Chronic Lymphocytic Leukemia (CLL) in dogs represents an unmet veterinary need. The
literature reports a response rate of 70% to protocols using vincristine, prednisone, and
chlorambucil combinations; with chlorambucil as the maintenance drug. However, despite
therapy for CLL being generally rewarding, the mainstay treatment, chlorambucil, is not an
FDA approved drug for veterinary use. Presently, chlorambucil licensed for human use is
being used off-label, however currently available tablet sizes, 2 mg, of chlorambucil present a
challenge for treating dogs at standard prescribed dosages. Due to this challenge, unregulated
compounded chlorambucil products, with reports of varying potency and stability, are in wide
use in veterinary care with increased risk to the animal population, as well as the owners,
pharmacists, and the veterinarians handling these compounded products. As a result, there is
a clinical need for a veterinary specific chlorambucil product, developed and manufactured to
the highest quality and safety standards, and at the appropriate strength to facilitate accurate
dosing in small animals.
Chlorambucil 1 mg tablets are being developed to address the limitations of the 2 mg tablets
licensed for human use. This product is a Minor Use and Minor Species (MUMS) designated
investigational product that is eligible for conditional approval. The proposed study will
contribute to completing the requirements of the safety technical section for the designated
intended use in dogs with CLL. The safety of chlorambucil 1 mg tablets for the treatment of
CLL has been previously established in a target animal safety study using the reference
product. This bioavailability study is designed to evaluate the in vivo comparability of two
formulations, termed test and reference, of chlorambucil 1 mg tablets in healthy dogs thereby
enabling bridging of the previously established safety information of the reference product to
the test product. This study will be a randomised, non-terminal GLP (Good Laboratory
Practices) study in purpose-bred beagle dogs. The primary outcome variables will be AUC(0-t)
and Cmax.