Novel Parathyroid Hormone-Based Bone Graft, KUR-113, in Treatment of Acute Open Tibial Shaft Fracture: A Phase-2 Randomized Controlled Trial.

Background: Treatment of an open tibial shaft fracture (TSF) is complex, and many cases are associated with delayed bone union or malunion. Parathyroid hormone (PTH) plays a key role in bone metabolism. A peptide fragment of PTH (PTH1-34) has been shown to promote bone healing.

First Clinical Experience with ONO-4232: A Randomized, Double-blind, Placebo-controlled Healthy Volunteer Study of a Novel Lusitropic Agent for Acutely Decompensated Heart Failure.

Purpose: The aim of this study was to evaluate the safety, tolerability, and pharmacokinetic parameters of up to 15 dose levels of ONO-4232, a selective agonist for the EP4 subtype of the prostaglandin E2 receptor, with a dual left ventricular lusitropic and venodilatory action, in healthy, adult, male and female volunteers.

Methods: In this randomized, single-center, double-blind, placebo-controlled, single-dose, sequential-group escalation, first in human study, ONO-4232 (0.001, 0.

A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies.

We report the results of a multicenter phase 1 dose-escalation study of the selective Bruton tyrosine kinase (BTK) inhibitor ONO/GS-4059 in 90 patients with relapsed/refractory B-cell malignancies. There were 9 dose-escalation cohorts ranging from 20 mg to 600 mg once daily with twice-daily regimens of 240 mg and 300 mg. Twenty-four of 25 evaluable chronic lymphocytic leukemia (CLL) patients (96%) responded to ONO/GS-4059, with a median treatment duration of 80 weeks; 21 CLL patients remain on treatment.

Mechanical stability in a human radius fracture treated with a novel tissue-engineered bone substitute: a non-invasive, longitudinal assessment using high-resolution pQCT in combination with finite element analysis.

The clinical gold standard in orthopaedics for treating fractures with large bone defects is still the use of autologous, cancellous bone autografts. While this material provides a strong healing response, the use of autografts is often associated with additional morbidity. Therefore, there is a demand for off-the-shelf biomaterials that perform similar to autografts.

Adjustment of carbamazepine dose to offset the effects of the interaction with remacemide hydrochloride in a double-blind, multicentre, add-on drug trial (CR2237) in refractory epilepsy.

Purpose: The efficacy of remacemide hydrochloride (REM) as an antiepileptic drug (AED) was tested in a double-blind, add-on trial in patients with refractory epilepsy. Concurrent drugs included carbamazepine (CBZ). The interfering effects of the pharmacokinetic interaction between REM and CBZ were offset by the monitoring of plasma CBZ concentration and the appropriate reduction of CBZ dose by an unblinded observer.

Lack of pharmacokinetic interaction between remacemide hydrochloride and sodium valproate in epileptic patients.

A randomized, double-blind, placebo-controlled cross-over study of adjuvant treatment with remacemide hydrochloride was carried out in 17 patients taking sodium valproate (VPA) as monotherapy. Plasma concentration profiles of VPA, remacemide, and its active desglycinyl metabolite (ARL12495XX) were determined following single (300 mg) and multiple dosing (150 or 300 mg twice daily) of remacemide hydrochloride for 14 days with a 300-mg final dose. Central nervous system side-effects were more common at the higher dose, which prompted dosage reduction to 150 mg twice daily for subsequent patients partway through the study.

Mutual interaction between remacemide hydrochloride and phenytoin.

A randomised, double-blind, placebo-controlled crossover study of add-on remacemide hydrochloride was carried out in epilepsy patients being treated with phenytoin (PHT) monotherapy. Eleven patients were recruited, ten of whom completed the study. Plasma concentration profiles of PHT, remacemide, and its active desglycinyl metabolite (ARL12495XX) were determined following single and multiple dosing with remacemide hydrochloride.

Mutual interaction between remacemide hydrochloride and carbamazepine: two drugs with active metabolites.

Purpose: We wished to determine mutual interaction of two drugs with active metabolism: remacemide, hydrochloride and carbamazepine (CBZ).

Methods: A randomized, double-blind, placebo-controlled cross-over study of add-on remacemide hydrochloride was performed in 10 of 14 recruited patients being treated with CBZ monotherapy. Forty-eight-hour concentration profiles of CBZ, its active epoxide metabolite (CBZ-E), remacemide, and its desglycinyl metabolite (ARL12495XX) were assayed after single and multiple dosing.

Clinical evaluation of 1% cyclosporine for topical treatment of keratoconjunctivitis sicca in dogs.

Keratoconjunctivitis sicca (KCS) is a prevalent and often vision-threatening condition in dogs. In several reports, 2% cyclosporine (cyclosporin A, CsA) was described as effective in modulating the clinical signs of KCS. This study was designed to compare the efficacy of 1% CsA vs a placebo, using a randomized double-blind clinical trial.

Acute blindness associated with intracranial tumors in dogs and cats: eight cases (1984-1989).

Rostral and middle cranial fossa tumors affecting the optic chiasm and resulting in acute visual deficits were diagnosed in 7 dogs and 1 cat. Blindness and dilated nonresponsive pupils were the primary signs in all animals. Other concurrent neurologic deficits were either absent or were equivocal.

A multicentre study of tenoxicam for the treatment of osteo-arthritis and rheumatoid arthritis in general practice.

A study was undertaken to investigate the efficacy and tolerability of 20 mg/day tenoxicam given orally for 12 weeks in a general practice setting in a broad range of patients suffering from osteo-arthritis or rheumatoid arthritis. The group of 2963 patients was recruited from 252 general practices. Some patients (60%) continued treatment into the long-term phase of the trial, beyond 12 weeks, whereas other patients (31%) elected to continue treatment beyond 52 weeks.

Treatment of glaucoma by use of transscleral neodymium:yttrium aluminum garnet laser cyclocoagulation in dogs.

Neodymium:yttrium aluminum garnet (Nd:YAG) laser energy was transsclerally applied to the ciliary body of 56 eyes of 37 dogs for treatment of glaucoma. Forty-four eyes were glucomatous at the time of treatment, and 12 normotensive eyes with ciliary cleft closure were treated prophylactically. Glaucoma was primary in 35 dogs and secondary in 2 dogs (1 eye in each dog).

A large multicentre, parallel group, double-blind study comparing tenoxicam and piroxicam in the treatment of osteoarthritis and rheumatoid arthritis.

A total of 1,328 patients with osteoarthritis or rheumatoid arthritis were entered into this double-blind, parallel group study of tenoxicam and piroxicam. The patient populations were well matched. An improvement was seen in pain on moving and at night in both groups and in both indications.

Spinal analgesia using bupivacaine 0.5% plain. Variation in the extent of the block with patient age.

Bupivacaine 0.5% plain solution was used to produce spinal analgesia on 63 occasions. In 33 patients a fixed dose of 4 ml injected at the L2/3 interspace at 0.