Is platelet monitoring during 7‐day lusutrombopag treatment necessary in chronic liver disease patients with thrombocytopenia undergoing planned invasive procedures? A phase IIIb open‐label study

Numata, Kazushi; Tanaka, Katsuaki; Katsube, Takayuki; Ochiai, Toshimitsu; Fukuhara, Takahiro; Kano, Takeshi; Osaki, Yukio; Izumi, Namiki; Imawari, Michio

doi:10.1111/hepr.13544

Cited by 4 publications

(9 citation statements)

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“…In the phase 1/2 study, the analysis of variance for class A, B, and C patients, including CP class as a fixed effect, was performed for the following pharmacokinetic parameters: the ln-transformed values for C max , AUC 0– τ , λ z , t 1/2, z , and CL/F. For this analysis, Child–Pugh class A and B patients were included from the open-label, phase 3b study (1338M0633) [ 14 ]. The ratios of the geometric least squares means and the corresponding 90% confidence intervals (CIs) were estimated by exponentiating the differences in means and the corresponding 90% CIs in the logarithm.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic Assessment and Treatment Effect of Lusutrombopag in Child–Pugh Class C Patients: Review of Patient Data from Two Clinical Studies and Post-Marketing Surveillance

et al. 2022

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Introduction Patients with thrombocytopenia and chronic liver disease are at increased risk of bleeding during invasive procedures due to low platelet counts. Lusutrombopag, an orally active thrombopoietin receptor agonist, increases platelet count and reduces the need for platelet transfusion in chronic liver disease patients with thrombocytopenia undergoing a planned invasive procedure. The safety of lusutrombopag in patients with Child–Pugh class C chronic liver disease is not known. The present analysis was performed to determine the pharmacokinetics, efficacy, and safety of lusutrombopag in patients with Child–Pugh class C chronic liver disease. Methods Data for patients with Child–Pugh class C chronic liver disease were collected from three data sets: a phase 1/2 Child–Pugh class C study ( n = 5) (JapicCTI-163289 [Japan Pharmaceutical Information Center]), a phase 3 pivotal study (L-PLUS 2, n = 3) (NCT02389621 [Clinicaltrials.gov]), and ongoing post-marketing surveillance ( n = 27) (JapicCTI-163432 [Japan Pharmaceutical Information Center]). Patients received lusutrombopag at 3 mg for up to 7 days. Safety and efficacy assessments were collected from two clinical studies and the post-marketing surveillance; pharmacokinetic data were collected from the phase 1/2 study. Results Mean C max and AUC 0– τ were lower in Child–Pugh class C patients than Child–Pugh class A and B; individual patients’ C max and AUC 0– τ values overlapped among Child–Pugh classes. In lusutrombopag patients who did not receive platelet transfusion ( n = 4 in phase 1/2, n = 1 in phase 3, n = 24 in post-marketing surveillance), the median (range) maximum platelet count was 88.5 × 10 9 /L (54–105 × 10 9 /L), 80 × 10 9 /L, and 91 × 10 9 /L (41–186 × 10 9 /L; n = 23), respectively. There were no treatment-related adverse events or treatment-related serious adverse events. One patient from the phase 1/2 study had a non-serious portal vein thrombosis, which was not considered treatment-related. Conclusions The analysis presented in this study suggests that lusutrombopag increases platelet counts in Child–Pugh class C patients and is safe and well tolerated in this patient population. Trial Registration L-PLUS 2: NCT02389621 (Clinicaltrials.gov). Phase 1/2: JapicCTI-163289 (Japan Pharmaceutical Information Center [JAPIC]). Post-marketing surveillance: JapicCTI-163432 (JAPIC). Supplementary Information ...

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Section: Methodsmentioning

confidence: 99%

Pharmacokinetic Assessment and Treatment Effect of Lusutrombopag in Child–Pugh Class C Patients: Review of Patient Data from Two Clinical Studies and Post-Marketing Surveillance

et al. 2022

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“…To prevent the potential risk of thrombosis due to an excessive increase in platelets after the administration of lusutrombopag, the dose-stopping rule was implemented for avoiding platelet-overshooting in the L-PLUS 1 and L-PLUS 2 studies. As an inference result of the previous studies, it is possible that there is little difference in the probability of PLT higher than 200 × 10 9 /L without the dose-stopping rule in the course of seven-day treatment of lusutrombopag, and monitoring of platelet in patients administered lusutrombopag was not necessary [26]. This study further confirmed the conclusion that the risk of platelet counts exceeding 200 × 10 9 /L with a fixed seven-day dosing regimen is low, and additional platelet monitoring is not needed during the administration of lusutrombopag.…”

