Study of VI-0521 Compared to Placebo in Treatment of Obesity in Adults

• Sponsor: VIVUS LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00554216
• Collaborator: Medpace, Inc. (Industry)
• Enrollment: 1,267
• Locations: 5
• Arms: 3
• Duration (Months): 18
• Patients Per Site: 253.4
• Patients Per Site Per Month: 14.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of two doses of VI-0521 compared to placebo in treatment of obesity in an adult population with BMI ≥ 35.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 1267 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized, Double-Blind, Placebo-Controlled Multicenter Study to Determine the Safety and Efficacy of VI-0521 in the Treatment of Obesity in an Adult Population With BMI ≥ 35
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VI-0521 Low VI-0521; low dose phentermine/topiramate (PHEN/TPM 3.75 mg/23 mg)	Drug: VI-0521; 3.75 mg phentermine/23 mg topiramate
Experimental: VI-0521 Top Top Dose VI-0521 consisting of 15 mg of Phentermine and 92 mg of Topiramate.	Drug: VI-0521; 15 mg phentermine/92 mg topiramate
Placebo Comparator: Placebo Placebo to match	Drug: Placebo matched phentermine/topiramate; Placebo matched phentermine/topiramate

Outcome Measures

Primary Outcome Measures

1. Percent Weight Loss From Baseline to Week 56 [baseline to 56 weeks]

2. Percentage of Subjects With at Least 5% Weight Loss at Week 56 [baseline to 56 weeks]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Body mass index (BMI) ≥ 35 kg/m2

• Informed consent

• 70 years of age or less

• Triglyceride level ≤ 200 mg/dL with treatment of 0 or 1 medications

• Blood pressure of ≤ 140/90 mmHg with treatment of 0-2 medications for hypertension

• Fasting blood glucose level of ≤ 110 mg/dL

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

• History of glaucoma or intraocular pressure

• Pregnancy or breastfeeding

• Alcohol abuse

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

• Eating disorders

• Cholelithiasis within past 6 months

• Excluded medications

• Type 2 diabetes

• Previous bariatric surgery

• History of bipolar disorder or psychosis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	San Diego	California	United States	92130
2	Research	Ridgefield	Connecticut	United States	06877
3	Research Site	Durham	North Carolina	United States	27710
4	Research Site	Toledo	Ohio	United States	43623
5	Research Site	Austin	Texas	United States	78731

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: NCT00554216
• Other Study ID Numbers: OB-302
• First Posted: Nov 6, 2007
• Last Update Posted: Sep 10, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by VIVUS LLC: Obesity, morbid obesity
• 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 May 2008

Arm/Group Title	Placebo	VI-0521 Low	VI-0521 Top
Arm/Group Description	PHEN/TPM 3.75 mg/23 mg	PHEN/TPM 15 mg/92 mg
Period Title: Overall Study
STARTED	514	241	512
COMPLETED	272	147	340
NOT COMPLETED	242	94	172

Baseline Characteristics

Arm/Group Title	Placebo	VI-0521 Low	VI-0521 Top	Total
Arm/Group Description	PHEN/TPM 3.75/23	PHEN/TPM 15/92	Total of all reporting groups
Overall Participants	514	241	512	1267
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.0 (11.76)	43.0 (10.96)	42.0 (12.21)	42.6 (11.80)
Sex: Female, Male (Count of Participants)
Female	425 82.7%	201 83.4%	424 82.8%	1050 82.9%
Male	89 17.3%	40 16.6%	88 17.2%	217 17.1%
Region of Enrollment (participants) [Number]
United States	514 100%	241 100%	512 100%	1267 100%

Outcome Measures

1. Primary Outcome

Title	Percent Weight Loss From Baseline to Week 56
Time Frame	baseline to 56 weeks

Outcome Measure Data

Analysis Population Description

intent-to-treat last-observation-carried-forward (ITT-LOCF)

Arm/Group Title	Placebo	VI-0521 Low	VI-0521 Top
Arm/Group Description	PHEN/TPM 3.75 mg/23 mg	PHEN/TPM 15 mg/92 mg
Measure Participants	498	234	498
Least Squares Mean (Standard Error) [percent weight loss]	1.55 (0.395)	5.10 (0.538)	10.92 (0.392)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, VI-0521 Top
	Comments	With at least 250 subjects in each of the 3 arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and 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	9.36
	Confidence Interval	(2-Sided) 95%; 8.43 to 10.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.476
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, VI-0521 Low
	Comments	With at least 250 subjects in each of the 3 arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and 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	3.54
	Confidence Interval	(2-Sided) 95%; 2.38 to 4.71
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.596
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	VI-0521 Low, VI-0521 Top
	Comments	With at least 250 subjects in each of the 3 arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and 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	5.82
	Confidence Interval	(2-Sided) 95%; 4.65 to 6.99
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.596
	Estimation Comments

2. Primary Outcome

Title	Percentage of Subjects With at Least 5% Weight Loss at Week 56
Time Frame	baseline to 56 weeks

Outcome Measure Data

Analysis Population Description

intent-to-treat last-observation-carried-forward (ITT-LOCF)

