Pharmacokinetic Study of CYCLOSET ® 0.8 mg Tablets in Children and Adolescent Type 2 Diabetes Mellitus Subjects

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.

The study is a multi-center, single dose, open-label, 1-period design. Thirty (30) patients will be enrolled in the study and at least twenty-four (24) patients are expected to complete the study. Male and female patients with confirmed Type 2 Diabetes, non-or ex-smokers, aged 10 to less than 18 years will be selected according to the inclusion and exclusion criteria. Patients will be admitted to the clinical site at least 10 hours prior to drug administration which will occur within 2 hours of waking on the morning of Day 2. Ondansetron hydrochloride will be administered orally, approximately 6 hours before the dosing time of Cycloset (bromocriptine mesylate). Subjects weighing 50 to 60 kg will receive 6mg ondansetron hydrochloride (liquid 7.5 ml) and subjects weighing ≥60 kg will receive ondansetron hydrochloride 8 mg (liquid 10 ml). A single, weight-adjusted dose of CYCLOSET (bromocriptine mesylate), of approximately 0.048 mg/kg, will be administered orally with 240 mL of water in the morning, after a 10-hour overnight fast, and thirty minutes after the start of a standardized breakfast that meets American Diabetes Association diet recommendations. On day 2, after a supervised overnight fast, the patients will be awakened, vital signs (blood pressure, pulse rate and body temperature) will be measured and the first blood sample (T= 0) will be collected. Seventeen (17) blood samples will be collected for pharmacokinetic sampling at 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours post drug administration. Finger sticks for blood glucose levels will be obtained every hour for the first 4 hours following administration of bromocriptine mesylate, and then additionally as deemed necessary by the study physician. Safety will be evaluated through the assessment of adverse events and laboratory tests and vital signs.