Aripiprazole had significantly greater efficacy than placebo for the treatment of bipolar disorder patients in acute manic or mixed episodes and was safe and well tolerated in this randomized controlled trial.

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Background: Relamorelin, a pentapeptide ghrelin receptor agonist, accelerated gastric emptying significantly and improved symptoms in adults with diabetic gastroparesis in phase 2 trials. Aim:To assess the safety and tolerability of relamorelin across phase 2 trials. Methods: Safety assessments in patients aged 18-75 years (weight, adverse events [AEs] and laboratory tests) from two randomised, double-blind phase 2 trials (NCT01571297, NCT02357420; results published previously) were reviewed descriptively. Analysis of covariance assessed treatment effect on glycated haemoglobin (HbA1c) and blood glucose post hoc. Phase 2a and 2b trial durations were, respectively, 4 weeks (relamorelin 10 µg once or twice daily [b.d.] or placebo b.d.) and 12 weeks (relamorelin 10, 30 or 100 µg or placebo b.d.) with 1-and 2-week, singleblind placebo run-ins.Results: Among 204 phase 2a and 393 phase 2b patients, respectively, 67% and 62% were female, and 88% and 89% had type 2 diabetes. Proportions of patients reporting serious AEs were similar across treatment groups, as were those with ≥1 treatment-emergent AE (TEAE). TEAE-related discontinuations were proportionally higher in relamorelin groups than placebo. Of 12 serious TEAEs in phase 2a, none occurred in >1 patient. In phase 2b, five serious TEAEs were reported in >1 patient, and one (100 µg) died (urosepsis), all unrelated to relamorelin. In phase 2b, increased HbA1c and fasting blood glucose levels were dose-related (P < 0.0001 and P = 0.0043, respectively). Conclusions:Relamorelin showed acceptable safety and tolerability in phase 2 trials. Relamorelin may elevate blood glucose: this should be managed proactively in relamorelin-treated patients.

Summary Background Historically, measures of symptom severity of irritable bowel syndrome with constipation (IBS‐C) in clinical trials have not met the evidence requirements described in the FDA guidance on patient‐reported outcomes (PROs), which describes the evidentiary requirements and review criteria for patient‐reported outcome measures intended to support product approval or labelling claims. Aim Data from two phase 3 trials (N = 1608) of linaclotide for the treatment of IBS‐C were analysed to evaluate the psychometric properties of patient‐reported outcome measures assessing changes in the severity of abdominal and bowel symptoms. Methods A set of patient‐reported outcome assessments addressing abdominal and bowel symptoms, the IBS‐C Symptom Severity Measures, were administered daily using interactive voice response system technology. Intraclass correlation coefficients (ICCs), Pearson correlations, factor analyses, F‐tests and effect sizes were computed to evaluate the reliability, construct validity, discriminating ability and responsiveness of the IBS‐C Symptom Severity Measures in a clinical trial context. Results The IBS‐C Symptom Severity Measures showed highly satisfactory test–retest reliability (ICCs ranging from 0.79 to 0.95) and construct validity. Factor analyses indicated one factor for abdominal symptoms and another for bowel symptoms. Known‐groups F‐tests comparing subgroups based on various responder definitions were statistically significant and in the expected direction, substantiating the discriminating ability of the IBS‐C Symptom Severity Measures. Responsiveness statistics (ranging from 0.6 to 2.1) demonstrated these measures are also capable of detecting change. Conclusions The psychometric analysis results strongly support the reliability, construct validity, discriminating ability and responsiveness of the IBS‐C Symptom Severity Measures and substantiate the conclusion of linaclotide treatment benefit.

OBJECTIVES: Infliximab is indicated in Crohn's disease (CD) resistant to standard treatment (ST), but its impact on health care costs and quality-adjusted life-expectancy is incompletely understood. We assessed the cost-effectiveness of episodic (ET) and maintenance (MT) infliximab treatment in CD patients with 10-years follow-up. METHODS: A total of 212 incident adult CD patients (age at onset 34.4Ϯ14.5 years, 49.4% male) were treated with antibiotics, mesalazine, corticosteroids, thiopurines, surgery (comprising ST) over 10-years to 2004. Eight health states were defined by intensity of therapy in these patients. We determined Markov transition probabilities between these states, health care costs and QALYs in 3 month-cycles. This cohort was modeled to allow drug-refractory or pre-surgery patients to receive infliximab: either ET in one cycle, or MT in responders for a period of 1-year (MT-1yr) or for 10-years (MT-10 yrs). Transition probabilities of ST were applied to patients getting IFX; the probability of continuing infliximab in MT was set to correct for decay. Health care costs and QALYs in ET and MT were estimated for 10-years (discounted at 3%) and compared with those of ST patients. RESULTS:The average cost (QALYs gained) per patient over 10-years was €23,169 (6.7014) for ST; €21,691 (7.0403) for ET, €29,012 (7.0553) for MT-1yr, and €50,416 (7.2603) for MT-10 yrs. ST was associated with higher costs and lower outcomes and was thus dominated by ET. The incremental cost-effectiveness ratios (ICERs) of MT-1yr and MT-10 yrs over ST were €16,510/QALY gained, and €48,751/QALY gained, respectively. When compared with ET, the ICERs of MT-1yr and MT-10 yrs were €488,066/QALY gained, and €130,568/QALY gained, respectively. When the infliximab price was halved these ICERs remained very high. CONCLUSIONS: ET or MT with infliximab are either cost-saving or cost-effective when compared with ST. However, at current drug prices, MT does not provide good value for money when compared with ET. OBJECTIVES:To evaluate direct medical costs, health outcomes, and cost-effectiveness of 48-week Peginterferon alpha-2a with 2nd line 2-years Entecavir treatment versus 3 years Entecavir treatment for HBeAg-positive chronic hepatitis B according to the Response Guided Treatment (RGT) strategy in China. METHODS: A Markov model was designed to evaluate the direct medical costs and outcomes (life years and QALYs gained) of treating HBeAg-positive chronic hepatitis B in China, with a maximum analysis time horizon of 80 years. The model included 10 health states -Chronic hepatitis B (CHB), HBeAg seroconversion, HBsAg loss, CHB with resistance, Compensated cirrhosis, Decompensated cirrhosis, Hepatocellular carcinoma, Liver transplant, Post-liver transplant and death. Based on the analysis of published literature, a two-round expert panel survey was conducted among 22 hepatitis B specialists nationally to identify clinical and utility data. From the perspective of China's health insurance system, cost data was calculated based on the publ...