ObesityPhase 2NCT00339014
Safety and Efficacy of Different Combinations of Zonisamide-CR Plus Bupropion-SR to Treat Uncomplicated Obesity
A Phase 2 study testing Zonisamide CR and Bupropion SR in people with Obesity, run by Orexigen Therapeutics, Inc at 15 sites in United States.
Trial summary
The purpose of this study is to determine which of seven combinations of Zonisamide CR and Bupropion SR gives the best weight loss and is safe and well tolerated for the treatment of obesity not associated with the complications of obesity such as diabetes. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Obesity
- What is being tested?
- Zonisamide CR and Bupropion SR
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 611 participants
- Where
- 15 sitesUnited States
- Study dates
- May 2006to Aug 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Have body mass index (BMI) of 30 to 43 kg/m2
- Free from any other clinically significant illness or disease as determined by medical history and physical examination
- Non-smoker and no use of tobacco or nicotine products for at least 6 months prior to screening
- Normotensive (systolic <140 mm Hg; diastolic <90 mm Hg). Anti-hypertensive medications are allowed with the exception of adrenergic blockers, beta-blockers and clonidine. Medical regimen must be stable for at least 6 weeks
- LDL cholesterol < 190 mg/dL and triglycerides < 400 mg/dL. Medications for treatment of dyslipidemia are allowed as long as medical regimen has been stable for at least 6 weeks
- Negative serum pregnancy test in women with an intact uterus
Show all 12Show fewer
- Score < 15 for depression and score < 15 for anxiety on Hospital Anxiety and Depression Scale (HADS)
- No clinically significant abnormality on ECG
- Not on eExcluded concomitant medications
- If female with intact uterus, be non-lactating, and agree to use effective contraception throughout the study period and for 30 days after discontinuation of study drugs.
- Able to comply with all required study procedures and schedule
- Able to use and have access to a touch tone telephone and to speak and read English
Who cannot join
- Obesity of known endocrine or genetic origin
- Serious medical condition
- Serious psychiatric illness
- Active suicidal ideation; score > 2 on the Mood Assessment questionnaire
- A response to Bipolar Disorder questions indicating the presence of Bipolar Disorder
- Type I diabetes mellitus or Type II diabetes mellitus requiring pharmacotherapy
Show all 21Show fewer
- History of alcohol or drug abuse, current or within 5 years
- History of bulimia or anorexia nervosa
- History of surgical intervention for obesity
- History of seizure disorder or predisposition to seizures (e.g., history of cerebrovascular accident, significant head trauma, brain surgery, skull fracture, subdural hematoma, or alcohol withdrawal or febrile seizures)
- History of hypersensitivity to sulfonamides ("sulfa"), bupropion, or zonisamide
- History of nephrolithiasis (renal calculi)
- History of treatment with bupropion SR (Wellbutrin, Zyban) or zonisamide (Zonegran) within 12 months
- Use of drugs, herbs, or dietary supplements known to significantly affect body weight or participation in a weight loss management program within one month prior to baseline
- Loss or gain of more than 4.0 kilos within 3 months
- Women of child bearing potential not adhering to an acceptable form of contraception
- Pregnant or breast-feeding women
- Use of investigational drug, device or procedure within 30 days
- Participation in any previous clinical trial conducted by Orexigen Therapeutics
- Planned surgical procedure that can impact the conduct of the study
- Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in this study
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
CSRA Partners in Health, Inc
Augusta, Georgia, 30909
Pennington Biomedical Research Center
Baton Rouge, Louisiana, 70808
Nutrition and Weight Mangement Center Boston Medical Center
Boston, Massachusetts, 02118
MUSC Weight Mnagement Center
Charleston, South Carolina, 29425
Center for Nutrition and Preventive Medicine
Charlotte, North Carolina, 28211
The Cooper Institute
Dallas, Texas, 75230
Baylor Endocrine Center
Dallas, Texas, 75246
Center for Human Nutrition University of Colorado Health Sciences Center
Denver, Colorado, 80220
SelfCenter, PC
Fairhope, Alabama, 36532
UCLA Center for Human Nutrition
Los Angeles, California, 90095
Comprehensive Weight Control Program
New York, New York, 10021
Center for Nutrition and Metabolic Diseases
Reno, Nevada, 89557
Scripps Clinic Del Mar
San Diego, California, 92130
Springfield Diabetes and Endocrine Center
Springfield, Illinois, 62704
George Washington University Weight Management Program
Washington D.C., District of Columbia, 20037
About this study
Official title: A Dose Parallel, Randomized, Placebo-Controlled, Multicenter Study of the Safety and Efficacy of Multiple Regimens of the Combination of Zonisamide CR Plus Bupropion SR in the Treatment of Subjects With Uncomplicated Obesity
The purpose of this study is to determine which of seven combinations of Zonisamide CR and Bupropion SR gives the best weight loss and is safe and well tolerated for the treatment of obesity not associated with the complications of obesity such as diabetes. In a previous study, the combination of zonisamide and bupropion SR was shown to be effective for weight loss compared to either zonisamide, bupropion SR alone or placebo. It is thought that by adjusting the doses of each drug, giving zonisamide in a controlled release (CR) form and increasing the doses more slowly, more weight loss and less side effects can be attained.
