title: A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia.
abstract: Stimulation of platelet production by thrombopoietin-receptor agonists (TPO-RAs) is an effective second-line treatment in immune thrombocytopenia (ITP). This 28-day phase 2 study assigned subjects with ITP of ≥3 months to once-daily oral avatrombopag (2.5, 5, 10, or 20 mg), an investigational nonpeptide TPO-RA active in humans, or placebo; subjects completing randomized treatment could enroll in a 24-week extension study. Of 64 randomized subjects, 13% (avatrombopag 2.5 mg), 53% (5 mg), 50% (10 mg), and 80% (20 mg), vs 0% for placebo, achieved a platelet count (PC) response of ≥50 × 10(9)/L with ≥20 × 10(9)/L increase above baseline at day 28. Fifty-three subjects (83%) entered the extension: 52% and 76% had a durable (PC response at ≥75% of their platelet assessments over the last 14 weeks) and overall (stable response or response at any ≥2 consecutive visits) response, respectively. All subjects experienced ≥1 adverse event (AE) (most commonly fatigue, headache, and epistaxis); 19% (n = 12) reported ≥1 serious AE; 10 (16%) withdrew due to an AE (5 due to increased PC). Avatrombopag was active and generally well tolerated, with PC response rates and AE incidence comparable with other TPO-RAs. These studies were registered at www.clinicaltrials.gov as #NCT00441090 and #NCT00625443.
authors.affiliation: Division of Hematology, Departments of Pediatrics and Medicine, Weill Medical College of Cornell University, New York, NY;
authors.forename: James B
authors.initials: JB
authors.lastname: Bussel
authors.affiliation: Hematology Department, Massachusetts General Hospital, Boston, MA;
authors.forename: David J
authors.initials: DJ
authors.lastname: Kuter
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, NY;
authors.forename: Louis M
authors.initials: LM
authors.lastname: Aledort
authors.affiliation: Division of Coagulation, Georgetown University Medical Center, Washington, DC;
authors.forename: Craig M
authors.initials: CM
authors.lastname: Kessler
authors.affiliation: Department of Medicine and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Adam
authors.initials: A
authors.lastname: Cuker
authors.affiliation: Kansas City Cancer Center, Kansas City, MO; and.
authors.forename: Kelly B
authors.initials: KB
authors.lastname: Pendergrass
authors.affiliation: Eisai Corporation of North America, Woodcliff Lake, NJ.
authors.forename: Shande
authors.initials: S
authors.lastname: Tang
authors.affiliation: Eisai Corporation of North America, Woodcliff Lake, NJ.
authors.forename: Joe
authors.initials: J
authors.lastname: McIntosh
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004844:Epistaxis / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000473:pathology; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015507:Drugs, Investigational; D053628:Receptors, Thrombopoietin; D013844:Thiazoles; D013876:Thiophenes; C533238:avatrombopag