FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1996311003> ?p ?o ?g. }

• W1996311003 abstract "Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FLBackground: Biopharmaceutical and clinical pharmacology studies are typically conducted in healthy volunteers with few exceptions, such as for anti-cancer drugs. Traditional chemotherapies are too toxic to be studied in healthy volunteers. However, even for targeted anti-cancer drugs that often have mild to moderate toxicity profiles that don't expose healthy volunteers to extra risks, studies have rarely been conducted in the population. Navitoclax (ABT-263) is an orally bioavailable, targeted Bcl-2 family protein inhibitor that has been studied in several Phase 1 studies in cancer patients. The need to evaluate multiple formulations and the difficulty in recruiting patients made it critical to evaluate the possibility of recruiting healthy volunteers to support formulation development.Methods: Nonclinical safety data and clinical data from Phase 1 studies in cancer patients were evaluated extensively by a multi-functional team to determine the subject inclusion criteria, the maximally recommended dose, and a risk management plan. The protocol, safety evaluation and recommendations were reviewed and approved by the Drug Safety Evaluation Committee at Abbott.Results: In nonclinical studies, navitoclax was not genotoxic; it caused testicular toxicity, and dose-dependent thrombocytopenia (TCP) and lymphopenia, which are all expected from inhibition of Bcl-2 targets. In Phase 1 single-agent studies in cancer patients, the most frequent, dose-limiting toxicity was TCP. Nonclinical safety data supported a single dose ≤30 mg navitoclax in healthy volunteers. Furthermore, evaluation of clinical safety data, TCP dose-response and lymphopenia data supported administration of a navitoclax dose ≤100 mg in a single-dose, multiple-period crossover study in healthy female volunteers of non-childbearing potential. Two relative bioavailability (BA) studies in healthy female subjects with non-child bearing potential (N=12 each) were conducted sequentially and successfully, the first at a 25 mg dose and the second at a 100 mg dose. Compared to similar studies in cancer patients, on average, each study in healthy volunteers saved 3.5 months. A well-informed decision to select a Phase 2 formulation was made on the basis of limited data in patients and high-quality data in healthy volunteers.Conclusion: The case study illustrated that targeted anti-cancer drugs can be studied in healthy volunteers with careful assessment of both clinical/nonclinical data and by putting appropriate risk management plan in place. When feasible, BA studies in healthy volunteers avoid delaying potentially active treatments to cancer patients. Such studies also provide high-quality bioavailability data in a timelier and inexpensive fashion compared to similar studies in cancer patients, and they don't impose risks beyond the minimal levels that are standard in healthy volunteer studies.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2656. doi:10.1158/1538-7445.AM2011-2656" @default.
• W1996311003 created "2016-06-24" @default.
• W1996311003 creator A5012241694 @default.
• W1996311003 creator A5015092618 @default.
• W1996311003 creator A5016906085 @default.
• W1996311003 creator A5056954312 @default.
• W1996311003 creator A5059315880 @default.
• W1996311003 creator A5062887347 @default.
• W1996311003 creator A5087150838 @default.
• W1996311003 creator A5087268106 @default.
• W1996311003 date "2011-04-15" @default.
• W1996311003 modified "2023-09-27" @default.
• W1996311003 title "Abstract 2656: Ethical considerations in evaluating targeted anticancer drug candidates in healthy volunteers – safety and risk assessments" @default.
• W1996311003 doi "https://doi.org/10.1158/1538-7445.am2011-2656" @default.
• W1996311003 hasPublicationYear "2011" @default.
• W1996311003 type Work @default.
• W1996311003 sameAs 1996311003 @default.
• W1996311003 citedByCount "0" @default.
• W1996311003 crossrefType "proceedings-article" @default.
• W1996311003 hasAuthorship W1996311003A5012241694 @default.
• W1996311003 hasAuthorship W1996311003A5015092618 @default.
• W1996311003 hasAuthorship W1996311003A5016906085 @default.
• W1996311003 hasAuthorship W1996311003A5056954312 @default.
• W1996311003 hasAuthorship W1996311003A5059315880 @default.
• W1996311003 hasAuthorship W1996311003A5062887347 @default.
• W1996311003 hasAuthorship W1996311003A5087150838 @default.
• W1996311003 hasAuthorship W1996311003A5087268106 @default.
• W1996311003 hasConcept C121608353 @default.
• W1996311003 hasConcept C126322002 @default.
• W1996311003 hasConcept C143998085 @default.
• W1996311003 hasConcept C2776190711 @default.
• W1996311003 hasConcept C2780035454 @default.
• W1996311003 hasConcept C2908647359 @default.
• W1996311003 hasConcept C29730261 @default.
• W1996311003 hasConcept C535046627 @default.
• W1996311003 hasConcept C71924100 @default.
• W1996311003 hasConcept C98274493 @default.
• W1996311003 hasConcept C99454951 @default.
• W1996311003 hasConceptScore W1996311003C121608353 @default.
• W1996311003 hasConceptScore W1996311003C126322002 @default.
• W1996311003 hasConceptScore W1996311003C143998085 @default.
• W1996311003 hasConceptScore W1996311003C2776190711 @default.
• W1996311003 hasConceptScore W1996311003C2780035454 @default.
• W1996311003 hasConceptScore W1996311003C2908647359 @default.
• W1996311003 hasConceptScore W1996311003C29730261 @default.
• W1996311003 hasConceptScore W1996311003C535046627 @default.
• W1996311003 hasConceptScore W1996311003C71924100 @default.
• W1996311003 hasConceptScore W1996311003C98274493 @default.
• W1996311003 hasConceptScore W1996311003C99454951 @default.
• W1996311003 hasLocation W19963110031 @default.
• W1996311003 hasOpenAccess W1996311003 @default.
• W1996311003 hasPrimaryLocation W19963110031 @default.
• W1996311003 hasRelatedWork W185112251 @default.
• W1996311003 hasRelatedWork W1985969253 @default.
• W1996311003 hasRelatedWork W2005352733 @default.
• W1996311003 hasRelatedWork W2028688785 @default.
• W1996311003 hasRelatedWork W2066665319 @default.
• W1996311003 hasRelatedWork W2079720175 @default.
• W1996311003 hasRelatedWork W2112762770 @default.
• W1996311003 hasRelatedWork W2117666134 @default.
• W1996311003 hasRelatedWork W2150700051 @default.
• W1996311003 hasRelatedWork W2153389462 @default.
• W1996311003 hasRelatedWork W2343717137 @default.
• W1996311003 hasRelatedWork W2593572988 @default.
• W1996311003 hasRelatedWork W2597313064 @default.
• W1996311003 hasRelatedWork W2609906381 @default.
• W1996311003 hasRelatedWork W2751487137 @default.
• W1996311003 hasRelatedWork W2886344931 @default.
• W1996311003 hasRelatedWork W2980972214 @default.
• W1996311003 hasRelatedWork W3087306505 @default.
• W1996311003 hasRelatedWork W3202398210 @default.
• W1996311003 hasRelatedWork W3209995488 @default.
• W1996311003 isParatext "false" @default.
• W1996311003 isRetracted "false" @default.
• W1996311003 magId "1996311003" @default.
• W1996311003 workType "article" @default.