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Study of VI-0521 Compared to Placebo in Treatment of Diabetes and Obesity in Adults With Obesity-Related Co-Morbid Conditions

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ClinicalTrials.gov Identifier: NCT00553787
Recruitment Status : Completed
First Posted : November 6, 2007
Results First Posted : September 6, 2012
Last Update Posted : September 10, 2012
Sponsor:
Collaborator:
Medpace, Inc.
Information provided by (Responsible Party):
VIVUS, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Obesity
Type 2 Diabetes
Intervention Drug: VI-0521
Enrollment 2487
Recruitment Details Subject recruitment occurred at investigative sites in the US between November 2007 through May 2008
Pre-assignment Details  
Arm/Group Title Placebo VI-0521 Mid VI-0521 Top
Hide Arm/Group Description [Not Specified] 7.5 mg/46 mg phentermine/topiramate 15 mg/92 mg phentermine/topiramate
Period Title: Overall Study
Started 994 498 995
Completed 616 374 733
Not Completed 378 124 262
Reason Not Completed
Adverse Event             34             21             67
Lost to Follow-up             132             44             78
Withdrawal by Subject             151             40             83
Lack of Efficacy             31             1             3
Pregnancy             0             1             2
non compliance             4             0             11
Requirement for restricted medication             8             7             5
Other             18             10             13
Arm/Group Title Placebo VI-0521 Mid VI-0521 Top Total
Hide Arm/Group Description [Not Specified] 7.5 mg/46 mg phentermine/topiramate 15 mg/92 mg phentermine/topiramate Total of all reporting groups
Overall Number of Baseline Participants 994 498 995 2487
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 994 participants 498 participants 995 participants 2487 participants
51.2  (10.3) 51.1  (10.4) 51  (10.7) 51.1  (10.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 994 participants 498 participants 995 participants 2487 participants
Female
695
  69.9%
349
  70.1%
693
  69.6%
1737
  69.8%
Male
299
  30.1%
149
  29.9%
302
  30.4%
750
  30.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 994 participants 498 participants 995 participants 2487 participants
994 498 995 2487
1.Primary Outcome
Title Percent Weight Loss From Baseline to Week 56
Hide Description [Not Specified]
Time Frame Baseline to 56 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
intent-to-treat last-observation-carried-forward (ITT-LOCF)
Arm/Group Title Placebo VI-0521 Mid VI-0521 Top
Hide Arm/Group Description:
[Not Specified]
7.5 mg/46 mg phentermine/topiramate
15 mg/92 mg phentermine/topiramate
Overall Number of Participants Analyzed 979 488 981
Least Squares Mean (Standard Error)
Unit of Measure: percent weight loss
1.24  (0.277) 7.81  (0.365) 9.84  (0.275)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, VI-0521 Top
Comments With at least 500 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Intersection-union method applied in a step-down testing approach
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 8.6
Confidence Interval (2-Sided) 95%
7.96 to 9.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.328
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, VI-0521 Mid
Comments With at least 500 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Intersection-union method applied in a step-down testing approach
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.58
Confidence Interval (2-Sided) 95%
5.79 to 7.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.403
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection VI-0521 Mid, VI-0521 Top
Comments With at least 500 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Intersection-union method applied in a step-down testing approach
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.03
Confidence Interval (2-Sided) 95%
1.24 to 2.82
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.402
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Subjects With a Weight Loss of at Least 5% at Week 56 With LOCF
Hide Description [Not Specified]
Time Frame Baseline to 56 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
intent-to-treat last-observation-carried-forward (ITT-LOCF)
Arm/Group Title Placebo VI-0521 Mid VI-0521 Top
Hide Arm/Group Description:
[Not Specified]
7.5 mg/46 mg phentermine/topiramate
15 mg/92 mg phentermine/topiramate
Overall Number of Participants Analyzed 979 488 981
Measure Type: Number
Unit of Measure: percentage of participants
20.8 62.1 70
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, VI-0521 Top
Comments With at least 500 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Intersection-union method applied in a step-down testing approach
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 9.03
