PubMed:24605793 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/24605793","sourcedb":"PubMed","sourceid":"24605793","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/24605793","text":"Perampanel for adjunctive treatment of partial-onset seizures: a pooled dose-response analysis of phase III studies.\nOBJECTIVE: To better understand the relationship between efficacy and perampanel dose, integrated actual (last) dose data from three phase III trials and an extension study (blinded Conversion Period; open-label Maintenance Period) were analyzed.\nMETHODS: Seizure frequency data were analyzed in patients who were randomized to and completed the 13-week Maintenance Period of the phase III studies on perampanel 8 mg, and who received an actual (last) dose of 12 mg during (1) the extension 16-week blinded Conversion Period or (2) weeks 1-13 of the extension Maintenance Period. Due to a treatment-by-region interaction (p = 0.042), analyses excluded patients from the Latin America region (n = 162/1,480; 10.9% of the treated cohort).\nRESULTS: Of 372 patients randomized to 8 mg in the phase III studies, 273 completed the Maintenance Period at 8 mg and 267 entered the extension study. In patients who then had an actual (last) dose of 12 mg during the extension blinded Conversion Period (n = 217), median percent change in seizure frequency per 28 days improved from -32.4% (8 mg, phase III Maintenance Period) to -44.2% (12 mg, extension blinded Conversion Period); 50% responder rates increased slightly from 37.3% to 42.9%. In patients who completed the phase III studies on 8 mg and had an actual (last) dose of 12 mg during weeks 1-13 of the extension Maintenance Period (n = 181), median percent change in seizure frequency per 28 days improved from -34.1% (phase III Maintenance Period) to -46.0% (weeks 1-13 extension Maintenance Period); 50% responder rates were 39.2% and 46.4%. Seizure control remained substantially unchanged in patients who completed the phase III studies at 12 mg and continued on that dose during the extension.\nSIGNIFICANCE: Increasing perampanel dose from 8 to 12 mg can produce additional benefits in seizure control in at least some patients who tolerate the higher dose.","tracks":[{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":291,"end":298},"obj":"HP_0000618"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"}]},{"project":"maxiaofeng52_800_3","denotations":[{"id":"T1","span":{"begin":0,"end":10},"obj":"CI"},{"id":"T2","span":{"begin":187,"end":197},"obj":"CI"},{"id":"T3","span":{"begin":518,"end":528},"obj":"CI"},{"id":"T4","span":{"begin":1891,"end":1901},"obj":"CI"},{"id":"T5","span":{"begin":53,"end":61},"obj":"DP"},{"id":"T6","span":{"begin":373,"end":380},"obj":"DP"},{"id":"T7","span":{"begin":1711,"end":1718},"obj":"DP"},{"id":"T8","span":{"begin":1958,"end":1965},"obj":"DP"},{"id":"T9","span":{"begin":1145,"end":1152},"obj":"DP"},{"id":"T10","span":{"begin":1534,"end":1541},"obj":"DP"}],"attributes":[{"subj":"T1","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T2","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T3","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T4","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T5","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T6","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T7","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T8","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T9","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T10","pred":"source","obj":"maxiaofeng52_800_3"}]},{"project":"wangzhuo19_800_3","denotations":[{"id":"T1","span":{"begin":53,"end":61},"obj":"DP"},{"id":"T2","span":{"begin":373,"end":380},"obj":"DP"},{"id":"T3","span":{"begin":1534,"end":1541},"obj":"DP"},{"id":"T4","span":{"begin":1145,"end":1152},"obj":"DP"},{"id":"T5","span":{"begin":1958,"end":1965},"obj":"DP"},{"id":"T6","span":{"begin":0,"end":10},"obj":"CI"},{"id":"T7","span":{"begin":187,"end":197},"obj":"CI"},{"id":"T8","span":{"begin":518,"end":528},"obj":"CI"},{"id":"T9","span":{"begin":1891,"end":1901},"obj":"CI"},{"id":"T10","span":{"begin":1711,"end":1718},"obj":"DP"}],"attributes":[{"subj":"T1","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T2","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T3","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T4","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T5","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T6","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T7","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T8","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T9","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T10","pred":"source","obj":"wangzhuo19_800_3"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubmedHPO","color":"#c593ec","default":true},{"id":"maxiaofeng52_800_3","color":"#93ecab"},{"id":"wangzhuo19_800_3","color":"#ec9394"}]}]}}