Arm/Group Title	Placebo	VI-0521 Low	VI-0521 Top
Arm/Group Description	PHEN/TPM 3.75 mg/23 mg	PHEN/TPM 15 mg/92 mg
Measure Participants	498	234	498
Number [percentage of participants]	17.3 3.4%	44.9 18.6%	66.7 13%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, VI-0521 Top
	Comments	With at least 250 subjects in each of the 3 arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and 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	9.61
	Confidence Interval	(2-Sided) 95%; 7.13 to 12.95
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.463
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, VI-0521 Low
	Comments	With at least 250 subjects in each of the 3 arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and 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	3.97
	Confidence Interval	(2-Sided) 95%; 2.80 to 5.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.706
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	VI-0521 Low, VI-0521 Top
	Comments	With at least 250 subjects in each of the 3 arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and 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	2.42
	Confidence Interval	(2-Sided) 95%; 1.76 to 3.33
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.394
	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		VI-0521 Low		VI-0521 Top
Arm/Group Description	PHEN/TPM 3.75/23		PHEN/TPM 15/92
All Cause Mortality
	Placebo		VI-0521 Low		VI-0521 Top
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		VI-0521 Low		VI-0521 Top
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/513 (2.7%)		6/240 (2.5%)		13/511 (2.5%)
Cardiac disorders
angina pectoris	1/513 (0.2%)		0/240 (0%)		0/511 (0%)
myocardial infarction	0/513 (0%)		1/240 (0.4%)		0/511 (0%)
atrial fibrillation	0/513 (0%)		0/240 (0%)		1/511 (0.2%)
Ear and labyrinth disorders
Meniere's disease	1/513 (0.2%)		0/240 (0%)		0/511 (0%)
Gastrointestinal disorders
pancreatitus	1/513 (0.2%)		0/240 (0%)		0/511 (0%)
General disorders
Chest Pain	1/513 (0.2%)		0/240 (0%)		0/511 (0%)
Hepatobiliary disorders
Cholelithiasis	3/513 (0.6%)		1/240 (0.4%)		1/511 (0.2%)
Cholangitis	1/513 (0.2%)		0/240 (0%)		0/511 (0%)
Immune system disorders
hypersensitivity	0/513 (0%)		0/240 (0%)		1/511 (0.2%)
Infections and infestations
cellulitis	0/513 (0%)		1/240 (0.4%)		0/511 (0%)
appendicitis	0/513 (0%)		1/240 (0.4%)		0/511 (0%)
abdominal wall abscess	0/513 (0%)		0/240 (0%)		1/511 (0.2%)
staphylococcal infection	0/513 (0%)		0/240 (0%)		1/511 (0.2%)
Metabolism and nutrition disorders
electrolyte imbalance	0/513 (0%)		0/240 (0%)		1/511 (0.2%)
Musculoskeletal and connective tissue disorders
spinal osteoarthritis	1/513 (0.2%)		0/240 (0%)		0/511 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
prostate cancer	2/513 (0.4%)		0/240 (0%)		0/511 (0%)
metastatic neoplasm	0/513 (0%)		0/240 (0%)		1/511 (0.2%)
breast cancer	0/513 (0%)		0/240 (0%)		1/511 (0.2%)
myeloid leukemia	0/513 (0%)		0/240 (0%)		1/511 (0.2%)
Pregnancy, puerperium and perinatal conditions
abortion missed	0/513 (0%)		0/240 (0%)		1/511 (0.2%)
Psychiatric disorders
suicidal ideation	0/513 (0%)		0/240 (0%)		1/511 (0.2%)
Renal and urinary disorders
hematuria	1/513 (0.2%)		0/240 (0%)		0/511 (0%)
Reproductive system and breast disorders
Uterine Proplapse	1/513 (0.2%)		0/240 (0%)		0/511 (0%)
uterine polyp	1/513 (0.2%)		0/240 (0%)		0/511 (0%)
Respiratory, thoracic and mediastinal disorders
pulmonary embolism	1/513 (0.2%)		0/240 (0%)		1/511 (0.2%)
Vascular disorders
hypertension	1/513 (0.2%)		0/240 (0%)		0/511 (0%)
deep vein thrombosis	0/513 (0%)		1/240 (0.4%)		1/511 (0.2%)
thrombophlebitis superficial	0/513 (0%)		1/240 (0.4%)		0/511 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		VI-0521 Low		VI-0521 Top
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	374/513 (72.9%)		192/240 (80%)		432/511 (84.5%)
Eye disorders
vision blurred	16/513 (3.1%)		15/240 (6.3%)		23/511 (4.5%)
Gastrointestinal disorders
constipation	35/513 (6.8%)		19/240 (7.9%)		72/511 (14.1%)
dry mouth	19/513 (3.7%)		16/240 (6.7%)		87/511 (17%)
nausea	24/513 (4.7%)		14/240 (5.8%)		37/511 (7.2%)
diarrhea	23/513 (4.5%)		12/240 (5%)		24/511 (4.7%)
General disorders
fatigue	17/513 (3.3%)		12/240 (5%)		23/511 (4.5%)
Infections and infestations
upper respiratory tract infection	56/513 (10.9%)		38/240 (15.8%)		63/511 (12.3%)
nasopharyngitis	37/513 (7.2%)		30/240 (12.5%)		46/511 (9%)
sinusitis	28/513 (5.5%)		18/240 (7.5%)		37/511 (7.2%)
influenza	24/513 (4.7%)		18/240 (7.5%)		26/511 (5.1%)
bronchitis	22/513 (4.3%)		16/240 (6.7%)		28/511 (5.5%)
Musculoskeletal and connective tissue disorders
back pain	26/513 (5.1%)		13/240 (5.4%)		28/511 (5.5%)
Nervous system disorders
headache	52/513 (10.1%)		25/240 (10.4%)		61/511 (11.9%)
paresthesia	10/513 (1.9%)		10/240 (4.2%)		96/511 (18.8%)
dizziness	21/513 (4.1%)		7/240 (2.9%)		29/511 (5.7%)
dysgeusia	5/513 (1%)		3/240 (1.3%)		43/511 (8.4%)
Psychiatric disorders
insomnia	25/513 (4.9%)		12/240 (5%)		40/511 (7.8%)
Respiratory, thoracic and mediastinal disorders
cough	18/513 (3.5%)		8/240 (3.3%)		26/511 (5.1%)

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.