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Byunghee Oh - One of the best experts on this subject based on the ideXlab platform.
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quantification of pedal edema during treatment with s Amlodipine nicotinate versus Amlodipine besylate in female korean patients with mild to moderate hypertension a 12 week multicenter randomized double blind active controlled phase iv clinical trial
2012Co-Authors: Gyuchul Oh, Hyunjae Kang, Joohee Zo, Dongju Choi, Byunghee OhAbstract:Abstract Background Amlodipine is a racemic mixture of (R)- and (S)-enantiomers. It has been suggested that removing the therapeutically inactive (R)-enantiomer will reduce adverse events while preserving the agent's efficacy. Women experience more adverse effects from Amlodipine. Objective This exploratory study compared the amount of pedal edema experienced by female Korean patients with mild to moderate hypertension when receiving S(-)-Amlodipine nicotinate compared with Amlodipine besylate. Methods This study was a 12-week, multicenter, randomized, double-blind, active-controlled, Phase IV clinical trial. Female patients with mild to moderate hypertension were randomly assigned to receive either S(-)-Amlodipine nicotinate 2.5 to 5 mg once daily or Amlodipine besylate 5 to 10 mg once daily for 12 weeks. The primary objective was to compare the change in ankle–foot volume quantified by using a water displacement method after 12 weeks of therapy. The secondary objectives were to compare the changes in mean sitting systolic and diastolic blood pressures. Safety assessment included monitoring all laboratory tests, adverse events (AEs), serious AEs, and possible relation to the study medication. Results Of the 38 patients enrolled, 17 patients in each group were eligible for final analysis. In the S(-)-Amlodipine nicotinate group, the mean ankle–foot volume at baseline was 1056.91 (98.15) mL, and volume after 12 weeks of treatment was 1016.68 (158.37) mL, a decrease of 40.24 (110.05) mL. In the Amlodipine besylate group, mean ankle–foot volume at baseline was 1037.56 (158.30) mL, and volume after treatment was 1067.59 (152.54) mL, an increase of 30.03 (69.59) mL. There was a significant difference in the change of ankle–foot volume between the 2 groups (–70.26 mL [95% CI, –134.60 to –5.94], P = 0.028). After 12 weeks, the mean changes in sitting systolic blood pressure from baseline were not significantly different between the 2 groups (–21.82 [8.76] vs –26.82 [11.89] mm Hg; P = 0.172). Changes in mean sitting diastolic blood pressure also were not significant (–14.71 [6.94] vs –10.88 [5.81] mm Hg; P = 0.091). One patient in each group had facial edema, and another patient in the Amlodipine besylate group had facial flushing. Overall, there was no significant difference in drug-related AEs between the 2 groups ( P = 0.999). Conclusions These female Korean patients with hypertension taking S(-)-Amlodipine nicotinate had less ankle edema, with no significant difference in BP-lowering efficacy, compared with those taking Amlodipine besylate. S(-)-Amlodipine nicotinate may be a suitable alternative for patients intolerant to Amlodipine besylate. (Clinical Research Information Service: CRiS, KCT0000450).