Read the detailed description
Over the past few years, knowledge of the pathways and neural circuits that sense body energy stores has increased dramatically. In particular, it has been shown that the melanocortin system, a group of neuronal circuits in the arcuate nucleus of the hypothalamus, is the "final common pathway" for most energy state signals, and that melanocortin signaling is necessary for normal control of food intake and energy expenditure. Stimulation of POMC neurons by serotonergic and dopaminergic agents results in release of α-, β- and γ-MSH through the action of prohormone convertase-2 with a consequent decrease in appetite.A second counter-regulatory system that inhibits POMC activation is β-endorphin, which binds to a mu-opioid receptor (MOP-R) and acts as an auto-inhibitory "brake" on the activity of the melanocortin circuits. Bupropion is an approved antidepressant that blocks reuptake of serotonin and dopamine. This stimulates secretion of both α -MSH and β-endorphin. α -MSH binds to melanocortin receptors which in turn results in appetite suppression and increased energy expenditure. β-endorphin, however, binds to a mu-opioid receptor (MOP-R) and inhibits the activity of the melanocortin circuits. Zonisamide has multiple effects that may protect against seizures, including blockade of sodium channels, and reducing voltage dependent inward (T type) calcium currents, leading to neuronal stabilization. In addition to these actions, however, it is known to increase 5-hydroxytryptophan and dopamine levels, simultaneously stimulating α -MSH release while inhibiting AGRP release. Thus, the combination of bupropion and zonisamide stimulates the melanocortin system while blocking an important feedback inhibitory pathway.
The combination of zonisamide 400 mg/day and bupropion SR 300 mg/day has been shown to be more effective for weight loss than either monotherapy or placebo in subjects with uncomplicated obesity. The hypothesis for the current trial is that greater efficacy and improved tolerability can be achieved by adjusting the doses and titration of both bupropion SR and zonisamide, and by giving zonisamide in a controlled release (CR) formulation.
- Conditions
- Obesity
- Being tested
- Zonisamide CR and Bupropion SR, Placebo
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zonisamide CR and Bupropion SRDrug
Zonisamide SR and Bupropion SR
PlaceboOther
Identical placebo
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | Zonisamide SR 120 mg/day plus Bupropion SR 280 mg/day Receives: Drug: Zonisamide CR and Bupropion SR |
| Group 2 | Active comparator | Zonisamide SR 120 mg/day plus Bupropion SR 360 mg/day Receives: Drug: Zonisamide CR and Bupropion SR |
| Group 3 | Active comparator | Zonisamide SR 240 mg/day plus Bupropion SR 280 mg/day Receives: Drug: Zonisamide CR and Bupropion SR |
| Group 4 | Active comparator | Zonisamide SR 240 mg/day plus Bupropion SR 360 mg/day Receives: Drug: Zonisamide CR and Bupropion SR |
| Group 5 | Active comparator | Zonisamide SR 360 mg/day plus Bupropion SR 280 mg/day Receives: Drug: Zonisamide CR and Bupropion SR |
| Group 6 | Active comparator | Zonisamide SR 360 mg/day plus Bupropion SR 360 mg/day Receives: Drug: Zonisamide CR and Bupropion SR |
| Group 7 | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
% change in total body weight as measured between baseline and week 24 (ITT-LOCF analysis)
Measured: Baseline to week 24
Secondary outcomes (10)
Absolute change in total body weight in kg.
