CLINICAL TRIALS PROFILE FOR CYCLOSET

All Clinical Trials for Cycloset

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00377676 ↗	Safety and Tolerability Study of Cycloset in Treatment of Type 2 Diabetes	Completed	VeroScience	Phase 3	2004-07-01	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.
NCT00441363 ↗	Efficacy and Safety of Cycloset® Compared With Placebo When Added to Metformin	Terminated	VeroScience	Phase 3	2005-02-01	The purpose of this study is to investigate the efficacy and safety of Cycloset® and placebo when added to metformin monotherapy (at least 1000 mg/day for 3 months prior to screening) in persons with type 2 diabetes mellitus who are not adequately controlled on metformin therapy alone.
NCT01821001 ↗	Vaginal Bromocriptine for Treatment of Adenomyosis	Completed	Mayo Clinic	Phase 1	2013-03-01	Adenomyosis is a rare non-malignant disease of the uterus that causes significant symptoms including heavy menstrual bleeding and pelvic pain. The only widely accepted treatment for adenomyosis is hysterectomy. The investigators will use a dopamine agonist, bromocriptine, as a therapy based on animal models of the disease and our prior clinical research to observe any objective improvement in the extent of the disease using Magnetic Resonance Imaging (MRI)and standard measurements for other gynecologic diseases to measure symptomatology.
NCT02078440 ↗	Pharmacokinetic Study of CYCLOSET ® 0.8 mg Tablets in Children and Adolescent Type 2 Diabetes Mellitus Subjects	Completed	VeroScience	Phase 1	2014-01-01	The objective of this study is to evaluate the relative bioavailability, and the rate and extent of absorption of bromocriptine in male and female children and adolescent Type 2 Diabetes Mellitus patients, aged 10 to less than 18, under fed conditions. It is undetermined if the pharmacokinetic profile of bromocriptine-QR in type 2 diabetes children aged 10- to less than 18 years differs appreciably from that in healthy adults. Bromocriptine is extensively metabolized by the liver (namely CYP3A4). Studies in children have demonstrated little difference in clearance among children over 10 years of age compared to adults (Blanco et al, 2000). However, differences in blood volumes or other factors may impart differences that could affect the pharmacokinetic properties of bromocriptine-QR. Therefore, this study will assess the pharmacokinetics in children aged 10-to less than 18 years who have type 2 diabetes. After describing the profile of bromocriptine-quick release in this patient population, a follow on study will be conducted to evaluate its safety and efficacy in treating children and adolescents who have type 2 diabetes. The pharmacokinetic profile of bromocriptine will be determined following the administration of a single, weight-adjusted dose of CYCLOSET (bromocriptine mesylate) tablets. The study will be a single period, bioavailability study in 30 patients. The study duration will be 3 days.
NCT02133755 ↗	Effect of Bromocriptine on Insulin Resistance in Polycystic Ovarian Syndrome - A Pilot Study	Unknown status	IWK Health Centre	Phase 3	2014-07-01	The primary aim of this study is to determine the effect of dopamine agonist therapy on insulin resistance in lean vs. obese women with polycystic ovary syndrome. Polycystic ovary syndrome (PCOS) is a common metabolic abnormality in women. The diagnosis of PCOS relies on a constellation of symptoms and signs (problems with ovulation, clinical and/or biochemical signs of hyperandrogenism and cystic ovaries). Though not a diagnostic feature, insulin resistance (IR) is a hallmark of PCOS and up to 80% women with PCOS have IR. Although IR is more significant in obese women with PCOS, even lean women can be insulin resistant. No current therapy addresses the problem of insulin resistance in PCOS. Studies have suggested a dopamine deficiency in patients with PCOS, which may underlie the insulin resistance and may have a pathogenetic role in the development of PCOS. No study to date has assessed the impact of dopamine agonist therapy on IR in patients with PCOS.
NCT02299050 ↗	Effect of Cycloset on Glycemic Control When Added to Glucagon-like Peptide 1 (GLP-1) Analogue Therapy	Completed	VeroScience	Phase 4	2014-06-01	Purpose This study will examine the effect of the addition of Cycloset upon glucose metabolism (glycemic control including post prandial glucose metabolism) in individuals with inadequately controlled (HbA1c 7.5-10.0) type 2 diabetes (T2DM) who are already on Bydureon (exenatide once weekly) or Victoza (liraglutide once daily) as part of their standard care. Both a mechanistic rationale and empirical experimental evidence implicate a beneficial interaction between bromocriptine and the incretin mimetics (GLP-1 analogs) upon postprandial hyperglycemia in insulin resistant states. One of the actions of the incretin mimetics such as the GLP-1 analogs is to stimulate postprandial beta cell insulin secretory response to plasma glucose (see drug labeling information; www.fda.gov). Thus the combination of Cycloset that is working as a post prandial insulin sensitizier with therapies that increase post prandial insulin would be expected to provide complimentary glucose lowering effects. To date, however, no such studies investigating the interactive effects of a GLP-1 analog and Bromocriptine-QR (QR=extended release) (Cycloset) have been conducted in humans. Condition - Type 2 Diabetes. Intervention - Cycloset. Phase - Phase 4 Study Type: Interventional Study Design: Treatment, Single Group Assignment, Open Label, N/A, Safety/Efficacy Study Official Title: Effect of Cycloset on Glycemic Control in Type 2 Diabetic Patients Inadequately Controlled on GLP-1 Analogue Therapy

