A Study Comparing Multiple Doses of VI-0521 With Placebo... | NCT00563368 | Trialant
NCT00563368
Sponsor
VIVUS LLC
Status
Completed
Last Update Posted
Mar 30, 2015Estimated
Enrollment
756Actual
Phase
Phase 3
Conditions
Obesity
Interventions
VI-0521
VI-0521
topiramate
topiramate
phentermine
phentermine
VI-0521
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT00563368
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
OB-301
Secondary IDs
Not provided
Brief Title
A Study Comparing Multiple Doses of VI-0521 With Placebo and Their Single-agent Constituents for Treatment of Obesity in Adults
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
Acronym
Not provided
Organization
VIVUS LLCINDUSTRY
Status Module
Record Verification Date
Mar 2015
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Dec 2007
Primary Completion Date
Sep 2008Actual
Completion Date
Sep 2008Actual
First Submitted Date
Nov 21, 2007
First Submission Date that Met QC Criteria
Nov 21, 2007
First Posted Date
Nov 26, 2007Estimated
Results Waived
Not provided
Results First Submitted Date
Jul 31, 2012
Results First Submitted that Met QC Criteria
Jul 31, 2012
Results First Posted Date
Sep 3, 2012Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Nov 18, 2009
Certification/Extension First Submitted that Passed QC Review
Nov 18, 2009
Certification/Extension First Posted Date
Nov 20, 2009Estimated
Last Update Submitted Date
Mar 10, 2015
Last Update Posted Date
Mar 30, 2015Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
VIVUS LLCINDUSTRY
Collaborators
Name
Class
Medpace, Inc.
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Detailed Description
Not provided
Conditions Module
Conditions
Obesity
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
756Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
VI-0521 Top
Experimental
VI-0521; high dose phentermine/topiramate
Drug: VI-0521
VI-0521 Mid
Experimental
VI-0521; mid dose phentermine/topiramate
Drug: VI-0521
TPM 46
Active Comparator
mid dose topiramate
Drug: topiramate
TPM 92
Active Comparator
high dose topiramate
Drug: topiramate
PHEN 7.5
Active Comparator
mid dose phentermine
Drug: phentermine
PHEN 15
Active Comparator
high dose phentermine
Drug: phentermine
Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
VI-0521
Drug
phentermine 15 mg and topiramate 92 mg, po once daily
VI-0521 Top
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percent Weight Loss From Baseline to Week 28
Percent weight loss from baseline to Week 28 with last observation carried forward (LOCF)
baseline to 28 weeks
Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF
baseline to 28 weeks
Secondary Outcomes
Not provided
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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
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.
ANCOVA
0.0009
Intersection-union method applied in a step-down testing approach
Mean Difference (Final Values)
2.76
Standard Error of the Mean
0.831
2-Sided
95
1.13
4.39
No
Superiority or Other
Primary
Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF
AEs were collected from when written informed consent was provided through 28 days after the last dose of investigational product.
Description
Only subjects who received at least one dose of study drug were included in the safety analysis.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo
Placebo
0
109
87
109
EG001
PHEN 7.5 mg
7.5 mg phentermine
2
109
85
109
EG002
TPM 46 mg
46 mg topiramate
0
106
90
106
EG003
VI-0521 Mid
7.5 mg/46 mg phentermine/topiramate
1
106
84
106
EG004
PHEN 15 mg
15 mg phentermine
1
108
88
108
EG005
TPM 92 mg
92 mg topiramate
1
107
84
107
EG006
VI-0521 Top
15 mg/92 mg phentermine/topiramate
2
108
88
108
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Humerus fracture
Injury, poisoning and procedural complications
MedDRA (10.1)
Systematic Assessment
EG0000 events0 affected109 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected106 at risk
EG0030 events0 affected106 at risk
EG004
Hypotension
Vascular disorders
MedDRA (10.1)
Systematic Assessment
EG0000 events0 affected109 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected106 at risk
EG003
Jaundice cholestatic
Hepatobiliary disorders
MedDRA (10.1)
Systematic Assessment
EG0000 events0 affected109 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected106 at risk
EG003
Malignant neoplasm of ampulia of vater
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (10.1)
