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Objective. The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo- controlled study. These data were also pooled with those from two similar phase 3 studies to explore the effects of methadone on treatment response. Methods. In the primary study, adults with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were randomized to receive lubiprostone 24mcg or placebo twice daily for 12weeks. The primary end point was a change from baseline in the frequency of SBMs at week 8 in patients without a prior dose reduction. For the pooled analysis, the efficacy of lubiprostone was compared with placebo in patients receiving methadone or nonmethadone opioids. Responders were defined as patients with nine or more weeks of nonmissing SBM data who had one or more additional SBMs per week from baseline for each week that data were available and three or more SBMs per week for nine or more weeks. Results. In the primary study, the change from baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo groups (P50.842). In the pooled analysis, the response rate was significantly higher with lubiprostone treatment vs placebo for patients receiving nonmethadone opioids (P=0.002) but was similar between lubiprostone treatment and placebo in patients receiving methadone (P=0.692). The safety profile of lubiprostone was unaffected by methadone use. Conclusions. The phase 3 study did not meet its primary efficacy end point. However, analysis of pooled data from all phase 3 studies in the OIC clinical development program, stratified by methadone opioid usage, confirmed that lubiprostone is effective for treatment of OIC in patients taking nonmethadone opioids; no safety concerns were identified based on the type of opioid used. [ABSTRACT FROM AUTHOR]

Objective To determine the efficacy, tolerability, and safety of ascending doses of Adhesive Dermally-Applied Microarray (ADAM) zolmitriptan versus placebo for acute migraine treatment. Background ADAM is a novel patient-administered system for intracutaneous drug administration. In a phase 1 pharmacokinetic study, zolmitriptan administered using ADAM had much faster absorption than oral administration with higher exposure in the first two hours. Methods This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 2b/3 study evaluating ADAM zolmitriptan 1 mg, 1.9 mg, and 3.8 mg versus placebo. Co-primary endpoints were pain freedom and freedom from most bothersome other migraine-associated symptom 2 hours post-dose. Results Of patients treated with ADAM zolmitriptan 3.8 mg or placebo, 41.5% and 14.2%, respectively were pain-free 2 hours post-dose ( p = 0.0001) and 68.3% and 42.9% were free from their most bothersome other symptom ( p = 0.0009). Due to the fixed sequential testing methodology, formal statistical significance was not established for secondary endpoints. However, the proportion of patients who were photophobia-free, phonophobia-free, and nausea-free at 2 hours post-dose was higher in the ADAM zolmitriptan 3.8 mg group compared with placebo, as were the percentages of patients who were pain-free, and who experienced pain relief up to 48 hours post-dose. Systemic adverse events were consistent with previous triptan trials, and included dizziness, paresthesia, muscle tightness, and nausea, all of which occurred in < 5% of patients in any group. Application site reactions were generally mild and resolved within 48 hours, although erythema and bruising persisted for longer periods in some patients. Conclusion ADAM zolmitriptan 3.8 mg provides effective relief of migraine headache and associated most bothersome symptoms compared with placebo, and is well-tolerated. ClinicalTrials.gov NCT02745392. [ABSTRACT FROM AUTHOR]