title: Evaluation of the Efficacy and Safety of the Lercanidipine/Valsartan Combination in Korean Patients With Essential Hypertension Not Adequately Controlled With Lercanidipine Monotherapy: A Randomized, Multicenter, Parallel Design, Phase III Clinical Trial.
abstract: OBJECTIVE
  The objective of this study was to evaluate the efficacy and safety of the lercanidipine/valsartan combination compared with lercanidipine monotherapy in patients with hypertension.
  
  
  METHODS
  Part 1 of this study was the randomized, multicenter, double-blind, parallel group, Phase III, 8-week clinical trial to compare superiority of lercanidipine 10 mg/valsartan 80 mg (L10/V80) and lercanidipine 10 mg/valsartan 160 mg (L10/V160) combinations with lercanidipine 10 mg (L10) monotherapy. At screening, hypertensive patients, whose diastolic blood pressure (DBP) was >90 mm Hg after 4 weeks with L10, were randomized to 3 groups of L10, L10/V80, and L10/V160. The primary end point was the change in the mean sitting DBP from baseline (week 0) after 8 weeks of therapy. Patients who were randomly assigned to L10/V160 and whose mean DBP was still ≥ 90 mm Hg in part 1 were enrolled to the up-titration extension study with lercanidipine 20 mg/valsartan 160 mg (L20/V160) (part 2).
  
  
  RESULTS
  Of 772 patients screened, 497 were randomized to 3 groups (166 in the L10 group, 168 in the L10/V80 group, and 163 in the L10/V160 group). Mean (SD) age was 55 (9.9) years, and male patients comprised 69%. The mean (SD) baseline systolic blood pressure (SBP)/DBP were 148.4 (15.1)/94.3 (9.5) mm Hg. No significant differences were found between groups in baseline characteristics except the percentages of previous history of antihypertensive medication. The primary end points, the changes of mean (SD) DBP at week 8 from the baseline were -2.0 (8.8) mm Hg in the L10 group, -6.7 (8.5) mm Hg in L10/V80 group, and -8.1 (8.4) mm Hg in L10/V160 group. The adjusted mean difference between the combination groups and the L10 monotherapy group was -4.6 mm Hg (95% CI, -6.5 to -2.6; P < 0.001) in the L10/V80 group and -5.9 mm Hg (95% CI, -7.9 to -4.0, P < 0.001) in the L10/V160 group, which had significantly greater efficacy in BP lowering. A total of 74 patients were enrolled in the part 2 extension study. Changes of mean (SD) DBP and SBP from week 8 to week 12 and week 16 were -5.6 (7.9)/-8.0 (12.0) mm Hg and -5.5 (7.0)/-8.5 (11.3) mm Hg, respectively. For evaluation of the safety profile, the frequencies of adverse events between groups were also not significantly different. The most frequently reported adverse events were headache (6 cases, 20.7%) in the L10 group, dizziness (8 cases, 16.3%) in L10/V80 group, and nasopharyngitis (3 cases, 9.4%) in L10/V160 group, and the incidences of adverse events were not different between groups.
  