Systematic Assessment
EG0000 events0 affected109 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected106 at risk
EG003
Pelvic Mass
General disorders
MedDRA (10.1)
Systematic Assessment
EG0000 events0 affected109 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected106 at risk
EG003
appendicitis
Infections and infestations
MedDRA (10.1)
Systematic Assessment
EG0000 events0 affected109 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected106 at risk
EG003
cardiac arrhythmia
Cardiac disorders
MedDRA (10.1)
Systematic Assessment
EG0000 events0 affected109 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected106 at risk
EG003
chest pain
General disorders
MedDRA (10.1)
Systematic Assessment
EG0000 events0 affected109 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected106 at risk
EG003
vision blurred
Eye disorders
MedDRA (10.1)
Systematic Assessment
EG0000 events0 affected109 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected106 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Bronchitis
Infections and infestations
MedDRA (10.1)
Systematic Assessment
EG0003 affected109 at risk
EG0012 affected109 at risk
EG0022 affected106 at risk
EG0036 affected106 at risk
EG0043 affected108 at risk
EG0052 affected107 at risk
EG0065 affected108 at risk
Upper Respiratory Tract Infection
Infections and infestations
MedDRA (10.1)
Systematic Assessment
EG00012 affected109 at risk
EG0019 affected109 at risk
EG00213 affected106 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (10.1)
Systematic Assessment
EG00011 affected109 at risk
EG0016 affected109 at risk
EG00210 affected106 at risk
EG003
Influenza
Infections and infestations
MedDRA (10.1)
Systematic Assessment
EG0005 affected109 at risk
EG0013 affected109 at risk
EG0026 affected106 at risk
EG003
Sinusitis
Infections and infestations
MedDRA (10.1)
Systematic Assessment
EG0006 affected109 at risk
EG0013 affected109 at risk
EG0025 affected106 at risk
EG003
Fatigue
General disorders
MedDRA (10.1)
Systematic Assessment
EG0007 affected109 at risk
EG0013 affected109 at risk
EG0028 affected106 at risk
EG003
Irritability
General disorders
MedDRA (10.1)
Systematic Assessment
EG0002 affected109 at risk
EG0016 affected109 at risk
EG0023 affected106 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (10.1)
Systematic Assessment
EG0006 affected109 at risk
EG0017 affected109 at risk
EG0024 affected106 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (10.1)
Systematic Assessment
EG0006 affected109 at risk
EG0019 affected109 at risk
EG0024 affected106 at risk
EG003
Vision blurred
Eye disorders
MedDRA (10.1)
Systematic Assessment
EG0005 affected109 at risk
EG0016 affected109 at risk
EG0028 affected106 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (10.1)
Systematic Assessment
EG0007 affected109 at risk
EG0012 affected109 at risk
EG0024 affected106 at risk
EG003
Headache
Nervous system disorders
MedDRA (10.1)
Systematic Assessment
EG00014 affected109 at risk
EG00114 affected109 at risk
EG0028 affected106 at risk
EG003
Paresthesia
Nervous system disorders
MedDRA (10.1)
Systematic Assessment
EG0004 affected109 at risk
EG0013 affected109 at risk
EG00212 affected106 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (10.1)
Systematic Assessment
EG0000 affected109 at risk
EG0011 affected109 at risk
EG0027 affected106 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (10.1)
Systematic Assessment
EG0002 affected109 at risk
EG0015 affected109 at risk
EG0027 affected106 at risk
EG003
Disturbance in Attention
Nervous system disorders
MedDRA (10.1)
Systematic Assessment
EG0001 affected109 at risk
EG0011 affected109 at risk
EG0022 affected106 at risk
EG003
Dry Mouth
Gastrointestinal disorders
MedDRA (10.1)
Systematic Assessment
EG0000 affected109 at risk
EG0018 affected109 at risk
EG0027 affected106 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (10.1)
Systematic Assessment
EG0009 affected109 at risk
EG0014 affected109 at risk
EG0027 affected106 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (10.1)
Systematic Assessment
EG0005 affected109 at risk
EG0015 affected109 at risk
EG0028 affected106 at risk
EG003
Diarrhea
Gastrointestinal disorders
MedDRA (10.1)
Systematic Assessment
EG0005 affected109 at risk
EG0011 affected109 at risk
EG0023 affected106 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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.
Point of Contact
Title
Organization
Phone
Extension
Email
Wesley W. Day PhD
Vivus, Inc.
