Publications (12)95.76 Total impact
-
Article: Total migraine freedom, a potential primary endpoint to assess acute treatment in migraine: comparison to the current FDA requirement using the complete rizatriptan study database.
[show abstract] [hide abstract]
ABSTRACT: To examine total migraine freedom (TMF), defined as pain freedom and absence of associated symptoms, using rizatriptan clinical trial data and to explore advantages of TMF as a single primary composite efficacy endpoint. The FDA has set a higher regulatory hurdle for registration of new migraine agents requiring both pain freedom (or relief) and absence of each associated symptom (phonophobia, photophobia, and nausea). Twelve studies representing phase III + efficacy/safety studies of rizatriptan 10 mg in adults treating migraine were included in the meta-analysis. The percentage of patients achieving TMF at 2 hours by study and combined by treatment group was summarized by treatment paradigm (early/mild pain, moderate/severe, menstrual migraine). To demonstrate the impact of the strict migraine regulatory hurdle on clinical trial design and to compare it to TMF, simulation via bootstrap sampling was used. Odds ratios (rizatriptan vs placebo, all P < .001) for TMF were 6.2 (95% CI: [4.9, 7.7]) for moderate/severe, 2.7 (95% CI: [1.8, 4.0]) for menstrual, and 3.1 (95% CI: [2.4, 4.0]) for early/mild. Most with moderate/severe migraine reported photophobia and/or phonophobia at baseline, but only half had nausea. Simulation results showed a substantial loss of power analyzing absence of pain and each symptom compared with the composite TMF endpoint across all treatment paradigms. Rizatriptan 10 mg was superior to placebo in achieving TMF at 2 hours post-dose across all treatment paradigms. Given that the majority of patients with migraine do not exhibit all 3 associated symptoms, the TMF endpoint has significant advantages vs establishing efficacy on pain and each symptom individually.Headache The Journal of Head and Face Pain 10/2010; 51(3):356-68. · 2.52 Impact Factor -
Article: Rizatriptan 10-mg ODT for early treatment of migraine and impact of migraine education on treatment response.
[show abstract] [hide abstract]
ABSTRACT: To examine the efficacy of rizatriptan 10-mg orally disintegrating tablet (ODT) for treating migraines of mild intensity soon after onset, with or without patient-specific migraine education. Studies have shown rizatriptan tablet efficacy in early migraine treatment. In this randomized, placebo-controlled, double-blind, factorial design study, adults with a history of migraine were assigned to rizatriptan 10-mg ODT patient education (personalized summary of early migraine signs and symptoms) or placebo patient education in a 1 : 1 : 1 : 1 ratio. Patients were instructed to treat 1 attack at the earliest time they knew that their headache was a migraine, while pain was mild. During the next 24 hours, patients assessed pain severity, associated symptoms, functional disability, use of rescue medication, and treatment satisfaction. The primary endpoint was pain freedom at 2 hours; a key secondary endpoint was 24-hour sustained pain freedom. Of 207 patients randomized to treatment, 188 (91%) treated a study migraine. Significantly more patients taking rizatriptan reported pain freedom at 2 hours compared with placebo (66.3% vs 28.1%, P < .001). Similarly, significantly more patients taking rizatriptan reported 24-hour sustained pain freedom (52.2% vs 17.7%, P < .001). A greater proportion of patients in the rizatriptan + education group reported pain freedom at 2 hours compared with those in the rizatriptan + no education group (71.7% vs 60.9%, P = .430). Few adverse events were reported. Rizatriptan 10-mg ODT, when taken early, while headache pain is mild, was superior to placebo at providing pain freedom at 2 hours and 24-hour sustained pain freedom.Headache The Journal of Head and Face Pain 06/2009; 49(5):687-96. · 2.52 Impact Factor -
Article: Rizatriptan efficacy in ICHD-II pure menstrual migraine and menstrually related migraine.