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efficacy and safety profiles of a new s Amlodipine nicotinate formulation versus racemic Amlodipine besylate in adult korean patients with mild to moderate hypertension an 8 week multicenter randomized double blind double dummy parallel group phase i
2008Co-Authors: Sungha Park, Joo Young Yang, Byunghee Oh, Namsik Chung, Seung-jea TahkAbstract:Abstract Background: "Chiral switching" from an existing racemate to a pure enantiomeric compound is a popular theme in drug development, especially when the enantiomer is found to have better efficacy and safety profiles. Amlodipine is a racemic mixture, composed of the S (-)-enantiomer, which is the pharmacologically active isomer, and the R (+)-enantiomer, which is 1000-fold less active. S (-)-Amlodipine nicotinate, a chirally switched form of Amlodipine nicotinate, has been developed and found to be bioequivalent to Amlodipine besylate in Phase I clinical trials in Korea. Objective: The aim of this study was to compare the efficacy and safety profiles of S (-)-Amlodipine nicotinate with those of Amlodipine besylate in adult Korean patients with mild to moderate hypertension (diastolic blood pressure [DBP] ≥90 mm Hg and ≤109 mm Hg). Methods: This was an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group, Phase III, noninferiority clinical trial. After an initial 2-week placebo run-in period, patients aged 18 to 75 years with sitting DBP (SiDBP) ≥90 and ≤109 mm Hg at day 0 (baseline) were randomly allocated to receive S (-)-Amlodipine nicotinate 2.5 mg QD or Amlodipine besylate 5 mg QD for 8 weeks. The dose of study medication was doubled after 4 weeks in patients who had not responded to treatment (SiDBP ≥90 mm Hg). The primary end point was noninferiority of the difference in mean SiDBP from baseline to week 8 for S (-)-Amlodipine nicotinate compared with Amlodipine besylate. Secondary end points were as follows: (1) noninferiority of the difference in mean sitting systolic blood pressure (SiSBP) from baseline to week 8 between the study groups; and (2) SiDBP response rate (defined as the proportion of patients whose SiDBP was Severe AEs/ADRs were defined as those associated with any of the following: death; an event associated with a high risk of mortality; an event requiring hospitalization; or development of a permanent disability or congenital malformation. Results: One hundred fifty-seven patients were assessed for inclusion in the study. Of these, 124 patients were randomly allocated to receive S (-)-Amlodipine nicotinate (42 men, 21 women; mean [SD] age, 52.4 [10.3] years [range, 23–70 years]; weight, 67.7 [10.8] kg [range, 44–92 kg]) or Amlodipine besylate (45 men, 16 women; mean [SD] age, 54.5 [10.0] years [range, 30-73]; weight, 68.9 [9.8] kg [range, 49–95 kg]). One hundred sixteen patients completed the study, but 11 patients (8.9%) were dropped from the per-protocol analysis due to violations; therefore, 105 patients were included in the modified intent-to-treat population analysis ( S [-]-Amlodipine nicotinate, 55 patients; Amlodipine besylate, 50 patients). There were no significant between-group differences in the baseline characteristics. Baseline mean (SD) SiSBP and SiDBP were 142.6 (11.3) and 94.9 (4.8) mm Hg in the S (-)-Amlodipine nicotinate group, and 141.8 (8.3) and 96.1 (4.9) mm Hg in the Amlodipine besylate group. Mean (SD) changes in SiSBP were 17.6 (11.2) mm Hg in the S (-)-Amlodipine nicotinate group and 18.6 (12.3) mm Hg in the Amlodipine besylate group. The SiDBP response rates were 92.7% in the S (-)-Amlodipine nicotinate group and 88.0% in the Amlodipine besylate group. There were no significant between-group differences in the prevalence of AEs and ADRs. In the S(-)-Amlodipine nicotinate group, 15 patients (23.8%) reported a total of 28 AEs, and 19 patients (31.1%) reported a total of 27 AEs in the Amlodipine besylate group. Six patients (9.5%) in the S (-)-Amlodipine nicotinate group and 7 patients (11.4%) in the Amlodipine besylate group experienced a total of 19 ADRs (11 and 8, respectively). The most common ADRs were liver enzyme elevation (3/63 [4.8%]) in the S (-)-Amlodipine nicotinate group and facial flushing (3/61 [4.9%]) in the Amlodipine besylate group. No cases of severe AEs or ADRs were reported in either group. Conclusions: The reduction of SiDBP after 8 weeks of treatment with S (-)-Amlodipine nicotinate was noninferior compared with that of racemic Amlodipine besylate in these adult Korean patients with mild to moderate hypertension. The SiDBP response rate and the reduction of SiSBP after 8 weeks of treatment with S (-)-Amlodipine nicotinate were not significantly different from those with racemic Amlodipine besylate. Both treatments were generally well tolerated.
Myeong Ho Yoon - One of the best experts on this subject based on the ideXlab platform.
