Buccal mucosal irritation studies of sublingual apomorphine film (APL-130277) in Syrian golden hamsters.

AIM: Determine the potential for cheek pouch buccal mucosa irritation in hamsters following administration of apomorphine hydrochloride film (APL-130277). METHODS: Three studies were conducted with Syrian golden hamsters. (First study, four hamsters received APL-130277 three times a day [TID] for 7 days. Second study, four hamsters received APL-130277 once a day [QD] for days 1-3, twice a day [BID] for days 4-7 and TID for days 8-21. Third study, 32 hamsters received either a placebo strip or APL-130277-dosed TID for 28 days). For all the studies, the macroscopic appearance of the buccal cavities was evaluated throughout the study. In the third study, all animals were necropsied on day 29, and macroscopic and histopathological examinations were performed. RESULTS: In the first and second studies, the buccal mucosa of the cheek pouch did not show any signs of irritation. In the third study, administration of APL-130277-dosed TID for 28 consecutive days did not result in observable local irritation of the buccal mucosa. CONCLUSION: In all the studies, APL-130277 produced no irritation of the cheek pouch buccal mucosa.

Improvement in nasolabial folds with a hyaluronic acid filler using a cohesive polydensified matrix technology: results from an 18-month open-label extension trial.

BACKGROUND: Repeat treatments of nonpermanent dermal fillers are used in the long-term treatment of wrinkles and folds and to volumize. OBJECTIVE To determine the safety and effectiveness of a nonanimal-sourced hyaluronic acid (HA) (which uses a cohesive polydensified matrix (CPM) technology [CPMHA]) for the treatment of nasolabial folds (NLFs) during an 18-month open-label extension trial. METHODS AND MATERIALS: Ninety-five of 118 subjects continued with this optional open-label extension of a split-face, double-blind trial. All subjects received CPMHA in both NLFs at 24 weeks after treatment in this study and were assessed at weeks 32, 48, 72, and 96. Touch-ups were allowed for optimal correction. Safety was assessed according to reported adverse events (AEs) and serum antibody measurement. RESULTS: At all four post-week 24 time points, the severity of the NLFs showed a decrease from baseline on the Wrinkle Severity Rating Scale. The effects persisted in the majority (∼80%) of subjects without repeat treatment for at least one interval of 48 weeks. The study filler was well tolerated, with only one related AE (injection site bruising) reported. Little potential for immunogenic reactions was identified. CONCLUSION: This CPMHA is a well-tolerated and effective treatment for at least 48 weeks in the majority of subjects for the correction of moderate to severe NLFs with repeat injections given over an 18-month period.

Evaluation of an onion extract, Centella asiatica, and hyaluronic acid cream in the appearance of striae rubra.

This study evaluated the effect of an onion extract cream with Centella asiatica and hyaluronic acid in improving the appearance of striae rubra (SR). Women participants with bilateral, outer aspect of the thigh SR were randomized to apply a quarter-sized amount of the onion extract cream twice daily for 12 weeks to the randomized left or right, outer aspect of the thigh. No treatment was administered to the contralateral side. Participants were evaluated at weeks 2, 4, 8, and 12. Primary efficacy endpoints included color, texture, softness, and overall appearance of SR by the participant and investigator at week 12. The treated thigh demonstrated a statistically significant difference in the mean change in participant and investigator evaluations in overall appearance, texture, color, and softness compared with the untreated thigh at week 12. No adverse events occurred during the study. The onion extract cream was well tolerated and significantly improved the appearance of SR in women.

Double-blind, randomized comparison of olanzapine versus fluphenazine in the long-term treatment of schizophrenia.

This study was undertaken to evaluate the efficacy and safety of olanzapine compared with fluphenazine in the treatment of patients who met the Diagnostic and Statistical Manual, fourth edition (DSM-IV) diagnostic criteria for schizophrenia or schizoaffective disorder. This was a long-term (22-week), randomized, double-blind, parallel clinical trial. Sixty patients (mean age, 35.4 years) were randomly assigned to either olanzapine (n=30) or fluphenazine (n=30). They received treatment at three centers in Croatia during a 22-week study period and were assessed weekly for the first 6 weeks and monthly thereafter. Efficacy was measured using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Rating Scale (PANSS) and the Clinical Global Impression (CGI) Severity and Improvement scores. The Hillside Akathisia Scale (HAS), Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), vital signs, laboratory tests, and treatment-emergent adverse events were assessed to evaluate safety. The olanzapine group showed significantly greater mean decreases from baseline to endpoint for BPRS total (-25.8 vs. -16.5, P=.035), PANSS total (-45.7 vs. -29.5, P=.037), PANSS positive (-13.0 vs. -7.9, P=.034), and CGI Severity (-2.2 vs. -1.3, P=.031) scores. The olanzapine group showed greater mean decreases on all measures of extrapyramidal symptoms, significantly so for the SAS (-2.1 vs. 1.9, P=.004) and HAS (-3.4 vs. 2.6, P=.028). Patients in the fluphenazine group experienced a higher incidence of treatment-emergent adverse events (76.7% vs. 50.0%, P=.032). Weight gain was the most frequently reported adverse event in the olanzapine group (16.7% vs. 0.0%, P=.020). Akathisia (30.0% vs. 10.0%, P=.053) and insomnia (20.0% vs. 0.0%, P=.010) appeared most frequent in the fluphenazine group. Daily use of anticholinergics and benzodiazepines were both significantly greater for the fluphenazine group (P=.003 and.04, respectively). No significant changes were observed in vital signs, ECG, or clinical chemistry. The study indicates that olanzapine has advantages in both efficacy and safety compared to fluphenazine; however, the small sample size limits our ability to draw definitive conclusions.