Confidence Interval (2-Sided) 95%
7.34 to 11.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.955
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, VI-0521 Mid
Comments With at least 500 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Intersection-union method applied in a step-down testing approach
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.27
Confidence Interval (2-Sided) 95%
4.93 to 7.97
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.768
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection VI-0521 Mid, VI-0521 Top
Comments With at least 500 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments Intersection-union method applied in a step-down testing approach
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.44
Confidence Interval (2-Sided) 95%
1.15 to 1.81
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.169
Estimation Comments [Not Specified]
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 Mid VI-0521 Top
Hide Arm/Group Description [Not Specified] 7.5 mg/46 mg phentermine/topiramate 15 mg/92 mg phentermine/topiramate
All-Cause Mortality
Placebo VI-0521 Mid VI-0521 Top
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo VI-0521 Mid VI-0521 Top
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   40/993 (4.03%)   15/498 (3.01%)   50/994 (5.03%) 
Cardiac disorders       
coronary artery disease  1  4/993 (0.40%)  0/498 (0.00%)  1/994 (0.10%) 
myocardial ischemia  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
cardio-respiratory arrest  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
atrial fibrillation  1  1/993 (0.10%)  1/498 (0.20%)  0/994 (0.00%) 
myocardial infarction  1  0/993 (0.00%)  1/498 (0.20%)  2/994 (0.20%) 
tachycardia  1  0/993 (0.00%)  1/498 (0.20%)  0/994 (0.00%) 
acute coronary syndrome  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
angina pectoris  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Ear and labyrinth disorders       
tinnitus  1  0/993 (0.00%)  1/498 (0.20%)  0/994 (0.00%) 
vertigo  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Endocrine disorders       
goiter  1  0/993 (0.00%)  1/498 (0.20%)  0/994 (0.00%) 
Gastrointestinal disorders       
colitis  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
colitis ischemic  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
small intestinal obstruction  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
intestinal obstruction  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
gastric ulcer  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
umbilical hernia, obstructive  1  0/993 (0.00%)  1/498 (0.20%)  0/994 (0.00%) 
gastroesophageal reflux disease  1  0/993 (0.00%)  0/498 (0.00%)  2/994 (0.20%) 
esophageal spasm  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
gastric ulcer hemorrhage  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
General disorders       
catheter related complications  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
non-cardiac chest pain  1  2/993 (0.20%)  0/498 (0.00%)  1/994 (0.10%) 
chest pain  1  2/993 (0.20%)  0/498 (0.00%)  2/994 (0.20%) 
fatigue  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Hepatobiliary disorders       
cholelithiasis  1  1/993 (0.10%)  0/498 (0.00%)  1/994 (0.10%) 
cholecystitis acute  1  0/993 (0.00%)  0/498 (0.00%)  2/994 (0.20%) 
bile duct stone  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
cholecystitis  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Immune system disorders       
drug hypersensitivity  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Infections and infestations       
diverticulitis  1  1/993 (0.10%)  2/498 (0.40%)  0/994 (0.00%) 
gastroenteritis  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
bursitis infective  1  0/993 (0.00%)  1/498 (0.20%)  0/994 (0.00%) 
appendicitis  1  0/993 (0.00%)  0/498 (0.00%)  3/994 (0.30%) 
cellulitis  1  0/993 (0.00%)  0/498 (0.00%)  3/994 (0.30%) 
clostridial infection  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
lobar pneumonia  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
pneumonia  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Injury, poisoning and procedural complications       
anemia post-operative  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
tibia fracture  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
hip fracture  1  0/993 (0.00%)  1/498 (0.20%)  0/994 (0.00%) 
incisional hernia  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Investigations       
liver function test abnormal  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Metabolism and nutrition disorders       
hypokalemia  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
hyponatremia  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
dehydration  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Musculoskeletal and connective tissue disorders       
