Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure

Norah A. Terrault, Tarek Hassanein, Charles D. Howell, Shobha Joshi, John Lake, Linda Sher, Hugo E Vargas, Joe McIntosh, Shande Tang, Tim M. Jenkins

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background & Aims This is a phase II multicentre study to investigate the efficacy and safety of avatrombopag (E5501), an investigational second-generation thrombopoietin receptor agonist, administered one week prior to elective procedures in patients with thrombocytopenia secondary to cirrhosis. Methods Adults with cirrhosis and platelet counts ≥10 to ≤58 × 109/L were randomized to placebo or avatrombopag in two sequential cohorts. Cohort A: placebo vs. one of 3 different doses (100 mg loading dose followed by 20, 40, or 80 mg/day on days 2-7) of a first-generation avatrombopag formulation. Cohort B: placebo vs. one of 2 different doses (80 mg loading dose followed by 10 mg/day for days 2-7, or 20 mg/day for days 2-4) of a second-generation avatrombopag formulation. Primary end point was achievement of a platelet increase of ≥20 × 109/L from baseline and >50 × 109/L at least once during days 4-8. Results A total of 130 patients were randomized: 93 patients (51, cohort A; 42, cohort B) to avatrombopag and 37 (16, cohort A; 21 cohort B) to placebo. The primary end point was achieved by 49.0% of treated patients in cohort A and 47.6% in cohort B compared to 6.3% and 9.5% of controls; a dose response was seen. Each avatrombopag regimen had a higher proportion of responders compared with their respective cohort placebo arms (p <0.01), except for the 100/40 mg group in cohort A (p = 0.17). The most common adverse events were nausea, fatigue, and headache. One patient in the (100/80) avatrombopag group, without a Doppler assessment at screening was diagnosed with portal vein thrombosis during post-treatment follow-up. Conclusions In this study avatrombopag was generally well-tolerated and increased platelet counts in patients with cirrhosis undergoing elective invasive procedures.

Original languageEnglish (US)
Pages (from-to)1253-1259
Number of pages7
JournalJournal of Hepatology
Volume61
Issue number6
DOIs
StatePublished - Dec 1 2014

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Fibrosis
Placebos
Platelet Count
Thrombopoietin Receptors
1-(3-chloro-5-((4-(4-chloro-2-thienyl)-5-(4-cyclohexylpiperazin-1-yl)thiazol-2-yl)carbamoyl)-2-pyridyl)piperidine-4-carboxylic acid
Portal Vein
Thrombocytopenia
Nausea
Multicenter Studies
Fatigue
Headache
Thrombosis
Blood Platelets
Safety

Keywords

  • Avatrombopag
  • Chronic liver disease
  • Cirrhosis
  • Elective procedure
  • Platelet
  • Thrombocytopenia
  • Thrombopoietin receptor agonist

ASJC Scopus subject areas

  • Hepatology

Cite this

Terrault, N. A., Hassanein, T., Howell, C. D., Joshi, S., Lake, J., Sher, L., ... Jenkins, T. M. (2014). Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure. Journal of Hepatology, 61(6), 1253-1259. https://doi.org/10.1016/j.jhep.2014.07.007

Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure. / Terrault, Norah A.; Hassanein, Tarek; Howell, Charles D.; Joshi, Shobha; Lake, John; Sher, Linda; Vargas, Hugo E; McIntosh, Joe; Tang, Shande; Jenkins, Tim M.

In: Journal of Hepatology, Vol. 61, No. 6, 01.12.2014, p. 1253-1259.

Research output: Contribution to journalArticle

Terrault, NA, Hassanein, T, Howell, CD, Joshi, S, Lake, J, Sher, L, Vargas, HE, McIntosh, J, Tang, S & Jenkins, TM 2014, 'Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure', Journal of Hepatology, vol. 61, no. 6, pp. 1253-1259. https://doi.org/10.1016/j.jhep.2014.07.007
Terrault, Norah A. ; Hassanein, Tarek ; Howell, Charles D. ; Joshi, Shobha ; Lake, John ; Sher, Linda ; Vargas, Hugo E ; McIntosh, Joe ; Tang, Shande ; Jenkins, Tim M. / Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure. In: Journal of Hepatology. 2014 ; Vol. 61, No. 6. pp. 1253-1259.
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abstract = "Background & Aims This is a phase II multicentre study to investigate the efficacy and safety of avatrombopag (E5501), an investigational second-generation thrombopoietin receptor agonist, administered one week prior to elective procedures in patients with thrombocytopenia secondary to cirrhosis. Methods Adults with cirrhosis and platelet counts ≥10 to ≤58 × 109/L were randomized to placebo or avatrombopag in two sequential cohorts. Cohort A: placebo vs. one of 3 different doses (100 mg loading dose followed by 20, 40, or 80 mg/day on days 2-7) of a first-generation avatrombopag formulation. Cohort B: placebo vs. one of 2 different doses (80 mg loading dose followed by 10 mg/day for days 2-7, or 20 mg/day for days 2-4) of a second-generation avatrombopag formulation. Primary end point was achievement of a platelet increase of ≥20 × 109/L from baseline and >50 × 109/L at least once during days 4-8. Results A total of 130 patients were randomized: 93 patients (51, cohort A; 42, cohort B) to avatrombopag and 37 (16, cohort A; 21 cohort B) to placebo. The primary end point was achieved by 49.0{\%} of treated patients in cohort A and 47.6{\%} in cohort B compared to 6.3{\%} and 9.5{\%} of controls; a dose response was seen. Each avatrombopag regimen had a higher proportion of responders compared with their respective cohort placebo arms (p <0.01), except for the 100/40 mg group in cohort A (p = 0.17). The most common adverse events were nausea, fatigue, and headache. One patient in the (100/80) avatrombopag group, without a Doppler assessment at screening was diagnosed with portal vein thrombosis during post-treatment follow-up. Conclusions In this study avatrombopag was generally well-tolerated and increased platelet counts in patients with cirrhosis undergoing elective invasive procedures.",
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AU - Terrault, Norah A.

