Tuberculosis (TB) is an insidious disease that kills between 1.5?2.0 million people annually. The increase in multiple and extensively drug-resistant TB globally presents an urgent unmet medical need that is underserved by the pace of new drug and vaccine development. Following a decade of research activity, CPZEN-45, a caprazamycin derivative, has been shown to be safe and efficacious when administered via both the subcutaneous and pulmonary routes in animals. The pulmonary route of administration is more desirable than subcutaneous delivery because it is non-invasive and more acceptable to the severely compromised target patient population. CPZEN-45 is poised for development in formal preclinical and initial clinical studies. It is proposed that in supporting scale up and technical transfer to a current Good Manufacturing Practice (cGMP) manufacturing facility, the performance of current Good Laboratory Practice (cGLP) preclinical toxicology studies and preparation of Investigational New Drug (IND) Application documents to support a Phase I single-dose escalating tolerability study would meet U.S. Food and Drug Administration (FDA) requirements for product approval. The experiments required to complete the IND materials are as follows:
Specific Aim 1 ?Scale up and technical transfer of spray dried CPZEN-45 (scale up, technical transfer to a cGMP environment, development of validated analytical methods);
Specific Aim 2 ? cGMP rat and dog 14-day toxicology studies (aerosol characterization, rat and dog studies, validated bioanalytical methods);
Specific Aim 3 ?Document preparation and project management to support pre-IND meeting with the FDA (chemistry, manufacturing, and controls; data management; preclinical toxicology studies; data management, Phase I?Protocol development; single-dose escalation study of tolerability and pharmacokinetics).
Tuberculosis (TB) is an insidious disease that kills between 1.5?2.0 million people annually. The increase in multiple and extensively drug-resistant TB globally presents an urgent unmet medical need that is underserved by the pace of new drug and vaccine development. CPZEN-45, a caprazamycin derivative, is poised for development in formal preclinical and initial clinical studies. It is proposed that in supporting scale up and technical transfer to a current Good Manufacturing Practice (cGMP) manufacturing facility, the performance of current Good Laboratory Practice (cGLP) preclinical toxicology studies and preparation of pre-Investigational New Drug application documents to support a Phase I single-dose escalating tolerability study would meet U.S. Food and Drug Administration requirements for product approval.
