between 30 and 45 kg/m2

• Informed Consent

• Females of child-bearing potential must be using adequate contraception

Exclusion Criteria:

• Stroke/myocardial infarction (MI)/unstable cardiovascular disease within 6 months

• Clinically significant renal, hepatic or psychiatric disease

• Unstable thyroid disease or replacement therapy

• Nephrolithiasis

• Obesity of known genetic or endocrine origin

• Participation in a formal weight loss program or lifestyle intervention

• Glaucoma or elevated intraocular pressure

• Pregnancy or breastfeeding

• Drug or Alcohol abuse

• Smoking cessation within previous 3 months or plans to quit smoking during study

• Eating disorders within past year

• Cholelithiasis within past 6 months

• Type 2 diabetes

• Previous bariatric surgery

• Bipolar disorder or psychosis

• Steroid hormone therapy not stable for 3 months

• Systolic blood pressure > 160 mmHg, diastolic blood pressure > 100 mmHg

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Durham	North Carolina	United States
2	Research Site	Philadelphia	Pennsylvania	United States

Sponsors and Collaborators

• VIVUS LLC
• Medpace, Inc.

Investigators

• Study Director: Craig Peterson, VIVUS LLC
• Study Chair: Kishore Gadde, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VIVUS LLC
• ClinicalTrials.gov Identifier: NCT00563368
• Other Study ID Numbers: OB-301
• First Posted: Nov 26, 2007
• Last Update Posted: Mar 30, 2015
• Last Verified: Mar 1, 2015

• Additional relevant MeSH terms: Obesity; Topiramate; Phentermine

Study Results

Participant Flow

Recruitment Details	Subject recruitment occurred at investigative sites in the US between November 2007 through January 2008

Arm/Group Title	Placebo	PHEN 7.5 mg	TPM 46 mg	VI-0521 Mid	PHEN 15 mg	TPM 92 mg	VI-0521 Top
Arm/Group Description	Placebo	7.5 mg phentermine	46 mg topiramate	7.5 mg/46 mg phentermine/topiramate	15 mg phentermine	92 mg topiramate	15 mg/92 mg phentermine/topiramate
Period Title: Overall Study
STARTED	109	109	108	107	108	107	108
COMPLETED	74	79	78	78	80	77	75
NOT COMPLETED	35	30	30	29	28	30	33

Baseline Characteristics

Arm/Group Title	Placebo	PHEN 7.5 mg	TPM 46 mg	VI-0521 Mid	PHEN 15 mg	TPM 92 mg	VI-0521 Top	Total
Arm/Group Description	Placebo	7.5 mg phentermine	46 mg topiramate	7.5 mg/46 mg phentermine/topiramate	15 mg phentermine	92 mg topiramate	15 mg/92 mg phentermine/topiramate	Total of all reporting groups
Overall Participants	109	109	108	107	108	107	108	756
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45 (11.43)	46.4 (11.57)	46.9 (12.62)	44.6 (11.07)	45.7 (12.38)	45.8 (11.21)	44.6 (12.84)	45.6 (11.88)
Sex: Female, Male (Count of Participants)
Female	86 78.9%	86 78.9%	86 79.6%	85 79.4%	86 79.6%	85 79.4%	85 78.7%	599 79.2%
Male	23 21.1%	23 21.1%	22 20.4%	22 20.6%	22 20.4%	22 20.6%	23 21.3%	157 20.8%
Region of Enrollment (participants) [Number]
United States	109 100%	109 100%	108 100%	107 100%	108 100%	107 100%	108 100%	756 100%

Outcome Measures

1. Primary Outcome

Title	Percent Weight Loss From Baseline to Week 28
Description	Percent weight loss from baseline to Week 28 with last observation carried forward (LOCF)
Time Frame	baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat Last-observation-carried-forward (ITT-LOCF)

