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 III, noninferiority clinical trial
DC Field | Value | Language |
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dc.contributor.author | Kim, Sung Ai | - |
dc.contributor.author | Park, Sungha | - |
dc.contributor.author | Chung, Namsik | - |
dc.contributor.author | Lim, Do-Sun | - |
dc.contributor.author | Yang, Joo-Young | - |
dc.contributor.author | Oh, Byung-Hee | - |
dc.contributor.author | Tahk, SeungJea | - |
dc.contributor.author | Ahn, Tae-Hoon | - |
dc.date.accessioned | 2021-09-09T09:08:36Z | - |
dc.date.available | 2021-09-09T09:08:36Z | - |
dc.date.created | 2021-06-10 | - |
dc.date.issued | 2008-05 | - |
dc.identifier.issn | 0149-2918 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/123702 | - |
dc.description.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 min 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 <90 mm Hg or whose SiDBP reduction was >= 10 mm Hg from baseline) after the 8-week treatment. Also, the incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs) were reported. 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 (3 1.1 %) 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 (3163 [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 non-inferior 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. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER | - |
dc.subject | PHARMACODYNAMIC CHARACTERISTICS | - |
dc.subject | CHIRAL SWITCHES | - |
dc.subject | ENANTIOMER | - |
dc.subject | EDEMA | - |
dc.subject | TOLERABILITY | - |
dc.subject | ANTAGONIST | - |
dc.subject | DRUGS | - |
dc.title | 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 III, noninferiority clinical trial | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lim, Do-Sun | - |
dc.identifier.doi | 10.1016/j.clinthera.2008.05.013 | - |
dc.identifier.scopusid | 2-s2.0-44849126989 | - |
dc.identifier.wosid | 000256824600006 | - |
dc.identifier.bibliographicCitation | CLINICAL THERAPEUTICS, v.30, no.5, pp.845 - 857 | - |
dc.relation.isPartOf | CLINICAL THERAPEUTICS | - |
dc.citation.title | CLINICAL THERAPEUTICS | - |
dc.citation.volume | 30 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 845 | - |
dc.citation.endPage | 857 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | PHARMACODYNAMIC CHARACTERISTICS | - |
dc.subject.keywordPlus | CHIRAL SWITCHES | - |
dc.subject.keywordPlus | ENANTIOMER | - |
dc.subject.keywordPlus | EDEMA | - |
dc.subject.keywordPlus | TOLERABILITY | - |
dc.subject.keywordPlus | ANTAGONIST | - |
dc.subject.keywordPlus | DRUGS | - |
dc.subject.keywordAuthor | amlodipine | - |
dc.subject.keywordAuthor | hypertension | - |
dc.subject.keywordAuthor | nicotinate | - |
dc.subject.keywordAuthor | racemic | - |
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