[show abstract] [hide abstract]
ABSTRACT: To examine the efficacy of rizatriptan for the treatment of pure menstrual migraine (PMM). In 2004, the International Headache Society proposed new research criteria for menstrual migraine (International Classification of Headache Disorders [ICHD-II]). Two subtypes were defined: PMM, in which attacks occur exclusively with menstruation, and menstrually related migraine (MRM), in which attacks may also occur at other times of the cycle. The 2 protocols (MM1 and MM2) were identical randomized, double-blind studies. Adult patients with ICHD-II menstrual migraine were assigned to either rizatriptan 10-mg tablet or placebo (2:1). Patients were to treat a single menstrual migraine attack of moderate or severe pain intensity. This prospectively planned substudy pooled data from patients with a diagnosis of PMM from both studies. The primary substudy endpoint was 2-hour pain relief. Efficacy data were summarized for patients with a diagnosis of MRM. Of 707 (MM1: 357, MM2: 350) patients treated in the study, 146 patients (MM1: 81, MM2: 65) had a diagnosis of PMM. The percentage of patients reporting 2-hour pain relief was significantly greater for rizatriptan than for placebo for both PMM (73% vs 50%, P = .006) and MRM subgroups (71% vs 52%, P < .001). Most other efficacy endpoints favored rizatriptan compared with placebo in patients with either PMM or MRM. Rizatriptan 10 mg was superior to placebo for the treatment of PMM, as measured by 2-hour pain relief. Rizatriptan was also effective for the treatment of MRM and for relief of migraine-associated symptoms for both headache subtypes.Headache The Journal of Head and Face Pain 04/2008; 48(8):1194-201. · 2.52 Impact Factor -
Article: Elimination of migraine-associated nausea in patients treated with rizatriptan orally disintegrating tablet (ODT): a randomized, double-blind, placebo-controlled study.
[show abstract] [hide abstract]
ABSTRACT: To confirm the efficacy of rizatriptan 10 mg orally disintegrating tablet (ODT) for the elimination of migraine-associated nausea. Pooled studies of rizatriptan analyzing elimination of nausea as a secondary endpoint showed that 65% of rizatriptan patients reported elimination of nausea at 2 hours compared with 41% of patients taking placebo. This was a multicenter, randomized, double-blind, placebo-controlled single-attack trial enrolling adult patients with at least a 6-month history of migraine who typically experience migraine-associated nausea. Patients treated a moderate or severe migraine headache at the earliest sign of nausea with either rizatriptan 10 mg ODT or placebo (2 : 1). The primary endpoint was elimination of nausea at 2 hours postdose, and the secondary endpoint was pain relief at 2 hours postdose. Although not statistically significant, a greater percentage of patients had elimination of nausea at 2 hours with rizatriptan compared with placebo (70.3% vs 62.0%, P = .165, odds ratio [95% CI] = 1.45 [0.86, 2.46]). When patients were grouped by baseline headache severity, rizatriptan showed a greater advantage than placebo for patients with moderate pain (rizatriptan 72.8% vs placebo 57.4%), but no difference for patients with severe pain (rizatriptan 67.7% vs placebo 66.7%). There were significantly more patients who achieved 2-hour pain relief with rizatriptan (69.7% vs 54.3%, P = .012, odds ratio [95% CI] = 1.94 [1.16, 3.25]). Although the efficacy of rizatriptan 10 mg ODT for the elimination of migraine-associated nausea was comparable to that seen in previous rizatriptan trials, the higher-than-usual placebo response prevented a finding of a statistically significant difference. There was a sizable difference in placebo response between patients who treated moderate vs severe migraine. Rizatriptan was effective for 2-hour pain relief.Headache The Journal of Head and Face Pain 04/2008; 48(3):368-77. · 2.52 Impact Factor -
Article: Efficacy of rizatriptan for menstrual migraine in an early intervention model: a prospective subgroup analysis of the rizatriptan TAME (Treat A Migraine Early) studies.
[show abstract] [hide abstract]
ABSTRACT: A prospective subgroup analysis of the TAME (Treat A Migraine Early) studies examined the efficacy of rizatriptan in patients treating a menstrual migraine attack. Both TAME studies were randomized, placebo-controlled, and double-blind. Adults with migraine were assigned (2:1) to either rizatriptan 10-mg tablet or placebo. Patients were instructed to treat within 1 hour of migraine onset and when the pain was mild. The primary endpoint was 2-hour pain freedom. The diagnosis of menstrual migraine was established according to the revised 2004 International Headache Society (IHS) diagnostic criteria. Data from both studies were pooled for logistic regression analyses. A test for interaction was performed to compare rates of 2-hour pain freedom between patients treating a menstrual and non-menstrual attack. A total of 94 patients (63 in the rizatriptan group and 31 in the placebo group) met IHS criteria for menstrual migraine and treated a menstrual attack. The percentage of patients reporting 2-hour pain freedom was significantly greater for rizatriptan than for placebo (63.5% vs 29.0%; odds ratio = 4.5; 95% confidence interval: 1.7, 11.9; P = .002) in those treating a menstrual attack. In those treating with rizatriptan, the percentage of patients with 2-hour pain freedom did not statistically differ between those treating a menstrual or non-menstrual migraine attack (63.5% vs 57.5%; P = .454). Rizatriptan 10 mg was effective for the treatment of menstrual migraine in an early intervention model, as measured by 2-hour pain freedom. Rates of 2-hour pain freedom were comparable for patients treating menstrual and non-menstrual migraine attacks with rizatriptan.Headache The Journal of Head and Face Pain 03/2008; 48(2):226-35. · 2.52 Impact Factor -
Article: Comment on eletriptan in migraine patients reporting unsatisfactory response to rizatriptan.