Arm/Group Title	Placebo	PHEN 7.5 mg	TPM 46 mg	VI-0521 Mid	PHEN 15 mg	TPM 92 mg	VI-0521 Top
Arm/Group Description	Placebo	7.5 mg phentermine	46 mg topiramate	7.5 mg/46 mg phentermine/topiramate	15 mg phentermine	92 mg topiramate	15 mg/92 mg phentermine/topiramate
Measure Participants	103	104	102	103	106	105	103
Least Squares Mean (Standard Error) [percent weight loss]	1.7 (0.61)	5.5 (0.61)	5.1 (0.61)	8.5 (0.62)	6.1 (0.61)	6.4 (0.62)	9.2 (0.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TPM 92 mg, VI-0521 Top
	Comments	With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0009
	Comments	Intersection-union method applied in a step-down testing approach
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.76
	Confidence Interval	(2-Sided) 95%; 1.13 to 4.39
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.831
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PHEN 15 mg, VI-0521 Top
	Comments	With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	Intersection-union method applied in a step-down testing approach
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.15
	Confidence Interval	(2-Sided) 95%; 1.53 to 4.77
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.825
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, VI-0521 Top
	Comments	With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Intersection-union method applied in a step-down testing approach
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.49
	Confidence Interval	(2-Sided) 95%; 5.86 to 9.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.830
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	TPM 46 mg, VI-0521 Mid
	Comments	With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Intersection-union method applied in a step-down testing approach
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.33
	Confidence Interval	(2-Sided) 95%; 1.69 to 4.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.832
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PHEN 7.5 mg, VI-0521 Mid
	Comments	With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	Intersection-union method applied in a step-down testing approach
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.01
	Confidence Interval	(2-Sided) 95%; 1.38 to 4.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.828
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, VI-0521 Mid
	Comments	With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Intersection-union method applied in a step-down testing approach
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.75
	Confidence Interval	(2-Sided) 95%; 5.11 to 8.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.831
	Estimation Comments

2. Primary Outcome

Title	Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF
Time Frame	baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat Last-observation-carried-forward (ITT-LOCF)

Arm/Group Title	Placebo	PHEN 7.5 mg	TPM 46 mg	VI-0521 Mid	PHEN 15 mg	TPM 92 mg	VI-0521 Top
Arm/Group Description	Placebo	7.5 mg phentermine	46 mg topiramate	7.5 mg/46 mg phentermine/topiramate	15 mg phentermine	92 mg topiramate	15 mg/92 mg phentermine/topiramate
Measure Participants	103	104	102	103	106	105	103
Number [percentage of participants]	15.5 14.2%	43.3 39.7%	39.2 36.3%	62.1 58%	46.2 42.8%	48.6 45.4%	66.0 61.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TPM 92 mg, VI-0521 Top
	Comments	With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0140
	Comments	Intersection-union method applied in a step-down testing approach
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.028
	Confidence Interval	(2-Sided) 95%; 1.154 to 3.563
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5832
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PHEN 15 mg, VI-0521 Top
	Comments	With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0046
	Comments	Intersection-union method applied in a step-down testing approach
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.246
	Confidence Interval	(2-Sided) 95%; 1.283 to 3.932
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6418
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, VI-0521 Top
	Comments	With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Intersection-union method applied in a step-down testing approach
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	10.623
	Confidence Interval	(2-Sided) 95%; 5.424 to 20.81
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.6440
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	TPM 46 mg, VI-0521 Mid
	Comments	With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments	Intersection-union method applied in a step-down testing approach
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.568
	Confidence Interval	(2-Sided) 95%; 1.460 to 4.514
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7391
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PHEN 7.5 mg, VI-0521 Mid
	Comments	With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0066
	Comments	Intersection-union method applied in a step-down testing approach
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.166
	Confidence Interval	(2-Sided) 95%; 1.241 to 3.781
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6158
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, VI-0521 Mid
	Comments	With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Intersection-union method applied in a step-down testing approach
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	9.063
	Confidence Interval	(2-Sided) 95%; 4.650 to 17.66
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.0857
	Estimation Comments

