title: Studying navitoclax, a targeted anticancer drug, in healthy volunteers--ethical considerations and risk/benefit assessments and management.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: AbbVie, Inc., North Chicago, IL, U.S.A. hao.xiong@abbvie.com.
authors: Hao
authors: H
authors: Xiong
authors: Alexion Pharmaceuticals, Inc., Cheshire, CT, U.S.A.
authors: Rajendra S
authors: RS
authors: Pradhan
authors: NeoStem, Inc., New York, NY, U.S.A.
authors: Adel
authors: A
authors: Nada
authors: Astellas Pharma Global Development, Inc., Northbrook, IL, U.S.A.
authors: Andrew P
authors: AP
authors: Krivoshik
authors: AbbVie, Inc., North Chicago, IL, U.S.A.
authors: Kyle D
authors: KD
authors: Holen
authors: AbbVie, Inc., North Chicago, IL, U.S.A.
authors: James W
authors: JW
authors: Rhodes
authors: AbbVie, Inc., North Chicago, IL, U.S.A.
authors: Gary B
authors: GB
authors: Gordon
authors: AbbVie, Inc., North Chicago, IL, U.S.A.
authors: Rod
authors: R
authors: Humerickhouse
authors: AbbVie, Inc., North Chicago, IL, U.S.A.
authors: Walid M
authors: WM
authors: Awni
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000814:Aniline Compounds / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001682:Biological Availability; D001702:Biopharmaceutics / Q000941:ethics* / Q000379:methods; D015331:Cohort Studies; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D018570:Risk Assessment; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D013449:Sulfonamides; C528561:navitoclax
keywords: Bcl-2 inhibitor; Navitoclax; healthy volunteers; phase 1 clinical trials; safety risk evaluation and management