Clinical Trial Conditions for Cycloset

Condition Name

Condition Name for Cycloset
Intervention	Trials
Type 2 Diabetes	3
Type 2 Diabetes Mellitus	1
Adenomyosis	1
Dementia, Vascular	1

Condition MeSH

Condition MeSH for Cycloset
Intervention	Trials
Diabetes Mellitus, Type 2	4
Diabetes Mellitus	2
Cardiomyopathies	1
Diabetic Neuropathies	1

Clinical Trial Locations for Cycloset

Trials by Country

Trials by Country for Cycloset
Location	Trials
United States	9
Mexico	1
Canada	1

Trials by US State

Trials by US State for Cycloset
Location	Trials
Pennsylvania	2
Virginia	1
Texas	1
Missouri	1
Florida	1

Clinical Trial Progress for Cycloset

Clinical Trial Phase

Clinical Trial Phase for Cycloset
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	3
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for Cycloset
Clinical Trial Phase	Trials
Completed	5
Unknown status	1
Not yet recruiting	1

Clinical Trial Sponsors for Cycloset

Sponsor Name

Sponsor Name for Cycloset
Sponsor	Trials
VeroScience	4
Mayo Clinic	1
IWK Health Centre	1

Sponsor Type

Sponsor Type for Cycloset
Sponsor	Trials
Other	9
Industry	4
NIH	1

CYCLOSET: A Comprehensive Overview of Clinical Trials, Market Analysis, and Projections

Introduction to CYCLOSET

CYCLOSET, also known as bromocriptine mesylate, is a semi-synthetic alkaloid and an ergot derivative used in the management of type 2 diabetes. It is formulated as tablets for oral administration and is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

Clinical Trials Overview

The Cycloset Safety Trial (CST)

The Cycloset Safety Trial was a pivotal 52-week, double-blind, placebo-controlled study designed to investigate the overall and cardiovascular serious adverse event outcomes of CYCLOSET. Here are the key findings:

• Study Population: The trial included 3,070 patients, with a mean baseline age of 60 years (range 27-80) and 33% of the patients being 65 years or older. The mean baseline body mass index was 32 kg/m², and the mean duration of diabetes at baseline was 8 years with a mean baseline HbA1c of 7.0%[1][4].

• Dosage and Administration: Patients were treated with CYCLOSET titrated to 1.6 to 4.8 mg daily, as tolerated, within 2 hours of waking in the morning[1][4].

• Adverse Events: Common adverse events reported in ≥5% of patients included nausea, fatigue, vomiting, headache, and dizziness. These events were more likely to occur during the initial titration phase and were generally mild to moderate in severity[1][4].

• Cardiovascular Safety: The trial demonstrated that CYCLOSET was noninferior to placebo in terms of overall serious adverse event rates. Notably, CYCLOSET reduced the risk of the composite cardiovascular endpoint by 42% compared to placebo[4].

• Hypoglycemia and Syncope: The incidence of hypoglycemia was 6.9% among CYCLOSET-treated patients and 5.3% among placebo-treated patients. Syncope was reported in 1.6% of CYCLOSET-treated patients and 0.7% of placebo-treated patients[1].

Market Analysis

Market Trends and Drivers

The market for type 2 diabetes therapeutics is dynamic and influenced by several factors:

• Growing Demand: The global market for type 2 diabetes treatments is expanding, driven by the increasing prevalence of diabetes and the need for effective management options[2][3].

• Competitive Landscape: CYCLOSET competes in a market dominated by various classes of antidiabetic drugs, including GLP-1 therapies, insulin, and other oral antidiabetic agents. The competitive landscape is evolving with new entrants and combination products, such as Novo Nordisk’s IDegLira and Sanofi’s LixiLan[3].

• Regulatory Environment: Regulatory approvals and safety assessments play a crucial role. For instance, the European Medicines Agency (EMA) and the US FDA have investigated and cleared certain therapies, such as GLP-1 agonists, from any confirmed link to pancreatic cancer, which has stabilized their market position[3].

