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

• Published in: Clinical therapeutics 2015-08, Vol.37 (8), p.1726-1739
• Main Authors: Na, Sang-Hoon, MD, PhD, Lee, Hae-Young, MD, PhD, Hong Baek, Sang, MD, PhD, Jeon, Hui-Kyung, MD, PhD, Kang, Jin-Ho, MD, PhD, Kim, Yoon-Nyun, MD, PhD, Park, Chang-Gyu, MD, PhD, Ryu, Jae-Kean, MD, PhD, Rhee, Moo-Yong, MD, PhD, Kim, Moo-Hyun, MD, PhD, Hong, Taek-Jong, MD, PhD, Choi, Dong-Ju, MD, PhD, Cho, Seong-Wook, MD, PhD, Cha, Dong-Hun, MD, PhD, Jeon, Eun-Seok, MD, PhD, Kim, Jae-Joong, MD, PhD, Shin, Joon-Han, MD, PhD, Park, Sung-Ha, MD, PhD, Lee, Seung-Hwan, MD, PhD, John, Sung-Hee, MD, PhD, Shin, Eun-Seok, MD, PhD, Kim, Nam-Ho, MD, PhD, Lee, Sung-Yun, MD, PhD, Kwan, Jun, MD, PhD, Jeong, Myung-Ho, MD, PhD, Kim, Sang-Wook, MD, PhD, Jeong, Jin-Ok, MD, PhD, Kim, Dong-Woon, MD, PhD, Lee, Nam-Ho, MD, PhD, Park, Woo-Jung, MD, PhD, Ahn, Jeong-Cheon, MD, PhD, Won, Kyung-Heon, MD, PhD, Uk Lee, Seung, MD, PhD, Cho, Jang-Hyun, MD, PhD, Kim, Soon-Kil, MD, PhD, Ahn, Taehoon, MD, PhD, Hong, Sukkeun, MD, PhD, Yoo, Sang-Yong, MD, PhD, Kim, Song-Yi, MD, Kim, Byung-Soo, MD, PhD, Juhn, Jae-Hyeon, PhD, Kim, Sun-Young, MS, Lee, Yu-Jeong, MS, Oh, Byung-Hee, MD, PhD
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Adult; Aged; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - adverse effects; Antihypertensive Agents - therapeutic use; Blood Pressure - drug effects; Clinical trials; combination; Dihydropyridines - adverse effects; Dihydropyridines - therapeutic use; Dizziness - chemically induced; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug dosages; Essential Hypertension; Female; Headache - chemically induced; Humans; Hypertension; Hypertension - drug therapy; Hypertension - physiopathology; Internal Medicine; lercanidipine; Male; Medical Education; Middle Aged; Response rates; Substance abuse treatment; Treatment Outcome; valsartan; Valsartan - administration & dosage; Valsartan - adverse effects; Valsartan - therapeutic use; Young Adult
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2015.05.512

Abstract Purpose 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). Findings 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 incidence