Headache The Journal of Head and Face Pain 04/2007; 47(3):452; author reply 452-3. · 2.52 Impact Factor -
Article: Efficacy of Rizatriptan 10 mg administered early in a migraine attack.
[show abstract] [hide abstract]
ABSTRACT: To determine if administration of rizatriptan 10 mg is superior to placebo for the early treatment of acute migraine, while the pain is mild. Past studies have suggested that treatment outcomes can be improved if a triptan is administered early in the time course of a migraine attack. Two randomized, parallel, placebo-controlled, double-blind studies. TAME (Treat A Migraine Early)1 was conducted at 46 centers in the United States; TAME2, at 48 centers in the United States. Totally, 1030 adult patients with at least a 6-month history of migraine were studied. Patients were instructed to treat within 1 hour of migraine onset, while pain was mild. Patients maintained a headache diary in which they rated their levels of pain and disability, and recorded other symptoms of migraine. Primary endpoints were pain freedom at 2 hours and sustained pain freedom at 24 hours post-dose. In TAME1, 57.3% versus 31.1% of patients reported pain freedom at 2 hours post-dose and 42.6% versus 23.2% reported 24-hour sustained pain freedom with rizatriptan versus placebo, respectively (P < .001 for both). In TAME2, 58.9% versus 31.1% of patients reported pain freedom at 2 hours post-dose and 48.0% versus 24.6% reported 24-hour sustained pain freedom with rizatriptan versus placebo, respectively (P < .001 for both). All other efficacy endpoints favored rizatriptan. Repeat doses of the medicine were not allowed; patients may have delayed treatment; non-migraine headaches may have been treated. Rizatriptan 10 mg was superior to placebo when treating migraine early, while pain is mild, as measured by pain freedom at 2 hours and 24-hour sustained pain freedom.Headache The Journal of Head and Face Pain 06/2006; 46(6):914-24. · 2.52 Impact Factor -
Article: Pharmacokinetic profile of rizatriptan 10-mg tablet and 10-mg orally disintegrating tablet administered with or without water in healthy subjects: an open-label, randomized, single-dose, 3-period crossover study.
[show abstract] [hide abstract]
ABSTRACT: This open-label, 3-period crossover study compared the plasma concentration profiles of rizatriptan tablet, orally disintegrating tablet with water (ODTc), and ODT without water (ODTs) in 24 healthy volunteers aged 18 to 45 years. At each period, subjects received a single dose of either 10-mg rizatriptan tablet, 10-mg rizatriptan ODTs, or 10-mg rizatriptan ODTc. The authors hypothesized that ODTc has a greater geometric mean AUC(0-2h) than ODTs and that ODTc has a greater geometric mean AUC(0-1h) than tablet. A secondary end point was to compare the time of occurrence of the maximum rizatriptan plasma concentration (t(max)) of each dosing method. ODTc had a statistically significantly greater geometric mean AUC(0-2h) compared with ODTs (33.84 h x ng/mL vs 18.83 h x ng/mL; P < .001). ODTc had a slightly, but not statistically significantly, greater geometric mean AUC(0-1h) compared with rizatriptan tablet (17.07 h x ng/mL vs 13.32 h x ng/mL). The median t(max) was 0.67 hours for ODTc and tablet and 1.33 hours for ODTs. ODTc showed a slightly, but not significantly, faster rate of absorption compared with tablet. ODTs with water had a faster rate of absorption than ODTc. Future studies are needed to determine whether this pharmacokinetic difference produces differential efficacy in a clinical setting.The Journal of Clinical Pharmacology 02/2006; 46(2):172-8. · 2.91 Impact Factor -
Article: Enoxaparin versus unfractionated heparin in patients treated with tirofiban, aspirin and an early conservative initial management strategy: results from the A phase of the A-to-Z trial.