Measured: Baseline to week 24
Proportion of subjects achieving > 5% weight loss.
Measured: Baseline to week 24
Proportion of subjects achieving > 10% weight loss.
Measured: Baseline to week 24
Proportion of subjects achieving > 5% weight loss at week 24 who maintain response to week 48
Measured: Baseline to week 24
Change in measures of quality of life, sleep quality and sleep quantity
Measured: Baseline to week 24
Change in fasting triglycerides level
Measured: Baseline to week 24
Change in fasting blood glucose
Measured: Baseline to week 24
Change in systolic and diastolic blood pressure
Measured: Baseline to week 24
Change in HAMD-17 Maier subscale scores
Measured: Baseline to week 24
Change in Brief Assessment of Cognition composite scores
Measured: Baseline to week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2006 (estimated)
- Study startMay 2006
- Primary completionAug 2007
- Study completionAug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 611 participants (actual)
Sponsor and investigators
- Lead sponsor
- Orexigen Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Frank Greenway, MD, Principal investigator, Pennington Biomedical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00339014
- Sponsor's protocol ID
- ZB 201
- Status last verified
- Apr 2008
- First submitted
- 18 Jun 2006
- Last updated
- 22 Apr 2008
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Parallel, Randomized, Placebo-Controlled, Multicenter Study of the Safety and Efficacy of Multiple Regimens of the Combination of Zonisamide CR Plus Bupropion SR in the Treatment of Subjects With Uncomplicated Obesity
- ClinicalTrials.gov ID
- NCT00339014
- Acronym / sponsor ID
- ZB 201
- Conditions
- Obesity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 611 participants (actual)
- Lead sponsor
- Orexigen Therapeutics, IncIndustry (pharma, biotech, devices)
- Study start
- May 2006
- Primary completion
- Aug 2007 (actual)
- Study completion
- Aug 2007 (actual)
- First posted
- 20 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine which of seven combinations of Zonisamide CR and Bupropion SR gives the best weight loss and is safe and well tolerated for the treatment of obesity not associated with the complications of obesity such as diabetes. In a previous study, the combination of zonisamide and bupropion SR was shown to be effective for weight loss compared to either zonisamide, bupropion SR alone or placebo. It is thought that by adjusting the doses of each drug, giving zonisamide in a controlled release (CR) form and increasing the doses more slowly, more weight loss and less side effects can be attained.
Detailed description
Over the past few years, knowledge of the pathways and neural circuits that sense body energy stores has increased dramatically. In particular, it has been shown that the melanocortin system, a group of neuronal circuits in the arcuate nucleus of the hypothalamus, is the "final common pathway" for most energy state signals, and that melanocortin signaling is necessary for normal control of food intake and energy expenditure. Stimulation of POMC neurons by serotonergic and dopaminergic agents results in release of α-, β- and γ-MSH through the action of prohormone convertase-2 with a consequent decrease in appetite.A second counter-regulatory system that inhibits POMC activation is β-endorphin, which binds to a mu-opioid receptor (MOP-R) and acts as an auto-inhibitory "brake" on the activity of the melanocortin circuits. Bupropion is an approved antidepressant that blocks reuptake of serotonin and dopamine. This stimulates secretion of both α -MSH and β-endorphin. α -MSH binds to melanocortin receptors which in turn results in appetite suppression and increased energy expenditure. β-endorphin, however, binds to a mu-opioid receptor (MOP-R) and inhibits the activity of the melanocortin circuits. Zonisamide has multiple effects that may protect against seizures, including blockade of sodium channels, and reducing voltage dependent inward (T type) calcium currents, leading to neuronal stabilization. In addition to these actions, however, it is known to increase 5-hydroxytryptophan and dopamine levels, simultaneously stimulating α -MSH release while inhibiting AGRP release. Thus, the combination of bupropion and zonisamide stimulates the melanocortin system while blocking an important feedback inhibitory pathway.
