TY - JOUR T1 - Studying Navitoclax, a Targeted Anticancer Drug, in Healthy Volunteers – Ethical Considerations and Risk/Benefit Assessments and Management JF - Anticancer Research JO - Anticancer Res SP - 3739 LP - 3746 VL - 34 IS - 7 AU - HAO XIONG AU - RAJENDRA S. PRADHAN AU - ADEL NADA AU - ANDREW P. KRIVOSHIK AU - KYLE D. HOLEN AU - JAMES W. RHODES AU - GARY B. GORDON AU - ROD HUMERICKHOUSE AU - WALID M. AWNI Y1 - 2014/07/01 UR - http://ar.iiarjournals.org/content/34/7/3739.abstract N2 - Background: Biopharmaceutical studies for anti-cancer drugs are typically conducted in cancer patients due to unacceptable toxicities to healthy volunteers. Navitoclax is a first-in-class, orally bioavailable, targeted Bcl-2 family protein inhibitor that has been studied in cancer patients. Methods: A strategy that integrated the evaluation of non-clinical toxicology data and clinical data in cancer patients was employed to assess the feasibility, determine doses and establish risk management plans for studying navitoclax in healthy volunteers. Two relative bioavailability/food effect studies with either a 25 mg dose or 50 and 100 mg doses of navitoclax were conducted sequentially in healthy female volunteers of non-childbearing potential. Results/Conclusion: Navitoclax was well-tolerated in both studies in healthy volunteers, and did not impose risks beyond the minimal levels expected in healthy volunteer studies. Compared to a similar study in cancer patients, the studies in healthy volunteers generated higher quality data in a short period of time to support formulation selection. ER -