650-934-5200
day@vivus.com
ID
Term
D009765
Obesity
Ancestor Terms
ID
Term
D050177
Overweight
D044343
Overnutrition
D009748
Nutrition Disorders
D009750
Nutritional and Metabolic Diseases
D001835
Body Weight
D012816
Signs and Symptoms
D013568
Pathological Conditions, Signs and Symptoms
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D000077236
Topiramate
D010645
Phentermine
Ancestor Terms
ID
Term
D005632
Fructose
D006601
Hexoses
D009005
Monosaccharides
D000073893
Sugars
D002241
Carbohydrates
D007661
Ketoses
D000662
Amphetamines
D010627
Phenethylamines
D005021
Ethylamines
D000588
Amines
D009930
Organic Chemicals
Browse Leaves
Not provided
Browse Branches
Not provided
6 subjects
FG00510 subjects
FG00617 subjects
8 subjects
FG0055 subjects
FG0064 subjects
0 subjects
FG0051 subjects
FG0063 subjects
1 subjects
FG0052 subjects
FG0060 subjects
0 subjects
FG0050 subjects
FG0060 subjects
4 subjects
FG0054 subjects
FG0060 subjects
44.6
± 11.07
BG00445.7± 12.38
BG00545.8± 11.21
BG00644.6± 12.84
BG00745.6± 11.88
86
BG00385
BG00486
BG00585
BG00685
BG007599
Male
BG00023
BG00123
BG00222
BG00322
BG00422
BG00522
BG00623
BG007157
108
BG003107
BG004108
BG005107
BG006108
BG007756
103
OG004106
OG005105
OG006103
8.5
± 0.62
OG0046.1± 0.61
OG0056.4± 0.62
OG0069.2± 0.61
OG004
OG006
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.
ANCOVA
0.0001
Intersection-union method applied in a step-down testing approach
Mean Difference (Final Values)
3.15
Standard Error of the Mean
0.825
2-Sided
95
1.53
4.77
No
Superiority or Other
OG000
OG006
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.
ANCOVA
<0.0001
Intersection-union method applied in a step-down testing approach
Mean Difference (Final Values)
7.49
Standard Error of the Mean
0.830
2-Sided
95
5.86
9.12
No
Superiority or Other
OG002
OG003
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.
ANCOVA
<0.0001
Intersection-union method applied in a step-down testing approach
Mean Difference (Final Values)
3.33
Standard Error of the Mean
0.832
2-Sided
95
1.69
4.96
No
Superiority or Other
OG001
OG003
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.
ANCOVA
0.0003
Intersection-union method applied in a step-down testing approach
Mean Difference (Final Values)
3.01
Standard Error of the Mean
0.828
2-Sided
95
1.38
4.63
No
Superiority or Other
OG000
OG003
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.
ANCOVA
<0.0001
Intersection-union method applied in a step-down testing approach
Mean Difference (Final Values)
6.75
Standard Error of the Mean
0.831
2-Sided
95
5.11
8.38
No
Superiority or Other
OG006
VI-0521 Top
15 mg/92 mg phentermine/topiramate
Units
Counts
Participants
OG000103
OG001104
OG002102
OG003103
OG004106
OG005105
OG006103
Title
Denominators
Categories
Title
Measurements
OG00015.5
OG00143.3
OG00239.2
OG00362.1
OG00446.2
OG00548.6
OG00666.0
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG005
OG006
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.
Regression, Logistic
0.0140
Intersection-union method applied in a step-down testing approach
Odds Ratio (OR)
2.028
Standard Error of the Mean
0.5832
2-Sided
95
1.154
3.563
No
Superiority or Other
OG004
OG006
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.
Regression, Logistic
0.0046
Intersection-union method applied in a step-down testing approach
Odds Ratio (OR)
2.246
Standard Error of the Mean
0.6418
2-Sided
95
1.283
3.932
No
Superiority or Other
OG000
OG006
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.
Regression, Logistic
<0.0001
Intersection-union method applied in a step-down testing approach
Odds Ratio (OR)
10.623
Standard Error of the Mean
3.6440
2-Sided
95
5.424
20.81
No
Superiority or Other
OG002
OG003
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.
Regression, Logistic
0.0011
Intersection-union method applied in a step-down testing approach
Odds Ratio (OR)
2.568
Standard Error of the Mean
0.7391
2-Sided
95
1.460
4.514
No
Superiority or Other
OG001
OG003
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.
Regression, Logistic
0.0066
Intersection-union method applied in a step-down testing approach
Odds Ratio (OR)
2.166
Standard Error of the Mean
0.6158
2-Sided
95
1.241
3.781
No
Superiority or Other
OG000
OG003
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.
Regression, Logistic
<0.0001
Intersection-union method applied in a step-down testing approach