Safety and Tolerability Study of Cycloset in Treatment of Type 2 Diabetes

NCT00377676 | Completed Phase 3 Results DMC

• 1 other identifier: 165-AD-04-03-US-1
• Study Type: interventional
• Target: 3,095
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

diabetes; diabetes mellitus

Outcome Measures

Primary Outcomes (1)

• Subjects Experiencing Serious Adverse Events

  Number of subjects reporting all-cause Serious Adverse Events (SAEs) for usual drug therapy plus Cycloset vs. that for usual drug therapy (UDT) plus placebo from baseline to week 52.

  From baseline to week 52.

Secondary Outcomes (3)

• Number of Subjects Experiencing Serious Cardiovascular Adverse Events

  Baseline to week 52.

• Change in HbA1c From Baseline to Week 24 in Subjects Failing Treatment With Metformin Plus a Sulfonylurea

  Baseline to week 24

• Change in HbA1c From Baseline to Week 24 for Subjects With a Baseline HbA1c of ≥ 7.5% Who Were Taking at Least One Oral Hypoglycemia Agent (OHA) at Baseline.

  Baseline to week 24

Study Arms (2)

Usual Diabetes Therapy plus placebo

EXPERIMENTAL

Usual diabetes therapy plus placebo

Drug: Usual Diabetes Therapy plus placebo

Drug Cycloset

EXPERIMENTAL

Drug: Cycloset

Interventions

Cycloset DRUG

Usual diabetes therapy plus Cycloset

Also known as: bromocriptine mesylate

Drug Cycloset

Usual Diabetes Therapy plus placebo DRUG

Placebo tablet taken orally once in the morning, beginning with one tablet daily, titrated up by 1 tablet each week to a maximum of 6 tablets daily

Also known as: placebo

Usual Diabetes Therapy plus placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes
• age 30-80 years
• body mass index \< 43 kg/m2
• HbA1c ≤ 10% for at least 12 weeks prior to screening
• stable diabetes therapeutic regimen consisting of either diet, oral hypoglycemic agents (no more than 2), or insulin (with or without no more than 1 oral hypoglycemic agent) for 4 weeks prior to randomization

You may not qualify if:

• Subject who had taken prescription sympathomimetic drugs within seven (7) days prior to the first screening visit. Prescription sympathomimetic drugs were not allowed for any period greater than ten (10) consecutive days during the course of the study. Other ergot alkaloid derivatives or anti-migraine medications such as zolmitriptan (Zomig) and sumatriptan (Imitrex) were not permitted during the study.
• Subject who had a history of alcoholism or drug abuse in the three (3) years prior to the first screening visit.
• Subject who had a known hypersensitivity to any of the formulation components of the study drug.
• Subject who had received any experimental drug or used an experimental device in the 30 days prior to the first screening visit or would do so during the study.
• Subject who was pregnant or lactating women or women planning to become pregnant during the study. Women of childbearing potential had to have a negative pregnancy test at screening. Women who became pregnant were discontinued from the study.
• Subject who had given donations of blood during the 30 days prior to the screening visit. Donation of blood also was prohibited during the study and for 30 days after completion of the study.
• Subjects with clinically significant major organ system disease, such as
• seizure disorder
• significant gastroparesis or orthostatic hypotension (autonomic neuropathy)
• cerebrovascular accident in the previous 6 months
• uncontrolled hypertension (systolic BP \>160 or diastolic BP \> 100 at screening)
• coronary artery bypass graft or coronary angioplasty in the previous 3 months, myocardial infarction in the previous 6 months, or unstable angina pectoris (chest pain at rest, worsening chest pain, or admission to the ER or hospital for chest pain) within the previous 3 months
• congestive heart failure defined by NYHA as Class III or IV
• clinical nephrotic syndrome, or renal impairment with a serum creatinine \> 1.4 mg/dl if female receiving treatment with metformin, \> 1.5 mg/dl if male receiving treatment with metformin, and \> 1.6 mg/dl in not on metformin
• impaired liver function, including having AST or ALT greater than three times the upper limit of normal

Sponsors & Collaborators

• VeroScience: lead

Related Publications (6)

• 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. doi: 10.1186/1472-6823-7-3.

  PMID: 17592632 BACKGROUND

• Gaziano JM, Cincotta AH, O'Connor CM, Ezrokhi M, Rutty D, Ma ZJ, Scranton RE. Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes. Diabetes Care. 2010 Jul;33(7):1503-8. doi: 10.2337/dc09-2009. Epub 2010 Mar 23.

  PMID: 20332352 RESULT

• Chamarthi B, Cincotta AH. Effect of bromocriptine-QR therapy on glycemic control in subjects with type 2 diabetes mellitus whose dysglycemia is inadequately controlled on insulin. Postgrad Med. 2017 May;129(4):446-455. doi: 10.1080/00325481.2017.1315290. Epub 2017 Apr 12.

  PMID: 28374645 DERIVED

• Chamarthi B, Ezrokhi M, Rutty D, Cincotta AH. Impact of bromocriptine-QR therapy on cardiovascular outcomes in type 2 diabetes mellitus subjects on metformin. Postgrad Med. 2016 Nov;128(8):761-769. doi: 10.1080/00325481.2016.1243003. Epub 2016 Oct 11.

  PMID: 27687032 DERIVED

• Chamarthi B, Gaziano JM, Blonde L, Vinik A, Scranton RE, Ezrokhi M, Rutty D, Cincotta AH. Timed Bromocriptine-QR Therapy Reduces Progression of Cardiovascular Disease and Dysglycemia in Subjects with Well-Controlled Type 2 Diabetes Mellitus. J Diabetes Res. 2015;2015:157698. doi: 10.1155/2015/157698. Epub 2015 Apr 28.

  PMID: 26060823 DERIVED

• Gaziano JM, Cincotta AH, Vinik A, Blonde L, Bohannon N, Scranton R. Effect of bromocriptine-QR (a quick-release formulation of bromocriptine mesylate) on major adverse cardiovascular events in type 2 diabetes subjects. J Am Heart Assoc. 2012 Oct;1(5):e002279. doi: 10.1161/JAHA.112.002279. Epub 2012 Oct 25.

  PMID: 23316290 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Bromocriptine

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Ergotamines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Ergolines; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Thus HbA1c was only performed on a subset of patients defined as failing (HbA1c \>= 7.5) and who were on oral diabetes medications. Forced titration of study drug may have lead to a greater number of discontinuations.

Results Point of Contact

• Title: Richard Scranton
• Organization: VeroScience

richard_scranton@veroscience.com

401 816-0525

Study Officials

• Michael Gaziano

  MAVERIC

  PRINCIPAL INVESTIGATOR

• Richard E Scranton, MD MPH

  VeroScience

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2006
• First Posted: September 18, 2006
• Study Start: July 1, 2004
• Primary Completion: January 1, 2007
• Study Completion: January 1, 2007
• Last Updated: June 10, 2016
• Results First Posted: October 28, 2011

Record last verified: 2016-05