Adverse Events

Time Frame	AEs were collected from when written informed consent was provided through 28 days after the last dose of investigational product.
Adverse Event Reporting Description	Only subjects who received at least one dose of study drug were included in the safety analysis.
Arm/Group Title	Placebo		PHEN 7.5 mg		TPM 46 mg		VI-0521 Mid		PHEN 15 mg		TPM 92 mg		VI-0521 Top
Arm/Group Description	Placebo		7.5 mg phentermine		46 mg topiramate		7.5 mg/46 mg phentermine/topiramate		15 mg phentermine		92 mg topiramate		15 mg/92 mg phentermine/topiramate
All Cause Mortality
	Placebo		PHEN 7.5 mg		TPM 46 mg		VI-0521 Mid		PHEN 15 mg		TPM 92 mg		VI-0521 Top
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		PHEN 7.5 mg		TPM 46 mg		VI-0521 Mid		PHEN 15 mg		TPM 92 mg		VI-0521 Top
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/109 (0%)		2/109 (1.8%)		0/106 (0%)		1/106 (0.9%)		1/108 (0.9%)		1/107 (0.9%)		2/108 (1.9%)
Cardiac disorders
cardiac arrhythmia	0/109 (0%)	0	0/109 (0%)	0	0/106 (0%)	0	0/106 (0%)	0	0/108 (0%)	0	1/107 (0.9%)	1	0/108 (0%)	0
Eye disorders
vision blurred	0/109 (0%)	0	0/109 (0%)	0	0/106 (0%)	0	0/106 (0%)	0	0/108 (0%)	0	0/107 (0%)	0	1/108 (0.9%)	1
General disorders
Pelvic Mass	0/109 (0%)	0	1/109 (0.9%)	1	0/106 (0%)	0	0/106 (0%)	0	0/108 (0%)	0	0/107 (0%)	0	0/108 (0%)	0
chest pain	0/109 (0%)	0	0/109 (0%)	0	0/106 (0%)	0	0/106 (0%)	0	1/108 (0.9%)	1	0/107 (0%)	0	0/108 (0%)	0
Hepatobiliary disorders
Jaundice cholestatic	0/109 (0%)	0	1/109 (0.9%)	1	0/106 (0%)	0	0/106 (0%)	0	0/108 (0%)	0	0/107 (0%)	0	0/108 (0%)	0
Infections and infestations
appendicitis	0/109 (0%)	0	0/109 (0%)	0	0/106 (0%)	0	1/106 (0.9%)	1	0/108 (0%)	0	0/107 (0%)	0	0/108 (0%)	0
Injury, poisoning and procedural complications
Humerus fracture	0/109 (0%)	0	0/109 (0%)	0	0/106 (0%)	0	0/106 (0%)	0	0/108 (0%)	0	0/107 (0%)	0	1/108 (0.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm of ampulia of vater	0/109 (0%)	0	1/109 (0.9%)	1	0/106 (0%)	0	0/106 (0%)	0	0/108 (0%)	0	0/107 (0%)	0	0/108 (0%)	0
Vascular disorders
Hypotension	0/109 (0%)	0	1/109 (0.9%)	1	0/106 (0%)	0	0/106 (0%)	0	0/108 (0%)	0	0/107 (0%)	0	0/108 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		PHEN 7.5 mg		TPM 46 mg		VI-0521 Mid		PHEN 15 mg		TPM 92 mg		VI-0521 Top
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	87/109 (79.8%)		85/109 (78%)		90/106 (84.9%)		84/106 (79.2%)		88/108 (81.5%)		84/107 (78.5%)		88/108 (81.5%)
Eye disorders
Vision blurred	5/109 (4.6%)		6/109 (5.5%)		8/106 (7.5%)		7/106 (6.6%)		7/108 (6.5%)		7/107 (6.5%)		5/108 (4.6%)
Gastrointestinal disorders
Dry Mouth	0/109 (0%)		8/109 (7.3%)		7/106 (6.6%)		14/106 (13.2%)		13/108 (12%)		7/107 (6.5%)		20/108 (18.5%)
