A 24-Week Anemia Correction Study of Daprodustat in Japanese Dialysis Patients.

Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia of chronic kidney disease. This 24-week, phase 3, open-label study (NCT02829320) evaluated whether daprodustat could achieve and maintain target hemoglobin levels in Japanese hemodialysis patients with anemia not receiving an erythropoiesis-stimulating agent. Twenty-eight patients received daprodustat 4 mg once daily for 4 weeks, after which doses were adjusted to achieve a hemoglobin target of 10.0 to 12.0 g/dL (inclusive). Baseline mean hemoglobin was 9.10 g/dL and mean change from baseline at 4 weeks was 0.79 g/dL (95% CI, 0.53 to 1.05). Mean hemoglobin levels reached the target range by week 8 and were maintained within this range through week 24. Daprodustat 4 mg once daily increased hemoglobin over the first 4 weeks. Throughout the 24-week study, daprodustat achieved and maintained hemoglobin within the target range and no new safety concerns were identified in hemodialysis patients not receiving erythropoiesis-stimulating agents.

A phase I/Ib study of trametinib (GSK1120212) alone and in combination with gemcitabine in Japanese patients with advanced solid tumors.

BACKGROUND: Trametinib is an inhibitor of MEK1/MEK2 activation and kinase activity. In order to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of single-agent trametinib (part 1) and trametinib in combination with gemcitabine (part 2), we undertook the first clinical study of this combination in Japanese patients with cancer and herein report our results. METHODS: In part 1, 13 patients with advanced solid tumors were enrolled into 3 dose cohorts, receiving trametinib once daily at a dose of 1.0, 2.0, or 3.0 mg. In part 2, 5 patients with pancreatic cancer received trametinib (2.0 mg once daily) in combination with gemcitabine (1000 mg/m(2)). RESULTS: In part 1, a dose-limiting toxicity was observed in a patient in the 2.0-mg dose cohort, but the maximum tolerated dose was not reached at doses up to 3.0 mg daily. The best overall response was a PR in 1 patient, and 6 patients had SD. In part 2, the combination of trametinib and gemcitabine was tolerated for a short period of time. However, serious interstitial lung disease (ILD) was observed in 3 of 5 patients 4 weeks or more after the start of the treatment, including 1 fatal case. Three patients achieved a PR, and 2 patients had SD. The most common adverse event was rash (85 % in part 1 and 100 % in part 2). CONCLUSIONS: Trametinib monotherapy was tolerable in Japanese patients with cancer. However, the combination of trametinib plus gemcitabine carried a higher risk as compared with monotherapy, during which no ILD was observed. (ClinicalTrials.gov number, NCT01324258.).