A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy.

Background: This exploratory study was the first study of remimazolam in patients to assess the safety and efficacy of different single doses for procedural sedation.

Methods: Patients scheduled to undergo a diagnostic upper gastrointestinal endoscopy were randomized to receive 1 of 3 doses of remimazolam or midazolam (25 per group) in a double-blind manner. After a single dose of study drug to achieve sedation, patients underwent gastroscopy.

A phase Ib, dose-finding study of multiple doses of remimazolam (CNS 7056) in volunteers undergoing colonoscopy.

Background: We performed the first multiple dose study of remimazolam designed to assess both the feasibility of maintaining suitable sedation during colonoscopy and reversing the sedative effects of remimazolam with flumazenil.

Methods: Healthy volunteers received fentanyl followed by remimazolam for sedation during colonoscopy. Three dose groups of 15 volunteers each received remimazolam in increasing initial doses, plus top-up doses to maintain sedation for a 30-minute period.

Phase I study of Solulin, a novel recombinant soluble human thrombomodulin analogue.

Solulin is a novel recombinant soluble derivative of human thrombomodulin. In this first human study of Solulin, the safety, tolerability, pharmacokinetics and pharmacodynamics of Solulin in 30 healthy volunteers in response to single (0.6-30 mg) and 12 healthy volunteers in response to multiple (1 and 10 mg) ascending intravenous bolus doses compared to placebo are described.

Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study.

Background: Previous studies have suggested that desmoteplase, a novel plasminogen activator, has clinical benefit when given 3-9 h after the onset of the symptoms of stroke in patients with presumptive tissue at risk that is identified by magnetic resonance perfusion imaging (PI) and diffusion-weighted imaging (DWI).

Methods: In this randomised, placebo-controlled, double-blind, dose-ranging study, patients with acute ischaemic stroke and tissue at risk seen on either MRI or CT imaging were randomly assigned (1:1:1) to 90 microg/kg desmoteplase, 125 microg/kg desmoteplase, or placebo within 3-9 h after the onset of symptoms of stroke. The primary endpoint was clinical response rates at day 90, defined as a composite of improvement in National Institutes of Health stroke scale (NIHSS) score of 8 points or more or an NIHSS score of 1 point or less, a modified Rankin scale score of 0-2 points, and a Barthel index of 75-100.

Phase I trial of r viscumin (INN: aviscumine) given subcutaneously in patients with advanced cancer: a study of the European Organisation for Research and Treatment of Cancer (EORTC protocol number 13001).

Safety of aviscumine by subcutaneous route was assessed in patients with advanced cancer refractory to chemotherapy. Patients with progressive disease received escalating doses twice weekly. Treatment of the accrued 26 patients (10 colorectal cancer (CRC), 6 soft tissue sarcoma (STS), 5 melanoma (MM), 5 others) was well tolerated without substance-related grade 3 or 4 toxicities.

Binding of recombinant mistletoe lectin (aviscumine) to resected human adenocarcinoma of the lung.

Background: Lectins, carbohydrate proteins, bind to glycoconjugates of all mammalian cells, including cancer cells. Aberrant glycosylation, detected by lectin histochemistry, can predict outcome in some tumour entities. One such lectin is aviscumine (recombinant mistletoe lectin).

Adaptation and performance of an immuno-PCR assay for the quantification of Aviscumine in patient plasma samples.

An immuno-polymerase chain reaction (IPCR) assay is used to evaluate the kinetic behaviour of the novel anti-cancer drug Aviscumine in plasma samples taken from 41 patients during a 3-year clinical trial. The ultrasensitive IPCR assay employed the amplification of a detection-antibody linked marker-DNA and an internal competitor DNA for standardization, thus enabling the detection of the antigen in concentrations far below the detection limit of conventional enzyme-linked immuno-sorbent assay (ELISA). The quantification of Aviscumine was carried out using external calibration curves obtained from individual patient plasma samples, collected previous to the administration of Aviscumine, which were spiked with known amounts of the reference substance Aviscumine.