  
  CONCLUSIONS
  Treatment of L10/V80 or L10/V160 combination therapy resulted in significantly greater BP lowering compared with L10 monotherapy. Moreover, the L20/V160 high dose combination had additional BP lowering effect compared with nonresponders with the L10/V160 combination. ClinicalTrials.gov: NCT01928628.
authors.affiliation: Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Na
authors.affiliation: Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sang
authors.initials: S
authors.lastname: Hong Baek
authors.affiliation: Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hui-Kyung
authors.initials: HK
authors.lastname: Jeon
authors.affiliation: Kangbuk Samsung Hospital, Seoul, Korea.
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Keimyung University, Dongsan Medical Center, Seoul, Korea.
authors.forename: Yoon-Nyun
authors.initials: YN
authors.lastname: Kim
authors.affiliation: Korea University Guro Hospital, Seoul, Korea.
authors.forename: Chang-Gyu
authors.initials: CG
authors.lastname: Park
authors.affiliation: Daegu Catholic University Medical Center, Seoul, Korea.
authors.forename: Jae-Kean
authors.initials: JK
authors.lastname: Ryu
authors.affiliation: Dongguk University Ilsan Hospital, Seoul, Korea.
authors.forename: Moo-Yong
authors.initials: MY
authors.lastname: Rhee
authors.affiliation: Dong-A University Hospital, Seoul, Korea.
authors.forename: Moo-Hyun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Pusan National University Hospital, Seoul, Korea.
authors.forename: Taek-Jong
authors.initials: TJ
authors.lastname: Hong
authors.affiliation: Seoul National University Bundang Hospital, Seoul, Korea.
authors.forename: Dong-Ju
authors.initials: DJ
authors.lastname: Choi
authors.affiliation: Bundang Jesaeng Hospital, Seoul, Korea.
authors.forename: Seong-Wook
authors.initials: SW
authors.lastname: Cho
authors.affiliation: CHA University Bundang CHA Hospital, Seoul, Korea.
authors.forename: Dong-Hun
authors.initials: DH
authors.lastname: Cha
authors.affiliation: Samsung Medical Center, Seoul, Korea.
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Jeon
authors.affiliation: Asan Medical Center, College of Medicine, Ulsan University, Seoul, Korea.
authors.forename: Jae-Joong
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Ajou University Hospital, Seoul, Korea.
authors.forename: Joon-Han
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Yonsei University College of Medicine Severance Hospital, Seoul, Korea.
authors.forename: Sung-Ha
authors.initials: SH
authors.lastname: Park
authors.affiliation: Wonju Severance Christian Hospital, Seoul, Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Presbyterian Medical Center, Seoul, Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: John
authors.affiliation: Ulsan University Hospital, Seoul, Korea.
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Shin
authors.affiliation: Wonkwang University Hospital, Seoul, Korea.
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Inje University Ilsan-Paik Hospital, Seoul, Korea.
authors.forename: Sung-Yun
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Inha University Hospital, Seoul, Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Kwan
authors.affiliation: Chonnam National University Hospital, Seoul, Korea.
authors.forename: Myung-Ho
authors.initials: MH
authors.lastname: Jeong
authors.affiliation: Chung-Ang University Hospital, Seoul, Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Chungnam National University Hospital, Seoul, Korea.
authors.forename: Jin-Ok
authors.initials: JO
authors.lastname: Jeong
authors.affiliation: Chungbuk National University Hospital, Seoul, Korea.
authors.forename: Dong-Woon
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea.
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Lee
authors.affiliation: Hallym University Sacred Heart Hospital, Seoul, Korea.
authors.forename: Woo-Jung
authors.initials: WJ
authors.lastname: Park
authors.affiliation: Korea University Ansan Hospital, Seoul, Korea.
authors.forename: Jeong-Cheon
authors.initials: JC
authors.lastname: Ahn
authors.affiliation: Seoul Medical Center, Seoul, Korea.
authors.forename: Kyung-Heon
authors.initials: KH
authors.lastname: Won
authors.affiliation: Kwangju Christian Hospital, Seoul, Korea.
authors.forename: Seung
authors.initials: S
authors.lastname: Uk Lee
authors.affiliation: St. Carollo Hospital, Seoul, Korea.
authors.forename: Jang-Hyun
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Hanyang University Guri Hospital, Seoul, Korea.
authors.forename: Soon-Kil
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Gachon University Gil Hospital, Seoul, Korea.
authors.forename: Taehoon
authors.initials: T
authors.lastname: Ahn
authors.affiliation: Sejong General Hospital, Seoul, Korea.
authors.forename: Sukkeun
authors.initials: S
authors.lastname: Hong
authors.affiliation: Gangneng Asan Hospital, Seoul, Korea.
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Yoo
authors.affiliation: Jeju National University Hospital, Seoul, Korea.
authors.forename: Song-Yi
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Dae Dong Hospital, Seoul, Korea. Electronic address: ohbhmed@snu.ac.kr.
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: LG Life Sciences Ltd, Seoul, Korea.
authors.forename: Jae-Hyeon
authors.initials: JH
authors.lastname: Juhn
authors.affiliation: LG Life Sciences Ltd, Seoul, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: LG Life Sciences Ltd, Seoul, Korea.
authors.forename: Yu-Jeong
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Byung-Hee
authors.initials: BH
authors.lastname: Oh
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004095:Dihydropyridines / Q000009:adverse effects / Q000627:therapeutic use*; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D000075222:Essential Hypertension; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D000068756:Valsartan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D004095:Dihydropyridines; D004338:Drug Combinations; D000068756:Valsartan; C060343:lercanidipine
keywords: combination; hypertension; lercanidipine; valsartan