Safety and Tolerability Study of Cycloset in Treatment of Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Cycloset; Usual Diabetes Therapy plus placebo
Intervention description: Usual diabetes therapy plus Cycloset; 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
Intervention MeSH terms: Bromocriptine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 3095.0
Sex: All
Minimum age: 30 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: diabetes; diabetes mellitus

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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

               -  active infection (e.g., HIV, hepatitis), 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 or non metastatic prostate cancer within the
                  past 5 years

               -  Any concurrent illness, other than diabetes mellitus, not controlled by a stable
                  therapeutic regimen

          -  Working rotating, varying or night shifts

          -  Patients taking unapproved herbal supplements that may be associated with a risk of
             cardiovascular events (such as ephedra, yohimbe etc)

          -  Patients who had started therapy with an erectile dysfunction drug within 2 weeks
             prior to screening; patients could not begin treatment with an erectile dysfunction
             drug during the study period; patients previously taking erectile dysfunction drugs
             could do so only under medical supervision.

          -  Subjects with circumstances or abnormalities (e.g., blindness or a history of
             non-compliance) that would interfere with the interpretation of safety or efficacy
             data or completion of the study.

          -  Clinically significant abnormalities (values outside the normal range) on screening
             central laboratory evaluation unless discussed with and approved by the study
             principal investigator or Sponsor medical monitor.