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comparison of efficacy and tolerability of Amlodipine orotate versus Amlodipine besylate in adult patients with mild to moderate hypertension a multicenter randomized double blind placebo controlled parallel group 8 week follow up noninferiority tria
2006Co-Authors: Soon Jun Hong, Hyee Kyoung Jeon, Jun Kyun, Sang Hong Baek, Myeong Ho YoonAbstract:Abstract Objective: The purpose of this study was to compare the efficacy and tolerability of Amlodipine orotate with those of Amlodipine besylate in Korean patients with mild to moderate hypertension. Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study was designed as a noninferiority study. To be included in the study, previously untreated patients had to have a sitting diastolic blood pressure (SiDBP) of 90 to 109 mm Hg. Previously treated patients had to discontinue their current annhypertensive medications and have a baseline SiDBP between 90 and 109 mm Hg after a 2-week washout period. Patients who met the inclusion criteria were randomly assigned to receive 5 mg Amlodipine orotate or 5 mg Amlodipine besylate for 8 weeks. The medication dose was doubled (10 mg QD for either Amlodipine orotate or Amlodipine besylate) 4 weeks after enrollment if SiDBP was ≥90 mm Hg. The primary efficacy analysis was noninferiority of the difference in mean trough SiDBP changes from baseline for amlodipin eorotate as compared with Amlodipine besylate after 8 weeks of treatment. For the secondary efficacy analysis, 2 other measures were analyzed after 8 weeks of treatment. The SiDBP response rate was defined as an SiDBP measurement Results: Eligible patients (n = 109; 43 women and 66 men) were randomly assigned to receive Amlodipine orotate (n = 53) or Amlodipine besylate (n = 56). No significant differences were found in sex, age, weight, or current smoking between the groups (all, P = NS). The proportion of patients with previous antihypertensive medications was not different between the groups (47.2% [25/53] in the Amlodipine orotate group and 50.0% [28/56] in the Amlodipine besylate group; P = NS). No significant differences were found in baseline SiDBP (mean [SD], 100 [6] mm Hg [range, 90–109 mm Hg] in the Amlodipine orotate group and 100 [6] mm Hg [range, 90–108 mm Hg] in the Amlodipine besylate group; P = NS) or in baseline SiSBP (mean [SD], 149 [14] mm Hg [range, 125–179 mm Hg] in the Amlodipine orotate group and 146 [10] mm Hg [range, 123–167 mm Hg] in the Amlodipine besylate group; p = NS). The mean (SD) changes in SiDBP were −15.6 (6.3) mm Hg for the Amlodipine orotate group and −14.5 (5.5) mm Hg for the Amlodipine besylate groups was 1.1 (5.9) mm Hg (95% CI, −0.87 to ∞), and because the lower boundary of the 95% CI was greater than −5 mm Hg, Amlodipine orotate was considered noninferior to Amlodipine besylate. The response rate was 48 of 51 (94.1%) in the Amlodipine orotate group compared with 50 (92.6%) of 54 in the Amlodipine besylate group after 8 weeks of treatment ( P = NS). The mean (SD) compliance rates were 97.6% (3.6%) in the Amlodipine orotate group and 96.5% (4.3%) in the Amlodipine besylate group ( P = NS). The incidence of drug-related adverse events (AEs) was similar between the groups (1/53 [1.9%]) in the Amlodipine orotate group vs 4/55 [7.3%] in the Amlodipine besylate group; P = NS). The most common drug-related AE overall was peripheral edema (2/55 [3.6%]), and the most common of all the AEs was upper respiratory tract infection (4/55 [7.3%]) in the Amlodipine besylate group. The most common drug-related AE was headache (1/53 [1.9%]) in the Amlodipine orotate group and peripheral edema (2/55 [3.6%]) in the Amlodipine besylate group. No severe AEs were found in either group. Conclusion: The reduction in SiDBP after 8 weeks of Amlodipine orotate treatment was noninferior to that of Amlodipine besylate in these Korean patients with mild to moderate hypertension. The SiDBP response rate and the reduction in SISBP after 8 weeks of Amlodipine orotate treatment were not significantly different from those of Amlodipine besylate treatment. Both agents were wel tolerated.
Rainer Pospiech - One of the best experts on this subject based on the ideXlab platform.
