Background morbidity in HIV vaccine trial participants from various geographic regions as assessed by unsolicited adverse events.

BACKGROUND: Recently, more clinical trials are being conducted in Africa and Asia, therefore, background morbidity in the respective populations is of interest. Between 2000 and 2007, the International AIDS Vaccine Initiative sponsored 19 Phase 1 or 2A preventive HIV vaccine trials in the US, Europe, Sub-Saharan Africa and India, enrolling 900 healthy HIV-1 uninfected volunteers. OBJECTIVE: To assess background morbidity as reflected by unsolicited adverse events (AEs), unrelated to study vaccine, reported in clinical trials from four continents. METHODS: All but three clinical trials were double-blind, randomized, and placebo-controlled. Study procedures and data collection methods were standardized. The frequency and severity of AEs reported during the first year of the trials were analyzed. To avoid confounding by vaccine-related events, solicited reactogenicity and other AEs occurring within 28 d after any vaccination were excluded. RESULTS: In total, 2134 AEs were reported by 76% of all participants; 73% of all events were mild. The rate of AEs did not differ between placebo and vaccine recipients. Overall, the percentage of participants with any AE was higher in Africa (83%) compared with Europe (71%), US (74%) and India (65%), while the percentage of participants with AEs of moderate or greater severity was similar in all regions except India. In all regions, the most frequently reported AEs were infectious diseases, followed by gastrointestinal disorders. CONCLUSIONS: Despite some regional differences, in these healthy participants selected for low risk of HIV infection, background morbidity posed no obstacle to clinical trial conduct and interpretation. Data from controlled clinical trials of preventive interventions can offer valuable insights into the health of the eligible population.

Alginate-antacid combinations: raft formation and gastric retention studies.

BACKGROUND: Alginate-based gastroesophageal reflux disease treatments have been used extensively and fall into two main categories. Those containing alginate as the principle active agent and those containing alginate in combination with a significant amount of antacid. METHOD: The effectiveness of the raft formed by a new alginate/antacid suspension (Gaviscon Double Action Liquid, GDAL), in which calcium carbonate was the main antacid ingredient, was compared with those of existing alginate/antacid suspensions. RESULT: GDAL had similar raft strength and improved raft resilience than Gaviscon Liquid (GL), and both were significantly greater than five other products tested. Gastric retention of GDAL was similar to that of GL. CONCLUSION: the in vitro and in vivo performance is maintained in the new GDAL formulation even with higher antacid levels and the product is as good as, or better than, previous formulations.

The combined use of ibutilide as an active control with intensive electrocardiographic sampling and signal averaging as a sensitive method to assess the effects of tadalafil on the human QT interval.

OBJECTIVES: This study was designed to evaluate effects of tadalafil, a phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction (ED), on the QT interval. BACKGROUND: Cardiovascular disease is common in men with ED. Men with cardiovascular disease and ED may have decreased cardiac repolarization reserve. METHODS: Effects of tadalafil (100 mg by mouth), ibutilide (0.002 mg/kg intravenously), and placebo on the QT interval in healthy men were compared (placebo and tadalafil [n = 90], with a subset [n = 61] receiving all treatments; mean age 30 years, range 18 to 53 years). Electrocardiographic sampling was done for two days before treatment and on treatment days. The QT was corrected for RR interval with five correction methods, including an individual correction (QTcI). Plasma concentrations of tadalafil were measured to evaluate concentration-QT effect relationships. RESULTS: At the time corresponding to maximum plasma concentration of tadalafil, the mean difference in the change in QTcI between tadalafil and placebo was 2.8 ms; tadalafil was equivalent to placebo (a priori, upper limit of 90% confidence interval < 10 ms [actual = 4.4 ms]; post hoc, upper limit of 95% confidence interval < 5 ms [actual = 4.8]). The active control, ibutilide, significantly increased QTcI by 6.9 and 8.9 ms compared with tadalafil and placebo, respectively. Similar statistical results were obtained with four additional QT correction methods. No subject had a QTcI > or = 450 ms or an increase in QTcI > or = 30 ms with any treatment. CONCLUSIONS: Based on the a priori statistical test of equivalence, placebo and high-dose tadalafil produced equivalent effects on the QT interval. This study reliably discerned 5- to 10-ms changes in corrected QT in the ibutilide active control group.

Tolerance of ocular iontophoresis in healthy volunteers.

To evaluate ocular tolerance, healthy volunteers were iontophoresed transclerally using novel OcuPhor trade mark hydrogel drug delivery applicators filled with balanced salt solution. In this three-period crossover study in 24 male and female subjects, 16 subjects received 0 mA and two of the following DC currents: 0.1, 0.5., 1.0, 2.0, 3.0, or 4.0 mA for 20 min; 6 subjects received 3 mA for 20 min and 1.5 mA for 40 min (both equivalent to 60 mAmin total charge). Safety and tolerance were determined by subjective VAS and objective ophthalmic assessments. Subjects were evaluated before and up to 22 hr after dosing. The applicators were well-tolerated and no clinically significant changes in symptomology or in ophthalmic assessments were seen following exposure to 0-3.0 mA for 20 min or 1.5 mA for 40 min. At 4.0 mA 2 of 4 subjects reported a burning sensation under the applicator during dosing which resolved by 22 hr post-dose; superficial changes in fluorescein staining were observed at 1 hr, but not at 22 hr. The OcuPhor trade mark system has promise for noninvasive drug delivery to the eye.