invtervertebral disc protrusion  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
arthraligia  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
gouty arthritis  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
cervical spinal stenosis  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
intervertebral disc degeneration  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
musculoskeletal chest pain  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
lumbar spinal stenosis  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
prostate cancer  1  2/993 (0.20%)  0/498 (0.00%)  0/994 (0.00%) 
lung neoplasm malignant  1  1/993 (0.10%)  0/498 (0.00%)  1/994 (0.10%) 
breast cancer metastatic  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
rectal cancer  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
breast cancer  1  1/993 (0.10%)  0/498 (0.00%)  2/994 (0.20%) 
uterine leiomyoma  1  0/993 (0.00%)  1/498 (0.20%)  0/994 (0.00%) 
endometrial cancer  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Nervous system disorders       
transient ischemic attack  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
brain stem infarction  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
syncope  1  2/993 (0.20%)  0/498 (0.00%)  1/994 (0.10%) 
headache  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
dizziness  1  0/993 (0.00%)  1/498 (0.20%)  0/994 (0.00%) 
brain mass  1  0/993 (0.00%)  1/498 (0.20%)  0/994 (0.00%) 
cerebral infarction  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Psychiatric disorders       
bipolar disorder  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Renal and urinary disorders       
renal failure acute  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
nephrolithiasis  1  0/993 (0.00%)  0/498 (0.00%)  2/994 (0.20%) 
calculus urinary  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Reproductive system and breast disorders       
pelvic pain  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
prostatitis  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
ovarian cyst ruptured  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
uterovaginal prolapse  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
coital bleeding  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Respiratory, thoracic and mediastinal disorders       
pulmonary embolism  1  1/993 (0.10%)  0/498 (0.00%)  1/994 (0.10%) 
asthma  1  1/993 (0.10%)  2/498 (0.40%)  0/994 (0.00%) 
Skin and subcutaneous tissue disorders       
urticaria  1  1/993 (0.10%)  0/498 (0.00%)  0/994 (0.00%) 
skin ulcer  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Vascular disorders       
hypertension  1  1/993 (0.10%)  0/498 (0.00%)  1/994 (0.10%) 
hypotension  1  0/993 (0.00%)  1/498 (0.20%)  1/994 (0.10%) 
deep vein thrombosis  1  0/993 (0.00%)  0/498 (0.00%)  1/994 (0.10%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo VI-0521 Mid VI-0521 Top
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   761/993 (76.64%)   424/498 (85.14%)   874/994 (87.93%) 
Gastrointestinal disorders       
constipation  1  59/993 (5.94%)  75/498 (15.06%)  173/994 (17.40%) 
dry mouth  1  24/993 (2.42%)  67/498 (13.45%)  207/994 (20.82%) 
nausea  1  42/993 (4.23%)  18/498 (3.61%)  68/994 (6.84%) 
diarrhea  1  48/993 (4.83%)  32/498 (6.43%)  58/994 (5.84%) 
General disorders       
fatigue  1  50/993 (5.04%)  22/498 (4.42%)  67/994 (6.74%) 
Infections and infestations       
Upper Respiratory Tract Infection  1  128/993 (12.89%)  61/498 (12.25%)  133/994 (13.38%) 
Nasopharyngitis  1  86/993 (8.66%)  53/498 (10.64%)  98/994 (9.86%) 
sinusitis  1  67/993 (6.75%)  34/498 (6.83%)  85/994 (8.55%) 
bronchitis  1  43/993 (4.33%)  22/498 (4.42%)  52/994 (5.23%) 
urinary tract infection  1  37/993 (3.73%)  26/498 (5.22%)  54/994 (5.43%) 
Musculoskeletal and connective tissue disorders       
back pain  1  49/993 (4.93%)  28/498 (5.62%)  72/994 (7.24%) 
arthralgia  1  54/993 (5.44%)  23/498 (4.62%)  44/994 (4.43%) 
Nervous system disorders       
headache  1  90/993 (9.06%)  35/498 (7.03%)  101/994 (10.16%) 
paresthesia  1  20/993 (2.01%)  68/498 (13.65%)  204/994 (20.52%) 
dizziness  1  31/993 (3.12%)  36/498 (7.23%)  99/994 (9.96%) 
dysgeusia  1  11/993 (1.11%)  37/498 (7.43%)  103/994 (10.36%) 
Psychiatric disorders       
insomnia  1  47/993 (4.73%)  29/498 (5.82%)  102/994 (10.26%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Wesley W Day PhD
Organization: Vivus, Inc
Phone: 650-934-5200
EMail: day@vivus.com
Layout table for additonal information
Responsible Party: VIVUS, Inc.
ClinicalTrials.gov Identifier: NCT00553787    
Other Study ID Numbers: OB-303
First Submitted: November 3, 2007
First Posted: November 6, 2007
Results First Submitted: July 31, 2012
Results First Posted: September 6, 2012
Last Update Posted: September 10, 2012