The FDA approved VeroScience’s Cycloset (bromocriptine mesylate) 0.8mg tablets on May 5 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
The NDA was first submitted in 1997 – before the 505(b)(2) guidance. The API, bromocriptine mesylate was approved under NDA 017962 in 1978 as Parlodel in 2.5 mg tablets and 5 mg capsules. Parlodel is indicated for hyperprolactinemia-associated dysfunctions, acromegaly and parkinson’s disease.
Cycloset was approved as a new formulation, so it was approved under 505(b)(2). But, while the formulation development was typical of a lot of 505(b)(2) projects, the clinical development was anything but small. The FDA issued a response letter in October 1999. Apparently, FDA was satisfied with the efficacy but safety had not been shown – per the Clinical Trials summary: “While Cycloset has demonstrated efficacy by reducing HbA1c, fasting and post-prandial glucose and fasting and post-prandial triglycerides, the relatively small numbers of individuals treated for type 2 diabetes during the controlled Phase III clinical trials of Cycloset did not allow for a full evaluation of the safety profile. Since persons with diabetes are already at higher risk for cardiovascular disease, it is important to examine more fully the spectrum of potential adverse or positive effects from Cycloset in a large sample of persons with diabetes.”
In the intervening several years, he company went though a number of changes and, in 2006 decided to run the 3000- patient Phase 3b trial referenced above. Those of you interested in diabetes drugs may know that last December, FDA issued a new guideline for the cardiovascular safety and that the new standards would be applied to any drug in review. This guidance came after VeroScience submitted the Phase 3b study. Apparently, the VeroScience study passed muster.
The Cycloset approval letter outlined how PREA would affect the drug. The Agency waived the pediatric study requirement for ages 0 to 9 (inclusive) because type 2 diabetes is rare in this population. FDA deferred pediatric studies for ages 10-16 years (inclusive). The 3 studies are:
Pediatric bioavailability study: To Assess the Safety, Tolerability and Pharmacokinetics of Cycloset in 10 to 16 year old Type 2 Diabetic Subjects
Pediatric feasibility study: A Randomized, Double-Blind, Controlled Study To Assess the Use and Effectiveness of Cycloset in Children Aged 10 to 16 With a Diagnosis of Type 2 Diabetes Mellitus
Clinical efficacy and safety study: A Pivotal, Randomized, Double-Blind, Controlled, Efficacy and Safety Study of the Use of Cycloset for the Treatment of Type 2 Diabetes Mellitus in Children Aged 10 — 16 years with a Diagnosis of Type 2 Diabetes Mellitus