Monthly oral ibandronate is well tolerated and efficacious in postmenopausal women: Results from the monthly oral pilot study

Context: Ibandronate, a potent, nitrogen-containing bisphosphonate developed for intermittent administration in postmenopausal osteoporosis, aims to overcome current adherence issues with daily and weekly oral bisphosphonates through once-monthly oral dosing. Objective: The purpose of this study was to investigate the safety, pharmacodynamics, and pharmacokinetics of once-monthly oral ibandronate. Design: A randomized, 3-month, double-blind, placebo-controlled, phase I study (Monthly Oral Pilot Study) was conducted. Setting: The study was conducted at five clinical trial centers in the United Kingdom and Belgium. Patients or Other Participants: Subjects were postmenopausal women (age, 55 - 80 yr; >= 3 yr post menopause; n = 144). Intervention(s): Once-monthly oral ibandronate 50, 100, or 150 mg or placebo was used. After the first cycle, the 50-mg arm was split, with participants continuing on either 50 or 100 mg. Main Outcome Measure(s): Primary outcome measures were safety, serum and urinary C-telopeptide (CTX), and serum ibandronate AUC(0-infinity). Results: Once- monthly oral ibandronate was well tolerated, with a similar overall and upper gastrointestinal safety profile to placebo. Once- monthly ibandronate was also highly effective in decreasing bone turnover; substantial reductions from baseline in serum CTX (-56.7% and -40.7% in the 150- and 100- mg arms, respectively; P < 0.001 vs. placebo) and urinary CTX (-54.1% and -34.6%, respectively; P < 0.001 vs. placebo) were observed at d 91 (30 d after the final dose). Analysis of the area under the effect curve (d1 - 91) for change from baseline (percent x days) in serum CTX and urinary CTX indicated a dose- response relationship. The AUC(0-infinity) for ibandronate increased with dose but not in a dose- proportional manner. Conclusions: These findings indicate a potential role for once-monthly oral ibandronate in the treatment of postmenopausal osteoporosis

ADHERE: randomized controlled trial comparing renal function in de novo kidney transplant recipients receiving prolonged-release tacrolimus plus mycophenolate mofetil or sirolimus

ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 postkidney transplant, in patients who received prolongedrelease tacrolimus-based immunosuppressive regimens. On Days 0?27, patients received prolonged-release tacrolimus (initially 0.2 mg/kg/day), corticosteroids, and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolongedrelease tacrolimus (?25% dose reduction on Day 42) plus sirolimus (Arm 2). The primary endpoint was glomerular filtration rate by iohexol clearance (mGFR) at Week 52. Secondary endpoints included eGFR, creatinine clearance (CrCl), efficacy failure (patient withdrawal or graft loss), and patient/graft survival. Tolerability was analyzed. The full-analysis set comprised 569 patients (Arm 1: 287; Arm 2: 282). Week 52 mean mGFR was similar in Arm 1 versus Arm 2 (40.73 vs. 41.75 ml/min/1.73 m2; P = 0.405), as were the secondary endpoints, except composite efficacy failure, which was higher in Arm 2 versus 1 (18.2% vs. 11.5%; P = 0.002) owing to a higher postrandomization withdrawal rate due to adverse events (AEs) (14.4% vs. 5.2%). Results from this study show comparable renal function between arms at Week 52, with fewer AEs leading to study discontinuation with prolonged-release tacrolimus plus MMF (Arm 1) versus lower dose prolonged-release tacrolimus plus sirolimus (Arm 2)

A new therapeutic protocole for the prevention of caustic esophageal stenosis : The advantage of a silastic calibrating probe

L'amélioration du pronostic fonctionnel des brûlures caustiques digestives est liée à la prévention des sténoses œsophagiennes. 139 patients sont examinés entre janvier 1979 et février 1981 au Centre d'Endoscopie Digestive de l'Hôpital Edouard-Herriot (Lyon) dans les 24 à 48 heures après absorption volontaire ou accidentelle d'un produit caustique. Le protocole thérapeutique consiste en une nutrition parentérale exclusive avec mise en place précoce, en collaboration avec les otorhinolaryngologistes, d'une sonde de calibrage en silastic pour la prévention des sténoses oesophagiennes chez les patients porteurs d'un stade 2 circulaire et d'un stade 3 oesophagien. Les auteurs insistent sur l'intérêt du calibrage oesophagien pour la prévention des sténoses des stades 2 circulaires. 18% seulement de sténose dans cette série contre 82 % dans une série précédemment publiée ne comportant pas de calibrage oesophagien. Aucun accident ou incident imputable à la sonde n'est observé; la tolérance, facilitée par la mise en place de la sonde sous anesthésie générale, est bonne chez les patients. Par contre l'intérêt du calibrage oesophagien pour les stades 3 n'est pas probant dans cette série. Le nombre trop restreint de malades porteurs de lésions de ce stade empêche cependant toute conclusion définitive