Official Title: “A Randomized, Double-Blind, Placebo-Controlled Trial to Assess Safety and Tolerability During Treatment of Type 2 Diabetes With Usual Diabetes Therapy and Either Cycloset or Placebo”

Cycloset, a new quick-release oral formulation of bromocriptine mesylate, effectively reduces blood sugar by the proposed mechanism of reversing many of the metabolic alterations associated with insulin resistance and obesity by resetting central (hypothalamic) circadian organization of monoamine neuronal activities.

The primary analysis of this study will test the hypothesis that the rate of all-cause severe adverse events for those receiving usual drug therapy for diabetes management plus Cycloset is not greater than that for usual drug therapy plus placebo by more than an acceptable margin. While the primary purpose of this study is to establish the safety profile of Cycloset in type 2 diabetes, any potential positive cardiovascular benefits will be evaluated as well.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Safety Study

Bromocriptine mesylate, an ergot derivative, is a sympatholytic dopamine D2 receptor agonist that can exert inhibitory effects on serotonin turnover in the central nervous system. It has been proposed that bromocriptine can reverse many of the metabolic alterations associated with insulin resistance and obesity by resetting central (hypothalamic) circadian organization of monoamine neuronal activities.

While Cycloset has demonstrated efficacy by reducing HbA1c, fasting and post-prandial glucose and fasting and post-prandial triglycerides, the relatively small numbers of individuals treated for type 2 diabetes during the controlled Phase III clinical trials of Cycloset did not allow for a full evaluation of the safety profile. Since persons with diabetes are already at higher risk for cardiovascular disease, it is important to examine more fully the spectrum of potential adverse or positive effects from Cycloset in a large sample of persons with diabetes. Accordingly, the present study is designed to investigate the clinical safety of treatment with Cycloset in a broad population of persons with type 2 diabetes.

To determine in subjects with type 2 diabetes mellitus receiving Usual Diabetes Therapy (UDT) consisting of either diet, oral hypoglycemic agents (OHA's, no more than 2), or insulin (with or without no more than 1 OHA) plus either Placebo or Cycloset:

1. Whether add-on therapy with Cycloset results in all-cause rate of serious adverse events, which are not higher than add-on therapy with Placebo.

2. Whether add-on therapy with Cycloset results in disease-specific rate of serious cardiovascular adverse events, which are not higher than add-on therapy with Placebo.

While the primary purpose of this study is to establish the safety profile of Cycloset in type 2 diabetes, any potential positive cardiovascular benefits will be evaluated as well.

Other clinical measures:

3. The impact (either positive or negative) of Cycloset on HbA1c, fasting plasma glucose, weight, triglycerides lipids, blood pressure and patient tolerability after 12 months of therapy.

Furthermore, Hba1c changes from baseline to 24 weeks between Cycloset and Placebo among subjects with a baseline Hba1c of >= 7.5% among the following subgroups:

A. Treated at baseline with any Oral hypoglycemic agent (OHA) including injectable insulin secretagogues B. Metformin plus or minus one OHA or injectable insulin secretagogue C.

Sulphonylurea plus or minus one OHA or injectable insulin secretagogue D. Treated at baseline with Metformin and one sulphonylurea

Intervention(s) in this Clinical Trial

• Drug: Cycloset
  • quick release formulation of bromocriptine, 0.8 mg taken orally once daily in the am

Primary Measures

• Whether add-on therapy with Cycloset results in all-cause rate of serious adverse events, which are not higher than add-on therapy with Placebo.

Secondary Measures

• Whether add-on therapy with Cycloset results in disease-specific rate of serious cardiovascular adverse events, which are not higher than add-on therapy with Placebo.
• The impact (either positive or negative) of Cycloset on HbA1c, fasting plasma glucose, weight, triglycerides lipids, blood pressure and patient tolerability after 12 months of therapy.

Inclusion Criteria:

• Diagnosis of type 2 diabetes mellitus for at least six months, ages 30-80 years,stable diabetes therapy for at least 4 weeks either diet, no more than 2 oral hypoglycemic agents and/ or insulin,HbA1c < 10% for 12 weeks,Body Mass Index < 42,signed informed consent

Exclusion Criteria:

• Use of prescription sympathomimetic drugs within seven days, history of alcoholism or drug abuse in the previous three years,known allergy to the study drug,experimental drug or device use in the previous 30 days,pregnancy or lactation, blood donation in the previous 30 days,clinically significant major organ system disease, such as seizure disorder, significant gastroparesis,orthostatic hypotension, cerebrovascular accident in the previous 6 months, uncontrolled hypertension,coronary artery bypass graft or coronary angioplasty in the previous 3 months, myocardial infarction in the previous 6 months,unstable angina pectoris within the previous 3 months, congestive heart failure defined by NYHA as Class III or IV, clinical nephrotic syndrome,renal impairment with a serum creatinine ≥ 1.4 mg/dl, impaired liver function, including having AST or ALT greater than three times the upper limit of normal, active infection or a history of severe infection during the 30 days prior to screening, major surgical operation during the 30 days prior to screening, cancer, other than non-melanoma skin cancer within the past 5 years,any concurrent illness, other than diabetes mellitus, not controlled by a stable therapeutic regimen, working rotating or varying shifts,unapproved herbal supplements that may be associated with a risk of cardiovascular events,patients who have started therapy with an erectile dysfunction drug within 2 weeks prior to screening, circumstances or abnormalities that would interfere with the interpretation of safety or efficacy data or completion of the study, clinically significant abnormalities on screening central laboratory evaluation unless discussed with and approved by the principal investigator

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: VeroScience

Overall Clinical Trial Officials and Contacts

Michael Gaziano Principal Investigator MAVERIC  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00377676

Study ID Number: 165-AD-04-03-US-1

ClinicalTrials.gov Identifier: NCT00377676

Health Authority: United States: Food and Drug Administration