Constipation	9/109 (8.3%)		4/109 (3.7%)		7/106 (6.6%)		7/106 (6.6%)		9/108 (8.3%)		6/107 (5.6%)		17/108 (15.7%)
Nausea	5/109 (4.6%)		5/109 (4.6%)		8/106 (7.5%)		9/106 (8.5%)		6/108 (5.6%)		5/107 (4.7%)		8/108 (7.4%)
Diarrhea	5/109 (4.6%)		1/109 (0.9%)		3/106 (2.8%)		4/106 (3.8%)		4/108 (3.7%)		6/107 (5.6%)		6/108 (5.6%)
General disorders
Fatigue	7/109 (6.4%)		3/109 (2.8%)		8/106 (7.5%)		6/106 (5.7%)		6/108 (5.6%)		7/107 (6.5%)		10/108 (9.3%)
Irritability	2/109 (1.8%)		6/109 (5.5%)		3/106 (2.8%)		2/106 (1.9%)		2/108 (1.9%)		1/107 (0.9%)		5/108 (4.6%)
Infections and infestations
Bronchitis	3/109 (2.8%)		2/109 (1.8%)		2/106 (1.9%)		6/106 (5.7%)		3/108 (2.8%)		2/107 (1.9%)		5/108 (4.6%)
Upper Respiratory Tract Infection	12/109 (11%)		9/109 (8.3%)		13/106 (12.3%)		14/106 (13.2%)		9/108 (8.3%)		14/107 (13.1%)		14/108 (13%)
Nasopharyngitis	11/109 (10.1%)		6/109 (5.5%)		10/106 (9.4%)		3/106 (2.8%)		10/108 (9.3%)		9/107 (8.4%)		11/108 (10.2%)
Influenza	5/109 (4.6%)		3/109 (2.8%)		6/106 (5.7%)		6/106 (5.7%)		5/108 (4.6%)		2/107 (1.9%)		6/108 (5.6%)
Sinusitis	6/109 (5.5%)		3/109 (2.8%)		5/106 (4.7%)		2/106 (1.9%)		8/108 (7.4%)		5/107 (4.7%)		4/108 (3.7%)
Musculoskeletal and connective tissue disorders
Back pain	6/109 (5.5%)		9/109 (8.3%)		4/106 (3.8%)		3/106 (2.8%)		0/108 (0%)		3/107 (2.8%)		8/108 (7.4%)
Nervous system disorders
Headache	14/109 (12.8%)		14/109 (12.8%)		8/106 (7.5%)		16/106 (15.1%)		11/108 (10.2%)		11/107 (10.3%)		17/108 (15.7%)
Paresthesia	4/109 (3.7%)		3/109 (2.8%)		12/106 (11.3%)		18/106 (17%)		5/108 (4.6%)		24/107 (22.4%)		25/108 (23.1%)
Dysgeusia	0/109 (0%)		1/109 (0.9%)		7/106 (6.6%)		9/106 (8.5%)		1/108 (0.9%)		2/107 (1.9%)		16/108 (14.8%)
Dizziness	2/109 (1.8%)		5/109 (4.6%)		7/106 (6.6%)		4/106 (3.8%)		3/108 (2.8%)		4/107 (3.7%)		9/108 (8.3%)
Disturbance in Attention	1/109 (0.9%)		1/109 (0.9%)		2/106 (1.9%)		7/106 (6.6%)		1/108 (0.9%)		4/107 (3.7%)		4/108 (3.7%)
Psychiatric disorders
Insomnia	6/109 (5.5%)		7/109 (6.4%)		4/106 (3.8%)		13/106 (12.3%)		12/108 (11.1%)		5/107 (4.7%)		11/108 (10.2%)
Respiratory, thoracic and mediastinal disorders
Cough	7/109 (6.4%)		2/109 (1.8%)		4/106 (3.8%)		1/106 (0.9%)		6/108 (5.6%)		1/107 (0.9%)		9/108 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

After Sponsor's written notification that publication of results is no longer planned or 12 months after termination of the study at all sites, Institution & PI may publish, upon written approval from Sponsor, results of the Study. Sponsor will be given the opportunity to review any proposed publication at least 60 days prior to submission for publication or disclosure. Upon Sponsor's written request, Institution and PI shall not publish or disclose information related to the Study.