Safety and Tolerability Study of Cycloset in Treatment of Type 2 Diabetes - Full Text View

Sponsored by:	VeroScience
Information provided by:	VeroScience
ClinicalTrials.gov Identifier:	NCT00377676

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: Cycloset	Phase III

MedlinePlus related topics: Diabetes

Drug Information available for: Bromocriptine Bromocriptine mesylate

U.S. FDA Resources

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

Further study details as provided by VeroScience:

Primary Outcome 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 Outcome 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.

Estimated Enrollment:	3000
Study Start Date:	July 2004
Study Completion Date:	December 2006

Intervention Details:

quick release formulation of bromocriptine, 0.8 mg taken orally once daily in the am

Detailed Description:

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:

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.
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:
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

Eligibility

Ages Eligible for Study:	30 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00377676

Sponsors and Collaborators

VeroScience

Investigators

Principal Investigator:	Michael Gaziano	MAVERIC
Principal Investigator:	Richard E Scranton, MD MPH	VeroScience

More Information

Publications:

Scranton RE, Gaziano JM, Rutty D, Ezrokhi M, Cincotta A. 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. BMC Endocr Disord. 2007 Jun 25;7:3.

Responsible Party:	Verosicence ( Richard Scranton MD MPH Chief Medical Officer )
Study ID Numbers:	165-AD-04-03-US-1
Study First Received:	September 14, 2006
Last Updated:	June 24, 2008
ClinicalTrials.gov Identifier:	NCT00377676
Health Authority:	United States: Food and Drug Administration

Keywords provided by VeroScience:

diabetes
diabetes mellitus

Study placed in the following topic categories:

Bromocriptine
Dopamine
Metabolic Diseases
Diabetes Mellitus, Type 2
Diabetes Mellitus

Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders

Additional relevant MeSH terms:

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Hormone Antagonists
Therapeutic Uses
Physiological Effects of Drugs

Hormones, Hormone Substitutes, and Hormone Antagonists
Antiparkinson Agents
Dopamine Agents
Dopamine Agonists
Central Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009