[show abstract] [hide abstract]
ABSTRACT: In high risk patients with non-ST elevation acute coronary syndromes (ACS), enoxaparin is generally preferred to unfractionated heparin (UFH). However, less is known about the relative merits of these two forms of heparin in patients receiving concomitant glycoprotein IIb/IIIa inhibitors. The A phase of the A-to-Z trial was an open label non-inferiority trial in which 3987 patients with non-ST elevation ACS were randomised to receive either enoxaparin or UFH in combination with aspirin and tirofiban. Inclusion required either ST depression or cardiac biomarker elevation. While the selection of an early management strategy (invasive or conservative) was at the discretion of the local investigator, investigators were asked to designate their plans for an invasive or conservative strategy on the case record form. An early conservative strategy was specified for 1778 patients (45%); this subgroup forms the population for the present analyses. Among patients with a planned conservative strategy, baseline characteristics were similar between those randomised to UFH (n = 872) and those randomised to enoxaparin (n = 906). The primary endpoint of death, new MI, or documented refractory ischaemia within 7 days of randomisation occurred in 10.6% of patients randomised to UFH and 7.7% of patients randomised to enoxaparin (HR 0.72; 95% CI 0.53-0.99; p = 0.04). The combined rate of TIMI major, minor, or loss no-site bleeding was 1.3% in patients treated with UFH and 1.8% in those treated with enoxaparin (p = ns). When a conservative approach to catheterisation and PCI was planned for ACS patients receiving tirofiban and aspirin, enoxaparin was associated with superior efficacy and similar bleeding vs UFH.European Heart Journal 11/2004; 25(19):1688-94. · 10.48 Impact Factor -
Article: Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial.
[show abstract] [hide abstract]
ABSTRACT: Limited data are available evaluating how the timing and intensity of statin therapy following an acute coronary syndrome (ACS) event affect clinical outcome. To compare early initiation of an intensive statin regimen with delayed initiation of a less intensive regimen in patients with ACS. International, randomized, double-blind trial of patients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter (n = 2265) compared with ACS patients receiving placebo for 4 months followed by 20 mg/d of simvastatin (n = 2232), who were enrolled in phase Z of the A to Z trial between December 29, 1999, and January 6, 2003. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, readmission for ACS, and stroke. Follow-up was for at least 6 months and up to 24 months. Among the patients in the placebo plus simvastatin group, the median low-density lipoprotein (LDL) cholesterol level achieved while taking placebo was 122 mg/dL (3.16 mmol/L) at 1 month and was 77 mg/dL (1.99 mmol/L) at 8 months while taking 20 mg/d of simvastatin. Among the patients in the simvastatin only group, the median LDL cholesterol level achieved at 1 month while taking 40 mg/d of simvastatin was 68 mg/dL (1.76 mmol/L) and was 63 mg/dL (1.63 mmol/L) at 8 months while taking 80 mg/d of simvastatin. A total of 343 patients (16.7%) in the placebo plus simvastatin group experienced the primary end point compared with 309 (14.4%) in the simvastatin only group (40 mg/80 mg) (hazard ratio [HR], 0.89; 95% confidence interval [CI] 0.76-1.04; P =.14). Cardiovascular death occurred in 109 (5.4%) and 83 (4.1%) patients in the 2 groups (HR, 0.75; 95% CI, 0.57-1.00; P =.05) but no differences were observed in other individual components of the primary end point. No difference was evident during the first 4 months between the groups for the primary end point (HR, 1.01; 95% CI, 0.83-1.25; P =.89), but from 4 months through the end of the study the primary end point was significantly reduced in the simvastatin only group (HR, 0.75; 95% CI, 0.60-0.95; P =.02). Myopathy (creatine kinase >10 times the upper limit of normal associated with muscle symptoms) occurred in 9 patients (0.4%) receiving simvastatin 80 mg/d, in no patients receiving lower doses of simvastatin, and in 1 patient receiving placebo (P =.02). The trial did not achieve the prespecified end point. However, among patients with ACS, the early initiation of an aggressive simvastatin regimen resulted in a favorable trend toward reduction of major cardiovascular events.JAMA The Journal of the American Medical Association 10/2004; 292(11):1307-16. · 30.03 Impact Factor -
Article: Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin: a randomized controlled trial.
