Bromocriptine-QR Therapy on Sympathetic Tone and Vascular Biology in Type 2 Diabetes Subjects

This is an interventional treatment trial for Diabetic Autonomic Neuropathy Read More

Inclusion Criteria:

• Type 2 diabetes subjects between the ages of 30 and 80 years of age, inclusive, at Screening
• Hemoglobin A1c (HbA1c) ≤10.0% at screening
• Male or female (female of child bearing age must use definitive contraceptive therapy)
• Type 2 Diabetes Mellitus subjects on a stable anti-diabetes regimen of diet and/or metformin alone therapy or on metformin plus an insulin secretion enhancer (sulfonylureas, dipeptidyl peptidase 4 (DPP4) Inhibitors, Glucagon-like peptide (GLP-1) analogs) therapy for a 60 day period prior to randomization. Subjects with diabetes duration of ≥ 4 years must be using an insulin secretion enhancer (e.g. sulphonylureas (SU), DPP4, GLP-1 analog). Subjects must have a documented C-peptide level (either fasting or random) of >2 ng/ml from the screening visit.

Exclusion Criteria:

• Presence of type 1 diabetes mellitus (defined as C-peptide <1 ng /ml)
• Type 2 diabetes mellitus subjects on insulin.
• Use of prescription sympathomimetics, ergot alkaloid derivatives, or anti-migraine medications, dopamine2 (D2)-like receptor antagonists (e.g. metoclopramide, domperidone) or systemic corticosteroids
• Uncontrolled hypertension (systolic BP >160 or diastolic BP > 100 at screening) or a history of orthostatic hypotension
• History of significant gastroparesis
• Presence of diabetic retinopathy that is more severe than "background" level
• Presence of diabetic nephropathy, or renal impairment defined by blood urea nitrogen (BUN) >40mg/dl and serum creatinine > 1.4 mg/dl if female taking metformin, >1.5 mg/dl. if male taking metformin, and >1.6 mg/dl if not taking metformin
• Presence of clinically significant peripheral or autonomic neuropathy that is clearly of non-diabetic origin
• History of major macrovascular events such as myocardial infarction or cerebrovascular event such as stroke within the past 6 months. Other exclusions include coronary artery bypass graft or coronary angioplasty in the previous 3 months, unstable angina pectoris (chest pain at rest, worsening chest pain, or admission to the emergency room or hospital for chest pain) within the previous 3 months, or seizure disorders.
• Active infection (e.g., human immunodeficiency virus (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
• Uncontrolled or untreated hypothyroidism as evidenced by thyroid stimulating hormone (TSH) concentrations >4.8 µU/ml
• Other serious medical conditions which, in the opinion of the investigator, would compromise the subject's participation in the study, including any concurrent illness, other than diabetes mellitus, not controlled by a stable therapeutic regimen, or conditions or abnormalities (e.g., blindness) that might interfere with interpretation of safety or efficacy data, or history of non-compliance
• Clinically significant abnormalities on screening laboratory evaluation, unless approved by the Sponsor
• Abnormalities of liver function defined as any liver enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum glutamic-pyruvic transaminase (SGPT), Serum glutamic oxaloacetic transaminase (SGOT) greater than 3 times the upper limit of normal
• History of New York Heart Association (NYHA) Class III-IV congestive heart failure.
• Concurrent participation in another clinical trial with use of an experimental drug or device within 30 days of study entry.
• History of alcohol or substance abuse or dementia
• Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening. Women who become pregnant will be discontinued from the study.
• Known hypersensitivity to any of the formulation components
• Working rotating, varying or night shifts
• Use of unapproved herbal supplements that may be associated with a risk of cardiovascular events (such as ephedra, yohimbe etc)
• Patients who have started therapy with an erectile dysfunction drug within 2 weeks prior to screening; patients may not begin treatment with an erectile dysfunction drug during the study period; patients currently taking erectile dysfunction drugs should do so only under medical supervision.
• Donation of blood in the previous 30 days. Blood donation is also not allowed during the study or for 30 days after completion of the study.