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Purpose To advance the implementation of consciousness-promoting therapies in patients with acute disorders of consciousness, the availability of potential therapeutic agents in formulations suitable for administration in hospitalized patients in the presence of complex comorbid conditions is paramount. The purpose of this study is to evaluate the long-term stability of extemporaneously prepared preservative-free methylphenidate hydrochloride (HCl) 5 mg/mL intravenous solution for experimental use. Methods A methylphenidate 5 mg/mL solution was prepared under proper aseptic techniques with Methylphenidate Hydrochloride, USP, powder mixed in sterile water for solution. Methylphenidate HCl 5 mg/mL solution was sterilized by filtration technique under USP –compliant conditions. Samples were stored refrigerated (2-8°C) and analyzed at approximately days 1, 30, 60, 90, 180, and 365. At each time point, chemical and physical stability were evaluated by visual inspection, pH measurement, membrane filtration procedure, turbidometric or photometric technique, and high-performance liquid chromatography analysis. Results Over the 1-year study period, the samples retained 96.76% to 102.04% of the initial methylphenidate concentration. There was no significant change in the visual appearance, pH level, or particulate matter during the study period. The sterility of samples was maintained and endotoxin levels were undetectable throughout the 1-year stability period. Conclusion Extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution was physically and chemically stable at 32, 61, 95, 186, and 365 days when stored in amber glass vials at refrigerated temperatures (2-8°C).

Background The CTOT-11 (Prevention of Cardiac Allograft Vasculopathy Using Rituximab Therapy in Cardiac Transplantation [Clinical Trials in Organ Transplantation-11]) study was a randomized, placebo-controlled, multicenter, double-blinded clinical trial in nonsensitized primary heart transplant (HTX) recipients. Objectives The study sought to determine whether B cell depletion therapy would attenuate the development of cardiac allograft vasculopathy. Methods A total of 163 HTX recipients were randomized to rituximab 1,000 mg intravenous or placebo on days 0 and 12 post-transplant. Primary outcome was change in percent atheroma volume (PAV) from baseline to 1 year measured by intravascular ultrasound. Secondary outcomes included treated episodes of acute rejection, de novo anti-HLA antibodies (including donor-specific antibodies), and phenotypic differentiation of B cells. Results There were no significant differences at study entry between the rituximab and placebo groups. Paired intravascular ultrasound measures were available at baseline and 1 year in 86 subjects (49 rituximab, 37 placebo). The mean ± SD change in PAV at 12 months was +6.8 ± 8.2% rituximab versus +1.9 ± 4.4% placebo (p = 0.0019). Mortality at 12 months was 3.4% rituximab versus 6.8% placebo (p = 0.47); there were no retransplants or post-transplant lymphoproliferative disorder. The rate of treated rejection was 24.7% rituximab versus 32.4% placebo (p = 0.28). Rituximab therapy effectively eliminated CD20+/CD19+ B cells followed by a gradual expansion of a CD19– cell population in the rituximab-treated group. Conclusions A marked, unexpected increase in coronary artery PAV with rituximab was observed during the first year in HTX recipients. One-year mortality was not impacted; however, longer-term follow-up and mechanistic explanations are required. (Prevention of Cardiac Allograft Vasculopathy Using Rituximab [Rituxan] Therapy in Cardiac Transplantation; NCT01278745)