[show abstract] [hide abstract]
ABSTRACT: Enoxaparin or the combination of glycoprotein IIb/IIIa inhibitor tirofiban with unfractionated heparin independently have shown superior efficacy over unfractionated heparin alone in patients with non-ST-elevation acute coronary syndromes (ACS). It is not clear if combining enoxaparin with glycoprotein IIb/IIIa inhibitors is as safe or as effective as the current standard combination of unfractionated heparin with glycoprotein IIb/IIIa inhibitors. To assess efficacy and safety of the combination of enoxaparin and tirofiban compared with unfractionated heparin and tirofiban in patients with non-ST-elevation ACS. A prospective, international, open-label, randomized, noninferiority trial of 1 mg/kg of enoxaparin every 12 hours (n = 2026) compared with weight-adjusted intravenous unfractionated heparin (n = 1961) in patients with non-ST-elevation ACS receiving tirofiban and aspirin. Phase A of the A to Z trial was conducted between December 1999 and May 2002. Death, recurrent myocardial infarction, or refractory ischemia at 7 days in the intent-to-treat population with boundaries set for superiority and noninferiority. Safety based on measures of bleeding using the Thrombolysis in Myocardial Infarction (TIMI) classification system. A total of 169 (8.4%) of 2018 patients randomized to enoxaparin experienced death, myocardial infarction, or refractory ischemia at 7 days compared with 184 (9.4%) of 1952 patients randomized to unfractionated heparin (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.71-1.08). This met the prespecified criterion for noninferiority. All components of the composite primary and secondary end points favored enoxaparin except death, which occurred in only 1% of patients (23 for enoxaparin and 17 for unfractionated heparin). Rates for any TIMI grade bleeding were low (3.0% for enoxaparin and 2.2% for unfractionated heparin; P =.13). Using a worst-case approach that combined 2 independent bleeding evaluations, use of enoxaparin was associated with 1 additional TIMI major bleeding episode for each 200 patients treated. In patients receiving tirofiban and aspirin, enoxaparin is a suitable alternative to unfractionated heparin for treatment of non-ST-elevation ACS. The 12% relative and 1% absolute reductions in the primary end point in favor of enoxaparin met criterion for noninferiority and are consistent with prior trials performed without the use of glycoprotein IIb/IIIa inhibitors.JAMA The Journal of the American Medical Association 08/2004; 292(1):55-64. · 30.03 Impact Factor -
Article: Effect on high-density lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: results of the Comparative HDL Efficacy and Safety Study (CHESS).
[show abstract] [hide abstract]
ABSTRACT: Previous studies have shown that effects on high-density lipoprotein cholesterol (HDL-C) may differ among statins. A multicenter, randomized, double-blind, parallel-dose study was conducted in 917 hypercholesterolemic patients to compare the efficacy of 80 mg/d simvastatin versus 80 mg/d atorvastatin on HDL-C and apolipoprotein (apo) A-I for 24 weeks. Efficacy was assessed as the means of weeks 6 and 12 and weeks 18 and 24. Prespecified subgroups analyzed were patients with low HDL-C levels and with the metabolic syndrome. Simvastatin increased HDL-C and apo A-I values significantly more than did atorvastatin for the mean of weeks 6 and 12 (8.9% vs 3.6% and 4.9% vs -0.9%, respectively) and the mean of weeks 18 and 24 (8.3% vs 4.2% and 3.7% vs -1.4%). These differences were observed across both baseline HDL-C subgroups (<40 mg/dL, > or =40 mg/dL) and in patients with the metabolic syndrome. Low-density lipoprotein cholesterol and triglyceride reductions were greater with atorvastatin. Consecutive elevations >3x the upper limit of normal in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) occurred in significantly fewer patients treated with simvastatin than with atorvastatin (2/453 [0.4%] vs 13/464 [2.8%]), with most elevations observed in women taking atorvastatin (11/209 [5.3%] vs 1/199 [0.5%] for simvastatin). Simvastatin (80 mg) increased HDL-C and apo A-I significantly more than did atorvastatin (80 mg) in patients with hypercholesterolemia. This advantage was observed regardless of HDL-C level at baseline or the presence of the metabolic syndrome. Significantly fewer consecutive elevations >3x the upper limit of normal in ALT and/or AST occurred in patients receiving simvastatin.American heart journal 11/2003; 146(5):862-9. · 4.65 Impact Factor
Top co-authors
Top Journals
Institutions
-
2008
-
University of Cincinnati
Cincinnati, OH, USA
-
-
2006
-
DaVita Clinical Research
Minneapolis, MN, USA
-
