Intervention: Bromocriptine Mesylate
Trial phase: Phase 4
SMILES: CC(C)CC1C(=O)N2CCCC2C2(O)OC(NC(=O)C3C=C4c5cccc6[nH]c(Br)c(c56)CC4N(C)C3)(C(C)C)C(=O)N12.CS(=O)(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 43
Group description: Subjects were randomized in a double blind 1:1 ratio to receive UDT (usual diabetes therapy) plus bromocriptine-QR. Following randomization subjects were titrated to the maximum tolerated dose of the study drug over a four-week period. During these first 4 weeks, the daily dose of the study drug was titrated up by one tablet (0.8 mg bromocriptine-QR) per day on a weekly basis until a maximal tolerated dose of at least two tablets (1.6 mg/day bromocriptine-QR) and no more than four tablets (3.2 mg/per day b-QR) was achieved. Subjects were maintained at their maximum tolerated dose of between two to four tablets per day (1.6 to 3.2 mg bromocriptine-QR per day) for the duration of the study (24 weeks). Subjects were evaluated at 4 weeks after randomization, at 12 weeks after randomization, and then at study end (week 24 or early termination).

Cycloset: Cycloset 1.6 -3.2 mg/day
Eligibility criteria:
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.