Sales Forecasts and Performance

• Historical Sales: Detailed historical sales data for CYCLOSET in major markets, including the US, EU5, and Japan, have been analyzed to understand its market performance. These analyses help in identifying trends and areas for growth[2].

• Future Projections: Sales forecasts for CYCLOSET from 2010 to 2020 have been provided in various reports, highlighting the drug’s potential in the market. These forecasts are based on factors such as efficacy, safety, pricing, and competition[2][5].

Market Characterization and Type 2 Diabetes Overview

Type 2 Diabetes Market

• Patient Population: The type 2 diabetes market is characterized by a large and growing patient population. In the US, EU5, and Japan, the patient demographics and treatment patterns have been extensively studied to understand market dynamics[2].

• Classification of Diabetes: Understanding the classification and evolution of anti-diabetic treatments is crucial for market analysis. Type 2 diabetes management has evolved significantly, with various therapeutic options available, each with its own efficacy and safety profile[2].

Cycloset’s Position in the Market

• Efficacy and Safety: CYCLOSET’s unique mechanism of action, involving the modulation of dopamine receptors, sets it apart from other antidiabetic drugs. Its safety profile, particularly the reduced risk of cardiovascular events, is a significant advantage in the market[1][4].

• Pricing and Competition: The pricing strategy for CYCLOSET and its competitive positioning against other antidiabetic medications are critical factors influencing its market performance. The drug’s ability to offer a unique benefit profile can help it maintain a competitive edge[2][5].

Contraindications and Warnings

Important Safety Information

• Hypersensitivity: CYCLOSET is contraindicated in patients with hypersensitivity to ergot-related drugs, bromocriptine, or any of the excipients in CYCLOSET[4].

• Syncopal Migraines: Patients with a history of syncopal migraines should not use CYCLOSET[4].

• Postpartum and Lactating Patients: The drug is contraindicated in postpartum patients and lactating women due to the risk of serious and life-threatening adverse reactions[4].

• Orthostatic Hypotension: CYCLOSET can cause orthostatic hypotension and syncope, particularly upon initiation or dose escalation. Patients taking antihypertensive medications should be monitored closely[4].

• Psychosis and Impulse Control Disorders: CYCLOSET may exacerbate psychotic disorders or reduce the effectiveness of drugs that treat psychosis. It is also associated with impulse control and compulsive behaviors, and its use in such patients is not recommended[4].

Drug Interactions

• Protein Binding: The active ingredient in CYCLOSET is highly bound to serum proteins, which may alter the effectiveness and risk for side effects of other highly protein-bound therapies when used concomitantly[1].

• Dopamine Antagonists: Concomitant use with dopamine antagonists, such as neuroleptic agents, is not recommended as it may diminish the effectiveness of both drugs[4].

Key Takeaways

• Clinical Safety: CYCLOSET has demonstrated a favorable safety profile, particularly in terms of cardiovascular events, in a large 52-week safety trial.
• Market Position: The drug competes in a dynamic market with a growing demand for effective type 2 diabetes treatments.
• Unique Mechanism: CYCLOSET’s mechanism of action, involving dopamine receptor modulation, offers a distinct benefit profile.
• Contraindications and Warnings: The drug has specific contraindications and warnings, including hypersensitivity, syncopal migraines, and potential for orthostatic hypotension.
• Drug Interactions: CYCLOSET may interact with other highly protein-bound therapies and dopamine antagonists, requiring careful management.

FAQs

What is CYCLOSET used for?

CYCLOSET (bromocriptine mesylate) is used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

What are the common adverse events associated with CYCLOSET?

Common adverse events include nausea, fatigue, vomiting, headache, and dizziness, which are generally mild to moderate in severity and more likely to occur during the initial titration phase[1][4].

Does CYCLOSET increase the risk of cardiovascular events?

No, CYCLOSET has been shown to reduce the risk of the composite cardiovascular endpoint by 42% compared to placebo in a 52-week safety trial[4].

Can CYCLOSET be used in patients with a history of syncopal migraines?

No, CYCLOSET is contraindicated in patients with a history of syncopal migraines[4].

How does CYCLOSET interact with other medications?

CYCLOSET may increase the unbound fraction of other highly protein-bound therapies and should not be used concomitantly with dopamine antagonists[1][4].

Sources

1. CYCLOSET® (bromocriptine mesylate tablets), for oral use. FDA.
2. Research and Markets: Cycloset (Type 2 Diabetes) - Analysis and Forecasts to 2020. Business Wire.
3. The Market for Type 2 Diabetes Therapeutics - Key Findings From a Recent Analysis of Global Drug Development Efforts. Drug Development.
4. Cycloset Clinical Profile. Veroscience.
5. Net Present Value Model: Cycloset. GlobalData.