AU - Hassanein, Tarek

AU - Howell, Charles D.

AU - Joshi, Shobha

AU - Lake, John

AU - Sher, Linda

AU - Vargas, Hugo E

AU - McIntosh, Joe

AU - Tang, Shande

AU - Jenkins, Tim M.

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N2 - Background & Aims This is a phase II multicentre study to investigate the efficacy and safety of avatrombopag (E5501), an investigational second-generation thrombopoietin receptor agonist, administered one week prior to elective procedures in patients with thrombocytopenia secondary to cirrhosis. Methods Adults with cirrhosis and platelet counts ≥10 to ≤58 × 109/L were randomized to placebo or avatrombopag in two sequential cohorts. Cohort A: placebo vs. one of 3 different doses (100 mg loading dose followed by 20, 40, or 80 mg/day on days 2-7) of a first-generation avatrombopag formulation. Cohort B: placebo vs. one of 2 different doses (80 mg loading dose followed by 10 mg/day for days 2-7, or 20 mg/day for days 2-4) of a second-generation avatrombopag formulation. Primary end point was achievement of a platelet increase of ≥20 × 109/L from baseline and >50 × 109/L at least once during days 4-8. Results A total of 130 patients were randomized: 93 patients (51, cohort A; 42, cohort B) to avatrombopag and 37 (16, cohort A; 21 cohort B) to placebo. The primary end point was achieved by 49.0% of treated patients in cohort A and 47.6% in cohort B compared to 6.3% and 9.5% of controls; a dose response was seen. Each avatrombopag regimen had a higher proportion of responders compared with their respective cohort placebo arms (p <0.01), except for the 100/40 mg group in cohort A (p = 0.17). The most common adverse events were nausea, fatigue, and headache. One patient in the (100/80) avatrombopag group, without a Doppler assessment at screening was diagnosed with portal vein thrombosis during post-treatment follow-up. Conclusions In this study avatrombopag was generally well-tolerated and increased platelet counts in patients with cirrhosis undergoing elective invasive procedures.

AB - Background & Aims This is a phase II multicentre study to investigate the efficacy and safety of avatrombopag (E5501), an investigational second-generation thrombopoietin receptor agonist, administered one week prior to elective procedures in patients with thrombocytopenia secondary to cirrhosis. Methods Adults with cirrhosis and platelet counts ≥10 to ≤58 × 109/L were randomized to placebo or avatrombopag in two sequential cohorts. Cohort A: placebo vs. one of 3 different doses (100 mg loading dose followed by 20, 40, or 80 mg/day on days 2-7) of a first-generation avatrombopag formulation. Cohort B: placebo vs. one of 2 different doses (80 mg loading dose followed by 10 mg/day for days 2-7, or 20 mg/day for days 2-4) of a second-generation avatrombopag formulation. Primary end point was achievement of a platelet increase of ≥20 × 109/L from baseline and >50 × 109/L at least once during days 4-8. Results A total of 130 patients were randomized: 93 patients (51, cohort A; 42, cohort B) to avatrombopag and 37 (16, cohort A; 21 cohort B) to placebo. The primary end point was achieved by 49.0% of treated patients in cohort A and 47.6% in cohort B compared to 6.3% and 9.5% of controls; a dose response was seen. Each avatrombopag regimen had a higher proportion of responders compared with their respective cohort placebo arms (p <0.01), except for the 100/40 mg group in cohort A (p = 0.17). The most common adverse events were nausea, fatigue, and headache. One patient in the (100/80) avatrombopag group, without a Doppler assessment at screening was diagnosed with portal vein thrombosis during post-treatment follow-up. Conclusions In this study avatrombopag was generally well-tolerated and increased platelet counts in patients with cirrhosis undergoing elective invasive procedures.

KW - Avatrombopag

KW - Chronic liver disease

KW - Cirrhosis

KW - Elective procedure

KW - Platelet

KW - Thrombocytopenia

KW - Thrombopoietin receptor agonist

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