The combination of zonisamide 400 mg/day and bupropion SR 300 mg/day has been shown to be more effective for weight loss than either monotherapy or placebo in subjects with uncomplicated obesity. The hypothesis for the current trial is that greater efficacy and improved tolerability can be achieved by adjusting the doses and titration of both bupropion SR and zonisamide, and by giving zonisamide in a controlled release (CR) formulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Drug: Zonisamide CR and Bupropion SRZonisamide SR 120 mg/day plus Bupropion SR 280 mg/day |
| Group 2 | Active comparator | Drug: Zonisamide CR and Bupropion SRZonisamide SR 120 mg/day plus Bupropion SR 360 mg/day |
| Group 3 | Active comparator | Drug: Zonisamide CR and Bupropion SRZonisamide SR 240 mg/day plus Bupropion SR 280 mg/day |
| Group 4 | Active comparator | Drug: Zonisamide CR and Bupropion SRZonisamide SR 240 mg/day plus Bupropion SR 360 mg/day |
| Group 5 | Active comparator | Drug: Zonisamide CR and Bupropion SRZonisamide SR 360 mg/day plus Bupropion SR 280 mg/day |
| Group 6 | Active comparator | Drug: Zonisamide CR and Bupropion SRZonisamide SR 360 mg/day plus Bupropion SR 360 mg/day |
| Group 7 | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Have body mass index (BMI) of 30 to 43 kg/m2
- Free from any other clinically significant illness or disease as determined by medical history and physical examination
- Non-smoker and no use of tobacco or nicotine products for at least 6 months prior to screening
- Normotensive (systolic <140 mm Hg; diastolic <90 mm Hg). Anti-hypertensive medications are allowed with the exception of adrenergic blockers, beta-blockers and clonidine. Medical regimen must be stable for at least 6 weeks
- LDL cholesterol < 190 mg/dL and triglycerides < 400 mg/dL. Medications for treatment of dyslipidemia are allowed as long as medical regimen has been stable for at least 6 weeks
Key exclusion criteria (21 listed)
- Obesity of known endocrine or genetic origin
- Serious medical condition
- Serious psychiatric illness
- Active suicidal ideation; score > 2 on the Mood Assessment questionnaire
- A response to Bipolar Disorder questions indicating the presence of Bipolar Disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zonisamide CR and Bupropion SRZonisamide SR and Bupropion SR | Drug | Group 1, Group 2, Group 3, Group 4, Group 5, Group 6 |
| PlaceboIdentical placebo | Other | Group 7 |
Primary outcome
% change in total body weight as measured between baseline and week 24 (ITT-LOCF analysis)
Time frame: Baseline to week 24
10 secondary outcomes
Absolute change in total body weight in kg.
Time frame: Baseline to week 24
Proportion of subjects achieving > 5% weight loss.
Time frame: Baseline to week 24
Proportion of subjects achieving > 10% weight loss.
Time frame: Baseline to week 24
Proportion of subjects achieving > 5% weight loss at week 24 who maintain response to week 48
Time frame: Baseline to week 24
Change in measures of quality of life, sleep quality and sleep quantity
Time frame: Baseline to week 24
Change in fasting triglycerides level
Time frame: Baseline to week 24
Change in fasting blood glucose
Time frame: Baseline to week 24
Change in systolic and diastolic blood pressure
Time frame: Baseline to week 24
Change in HAMD-17 Maier subscale scores
Time frame: Baseline to week 24
Change in Brief Assessment of Cognition composite scores
Time frame: Baseline to week 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Greenway, MD principal investigator
Pennington Biomedical Research Center
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zonisamide CR and Bupropion SR in people with Obesity, run by Orexigen Therapeutics, Inc at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
% change in total body weight as measured between baseline and week 24 (ITT-LOCF analysis) (time frame: Baseline to week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2008; AzTrials last refreshed its copy on 8 Nov 2026.