Results of a phase I trial to assess the safety of macitentan in combination with temozolomide for the treatment of recurrent glioblastoma.

Background: There is an urgent need for additional therapies to treat recurrent glioblastoma (GBM). Preclinical studies suggest that high dose macitentan, an oral dual endothelin receptor antagonist, enhances the cytotoxic effects of temozolomide (TMZ) in GBM, improving survival. This phase I trial investigated the maximum tolerated dose of macitentan combined with TMZ in patients with recurrent GBM and assessed the safety and tolerability of high dose macitentan in these patients (NCT01499251).

Pharmacokinetics, Tolerability, and Safety of Murepavadin, a Novel Antipseudomonal Antibiotic, in Subjects with Mild, Moderate, or Severe Renal Function Impairment.

This open-label, nonrandomized, single-dose, phase 1 study evaluated the pharmacokinetics and safety of murepavadin, a novel peptide antibiotic for the treatment of serious infections. The study was conducted in 32 subjects of either sex in 4 groups (up to 8 per group) with mild (group 1), moderate (group 2), and severe (group 3) renal function impairment or with normal renal function (group 4). The degree of renal impairment of the subjects was classified at screening according to the estimated creatinine clearance (CL) according to the Cockcroft-Gault equation.

Lucerastat, an Iminosugar for Substrate Reduction Therapy: Tolerability, Pharmacodynamics, and Pharmacokinetics in Patients With Fabry Disease on Enzyme Replacement.

Lucerastat is a glucosylceramide synthase inhibitor aimed at reducing production of glycosphingolipids (GSLs), including those accumulating in Fabry disease. The safety, tolerability, pharmacodynamics, and pharmacokinetics of oral lucerastat were evaluated in an exploratory study in patients with Fabry disease. In this single-center, open-label, randomized study, 10 patients received lucerastat 1,000 mg b.

Lucerastat, an Iminosugar for Substrate Reduction Therapy: Pharmacokinetics, Tolerability, and Safety in Subjects With Mild, Moderate, and Severe Renal Function Impairment.

Lucerastat, an inhibitor of glucosylceramide synthase, has the potential for substrate reduction therapy in glycosphingolipid storage disorders such as Fabry disease. In pharmacokinetic studies in rats, dogs, and healthy subjects, the main route of elimination was renal. The pharmacokinetics, tolerability, and safety of lucerastat were evaluated in subjects with mild (group A), moderate (group B), and severe (group C) renal impairment.

Effect of Hepatic or Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Ponesimod, a Selective S1P1 Receptor Modulator.

Ponesimod, a selective S1P1 receptor modulator, is a potential therapeutic agent for autoimmune disorders. The impact of hepatic or renal impairment on the pharmacokinetics, safety and tolerability of ponesimod and its inactive metabolites, ACT-204426 and ACT-338375, was evaluated. Two separate single-centre, open-label studies with 32 (hepatic study) and 24 (renal study) male and female individuals were conducted.