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two multicenter 8 week randomized double blind placebo controlled parallel group studies evaluating the efficacy and tolerability of Amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension
2007Co-Authors: Thomas Philipp, Timothy R Smith, Robert Glazer, Margaret Wernsing, Joseph Yen, James Jin, Helmut Schneider, Rainer PospiechAbstract:Abstract Background: Patients with hypertension may require combination therapy to attain the blood pressure targets recommended by US and European treatment guidelines. Combination therapy with a calcium channel blocker and an angiotensin II-receptor blocker would be expected to provide enhanced efficacy. Objectives: Two studies were conducted to compare the efficacy of various combinations of Amlodipine and valsartan administered once daily with their individual components and placebo in patients with mild to moderate essential hypertension (mean sitting diastolic blood pressure [ MSDBP ] ≥95 and Methods: The 2 studies were multinational, multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group trials. In study 1, patients were randomized to receive Amlodipine 2.5 or 5 mg once daily, valsartan 40 to 320 mg once daily, the combination of Amlodipine 2.5 or 5 mg with valsartan 40 to 320 mg once daily, or placebo. In study 2, patients were randomized to receive Amlodipine 10 mg once daily, valsartan 160 or 320 mg once daily, the combination of Amlodipine 10 mg with valsartan 160 or 320 mg once daily, or placebo. The primary efficacy variable in both studies was change from baseline in MSDBP at the end of the study. Secondary variables included the change in mean sitting systolic blood pressure (MSSBP), response rate (the proportion of patients achieving an MSDBP Results: A total of 1911 patients were randomized to treatment in study 1 (1022 Amlodipine + valsartan; 507 valsartan; 254 Amlodipine; 128 placebo); 1250 were randomized to treatment in study 2 (419, 415, 207, and 209, respectively). In all treatment groups in both studies, the majority of patients were white (79.5% study 1, 79.4% study 2) and male (53.5% and 50.3%, respectively). The overall mean age was 54.4 years in study 1 and 56.9 years in study 2. The mean weight of patients in study 1 was higher than that in study 2 (88.8 vs 79.7 kg). The overall baseline mean sitting BP was 152.8/99.3 mm Hg in study 1 and 156.7/99.1 mm Hg in study 2. With the exception of a few combinations that included Amlodipine 2.5 mg, the combination regimens in both studies were associated with significantly greater reductions in MSDBP and MSSBP compared with their individual components and placebo ( P P = 0.014), was significantly higher compared with valsartan monotherapy (2.1%; P Conclusions: In these adult patients with mild to moderate hypertension, the combination of Amlodipine + valsartan was associated with significantly greater blood pressure reductions from baseline compared with Amlodipine or valsartan monotherapy or placebo. The incidence of peripheral edema was significantly lower with combination therapy than with Amlodipine monotherapy.
Philip J Saul - One of the best experts on this subject based on the ideXlab platform.
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a randomized placebo controlled trial of Amlodipine in children with hypertension
2004Co-Authors: Joseph T Flynn, Jane W Newburger, Stephen R Daniels, Stephen P Sanders, Ronald J Portman, Ronald J Hogg, Philip J SaulAbstract:Abstract Objectives Evaluation of the efficacy and safety of Amlodipine in hypertensive children. Study design A randomized, double blinded, placebo-controlled, parallel-group, dose-ranging study was conducted at 49 centers in North and South America. The primary end point was the effect of Amlodipine on systolic blood pressure (BP); secondary end points included the effect of Amlodipine on diastolic BP, the effect of Amlodipine as a function of dose and body size, and evaluation of safety. Results We enrolled 268 hypertensive children (mean age, 12.1 ± 3.3 years); 84 (31.3%) had primary hypertension, and 177 (66%) were boys. Amlodipine produced significantly greater reductions in systolic BP than placebo; these were −6.9 mm Hg for 2.5 mg daily ( P =.045 vs placebo) and −8.7 mm Hg for 5 mg daily ( P =.005 vs placebo). The underlying cause of hypertension had no effect on the response to Amlodipine. There was a significant dose-response effect of Amlodipine on both systolic and diastolic BP beginning at doses ≥0.06 mg/kg per day. Systolic BP ≤95 th percentile was achieved in 34.6% of subjects with systolic hypertension. Amlodipine was well tolerated, with just 6 children withdrawn from treatment because of drug-related adverse events. Conclusions Amlodipine effectively lowers systolic BP in a dose-dependent manner in hypertensive children who require drug treatment.