Section: Discussionmentioning

confidence: 90%

Lusutrombopag for thrombocytopenia in Chinese patients with chronic liver disease undergoing invasive procedures

Ding

Zeng

et al. 2022

Hepatol Int

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Purpose Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT < 50 × 109/L) patients undergoing elective invasive procedures. Methods In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 109/L that increased to ≥ 20 × 109/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed. PLT ≥ 50 × 109/L on or after Day 8 and within 2 days before invasive procedure (alternative criteria for not requiring platelet transfusion) were also analyzed. Adverse events (AEs) were recorded. Results The proportion of responders on Day 8 was evidently higher (p = 0.0011) in the lusutrombopag group (43.2%, 19/44) versus placebo (4.5%, 1/22). And 72.7% (32/44) patients receiving lusutrombopag met the alternative criteria for not requiring platelet transfusion, while 18.2% (4/22) in the placebo group. The median maximum PLT in lusutrombopag group increased to 80.5 × 109/L, and median time to reach maximum was 14.5 days. Compared with placebo, the lusutrombopag group had a lower incidence of bleeding events (6.8% versus 13.6%), and only one patient had thrombotic-related AE. Overall, the incidence of treatment-emergent AEs was comparable between two groups. Conclusions Lusutrombopag was effective in raising PLT, diminishing platelet transfusion requirement, and documented a safety profile like the placebo in CLD and severe thrombocytopenia patients in a Chinese cohort undergoing elective invasive procedures. Chinese clinical trial registration number: CTR20192384.

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“…41 In a phase 3b study of lusutrombopag in patients with Child-Pugh class A or B CLD, patients receiving a second cycle of lusutrombopag (n = 8) had increased platelet counts similar to those of patients receiving the first cycle (n = 94). 61 In a study of lusutrombopag in 14 patients with cirrhosis, there was no significant difference in the rate of platelet count increase between the first, second, and third or later treatment cycles (p = 0.87). 62 Other studies on repeated lusutrombopag treatment in a small number of patients have reported an increase in the platelet count after the second treatment cycle that was similar to that after the first treatment cycle.…”

Section: Retreatment With Tporasmentioning

confidence: 95%

Treatment algorithm for thrombocytopenia in patients with chronic liver disease undergoing planned invasive procedures

Yoshiji

Ueno

Kurosaki

et al. 2021

Hepatology Research

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Thrombocytopenia is highly prevalent in patients with chronic liver disease (CLD) and these patients often require invasive procedures that carry a risk of bleeding. To prevent bleeding, guidelines recommend increasing platelet counts in patients with CLD who have thrombocytopenia and are planned to undergo invasive procedures. There are currently two options to increase platelet counts in patients in this setting: platelet transfusion or thrombopoietin receptor agonists (TPORAs). Several treatment algorithms have been developed in the US to help physicians choose the best course of treatment for each patient; however, to date, no such algorithm has been proposed in other countries, where the choice of treatment has been based on each physician's judgment and experience. Here, we discuss the pathogenesis and treatment of thrombocytopenia in patients with CLD, we review and present current evidence of the efficacy of TPORAs for the treatment of thrombocytopenia in patients with CLD, and we present our expert opinion on a Japanese treatment algorithm for thrombocytopenia in patients with CLD who are planned to undergo invasive procedures.

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Is platelet monitoring during 7‐day lusutrombopag treatment necessary in chronic liver disease patients with thrombocytopenia undergoing planned invasive procedures? A phase IIIb open‐label study

Cited by 4 publications

References 24 publications

Pharmacokinetic Assessment and Treatment Effect of Lusutrombopag in Child–Pugh Class C Patients: Review of Patient Data from Two Clinical Studies and Post-Marketing Surveillance

Pharmacokinetic Assessment and Treatment Effect of Lusutrombopag in Child–Pugh Class C Patients: Review of Patient Data from Two Clinical Studies and Post-Marketing Surveillance

Lusutrombopag for thrombocytopenia in Chinese patients with chronic liver disease undergoing invasive procedures

Treatment algorithm for thrombocytopenia in patients with chronic liver disease undergoing planned invasive procedures

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