Seung-jea Tahk - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety profiles of a new s Amlodipine nicotinate formulation versus racemic Amlodipine besylate in adult korean patients with mild to moderate hypertension an 8 week multicenter randomized double blind double dummy parallel group phase i
2008Co-Authors: Sungha Park, Joo Young Yang, Byunghee Oh, Namsik Chung, Seung-jea TahkAbstract:Abstract Background: "Chiral switching" from an existing racemate to a pure enantiomeric compound is a popular theme in drug development, especially when the enantiomer is found to have better efficacy and safety profiles. Amlodipine is a racemic mixture, composed of the S (-)-enantiomer, which is the pharmacologically active isomer, and the R (+)-enantiomer, which is 1000-fold less active. S (-)-Amlodipine nicotinate, a chirally switched form of Amlodipine nicotinate, has been developed and found to be bioequivalent to Amlodipine besylate in Phase I clinical trials in Korea. Objective: The aim of this study was to compare the efficacy and safety profiles of S (-)-Amlodipine nicotinate with those of Amlodipine besylate in adult Korean patients with mild to moderate hypertension (diastolic blood pressure [DBP] ≥90 mm Hg and ≤109 mm Hg). Methods: This was an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group, Phase III, noninferiority clinical trial. After an initial 2-week placebo run-in period, patients aged 18 to 75 years with sitting DBP (SiDBP) ≥90 and ≤109 mm Hg at day 0 (baseline) were randomly allocated to receive S (-)-Amlodipine nicotinate 2.5 mg QD or Amlodipine besylate 5 mg QD for 8 weeks. The dose of study medication was doubled after 4 weeks in patients who had not responded to treatment (SiDBP ≥90 mm Hg). The primary end point was noninferiority of the difference in mean SiDBP from baseline to week 8 for S (-)-Amlodipine nicotinate compared with Amlodipine besylate. Secondary end points were as follows: (1) noninferiority of the difference in mean sitting systolic blood pressure (SiSBP) from baseline to week 8 between the study groups; and (2) SiDBP response rate (defined as the proportion of patients whose SiDBP was Severe AEs/ADRs were defined as those associated with any of the following: death; an event associated with a high risk of mortality; an event requiring hospitalization; or development of a permanent disability or congenital malformation. Results: One hundred fifty-seven patients were assessed for inclusion in the study. Of these, 124 patients were randomly allocated to receive S (-)-Amlodipine nicotinate (42 men, 21 women; mean [SD] age, 52.4 [10.3] years [range, 23–70 years]; weight, 67.7 [10.8] kg [range, 44–92 kg]) or Amlodipine besylate (45 men, 16 women; mean [SD] age, 54.5 [10.0] years [range, 30-73]; weight, 68.9 [9.8] kg [range, 49–95 kg]). One hundred sixteen patients completed the study, but 11 patients (8.9%) were dropped from the per-protocol analysis due to violations; therefore, 105 patients were included in the modified intent-to-treat population analysis ( S [-]-Amlodipine nicotinate, 55 patients; Amlodipine besylate, 50 patients). There were no significant between-group differences in the baseline characteristics. Baseline mean (SD) SiSBP and SiDBP were 142.6 (11.3) and 94.9 (4.8) mm Hg in the S (-)-Amlodipine nicotinate group, and 141.8 (8.3) and 96.1 (4.9) mm Hg in the Amlodipine besylate group. Mean (SD) changes in SiSBP were 17.6 (11.2) mm Hg in the S (-)-Amlodipine nicotinate group and 18.6 (12.3) mm Hg in the Amlodipine besylate group. The SiDBP response rates were 92.7% in the S (-)-Amlodipine nicotinate group and 88.0% in the Amlodipine besylate group. There were no significant between-group differences in the prevalence of AEs and ADRs. In the S(-)-Amlodipine nicotinate group, 15 patients (23.8%) reported a total of 28 AEs, and 19 patients (31.1%) reported a total of 27 AEs in the Amlodipine besylate group. Six patients (9.5%) in the S (-)-Amlodipine nicotinate group and 7 patients (11.4%) in the Amlodipine besylate group experienced a total of 19 ADRs (11 and 8, respectively). The most common ADRs were liver enzyme elevation (3/63 [4.8%]) in the S (-)-Amlodipine nicotinate group and facial flushing (3/61 [4.9%]) in the Amlodipine besylate group. No cases of severe AEs or ADRs were reported in either group. Conclusions: The reduction of SiDBP after 8 weeks of treatment with S (-)-Amlodipine nicotinate was noninferior compared with that of racemic Amlodipine besylate in these adult Korean patients with mild to moderate hypertension. The SiDBP response rate and the reduction of SiSBP after 8 weeks of treatment with S (-)-Amlodipine nicotinate were not significantly different from those with racemic Amlodipine besylate. Both treatments were generally well tolerated.