PMID- 19539099 OWN - NLM STAT- MEDLINE DCOM- 20090828 LR - 20131121 IS - 0149-2918 (Print) IS - 0149-2918 (Linking) VI - 31 IP - 5 DP - 2009 May TI - Efficacy and tolerability of two formulations of ramipril in Korean adults with mild to moderate essential hypertension: an 8-week, multicenter, prospective, randomized, open-label, parallel-group noninferiority trial. PG - 988-98 LID - 10.1016/j.clinthera.2009.05.020 [doi] AB - OBJECTIVE: This study was designed to compare the efficacy and tolerability of a new generic formulation of ramipril (test) and the branded formulation of ramipril (reference) to satisfy regulatory requirements for marketing of the generic product for use in Korean patients with mild to moderate hypertension. METHODS: This was an 8-week, multicenter, prospective, randomized, open-label, parallel-group non-inferiority trial in adult patients (age > 18 years) with mild to moderate essential hypertension (sitting dia-stolic blood pressure [SiDBP] 90-109 mm Hg). After a 2-week washout of previous antihypertensive medications, eligible patients were randomized to receive either ramipril 5 mg/d in the morning (low-dose group: baseline SiDBP 90-99 mm Hg) or ramipril 10 mg/d (high-dose group: baseline SiDBP 100-109 mm Hg) for the first 4 weeks. If SiDBP was > or = 90 mm Hg after 4 weeks of treatment, the dose was increased to 10 mg/d for the remaining 4 weeks in the low-dose group, and hydrochlorothiazide 12.5 mg was added to the regimen for the remaining 4 weeks in the high-dose group. The primary end point was the change in SiDBP from baseline to week 8. Secondary end points included a noninferiority analysis of the test and reference formulations with respect to the change in mean sitting systolic blood pressure (SiSBP) from baseline to week 8; SiDBP and SiSBP response rates (proportion of patients achieving an SiDBP < 90 mm Hg and SiSBP < 140 mm Hg, respectively) at 8 weeks; and changes from baseline in SiSBP, pulse wave velocity (PWV), exercise capacity, left-ventricular diastolic function (LVDF), and levels of brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP). Laboratory and clinical adverse events (AEs) were monitored at each study visit (4 and 8 weeks). RESULTS: The modified intent-to-treat population consisted of 89 patients (45 test, 44 reference; 60 men, 29 women; mean age, 49.7 years; mean weight, 69.9 kg). At week 8, mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (test: from 145.0 [9.7]/98.1 [5.3] mm Hg to 132.2 [11.1]/ 91.8 [7.1] mm Hg [P < 0.001]; reference: from 145.1 [11.4]/98.0 [5.7] mm Hg to 134.0 [14.6]/92.5 [7.9] mm Hg [P < 0.001]). The changes in blood pressure at week 8 did not differ significantly between the test and reference groups or between the low- and highdose groups in a subgroup analysis. Blood pressure response rates at 8 weeks did not differ significantly between the groups receiving the test and reference formulations (SiDBP: 26.7% and 31.8%, respectively; SiSBP: 37.8% and 40.9%). In addition, there were no significant between-group differences in the change in PWV (-63.8 and -38.7 cm/sec), LVDF at rest or after exercise, or levels of BNP or hs-CRP. The incidence of AEs was 64.4% in the test formulation group and 68.2% in the reference group formulation (P = NS). The most common AE in both groups was cough (10/45 [22.2%] and 10/44 [22.7%]). CONCLUSIONS: There were no significant differences in the efficacy and tolerability of the test and reference formulations of ramipril in these Korean adults with mild to moderate hypertension. The new generic formulation was noninferior to the reference formulation in terms of the change in SiDBP at week 8. FAU - Kim, Sang-Hyun AU - Kim SH AD - Department of Internal Medicine, Seoul Metropolitan Boramae Hospital, Seoul, Republic of Korea. FAU - Chung, Woo-Young AU - Chung WY FAU - Zo, Joo-Hee AU - Zo JH FAU - Kim, Myung-A AU - Kim MA FAU - Chang, Hyuk-Jae AU - Chang HJ FAU - Cho, Young-Seok AU - Cho YS FAU - Youn, Tae-Jin AU - Youn TJ FAU - Chae, In-Ho AU - Chae IH FAU - Choi, Dong-Joo AU - Choi DJ FAU - Gwak, Jae-Jin AU - Gwak JJ FAU - Lee, Hae-Young AU - Lee HY FAU - Park, Jin-Sik AU - Park JS FAU - Kang, Hyun-Jae AU - Kang HJ FAU - Kim, Young-Jin AU - Kim YJ FAU - Kim, Hyo-Soo AU - Kim HS LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Antihypertensive Agents) RN - 0 (Drugs, Generic) RN - 0J48LPH2TH (Hydrochlorothiazide) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 9007-41-4 (C-Reactive Protein) RN - L35JN3I7SJ (Ramipril) SB - IM MH - Antihypertensive Agents/adverse effects/*therapeutic use MH - Blood Pressure/drug effects MH - C-Reactive Protein/drug effects MH - Chemistry, Pharmaceutical MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Drugs, Generic/adverse effects/*therapeutic use MH - Female MH - Humans MH - Hydrochlorothiazide/therapeutic use MH - Hypertension/*drug therapy MH - Korea MH - Male MH - Middle Aged MH - Natriuretic Peptide, Brain/blood/drug effects MH - Prospective Studies MH - Ramipril/adverse effects/*chemistry/classification/*therapeutic use MH - Severity of Illness Index MH - Treatment Outcome MH - Ventricular Function, Left/drug effects EDAT- 2009/06/23 09:00 MHDA- 2009/08/29 09:00 CRDT- 2009/06/23 09:00 PHST- 2009/03/13 00:00 [accepted] PHST- 2009/06/23 09:00 [entrez] PHST- 2009/06/23 09:00 [pubmed] PHST- 2009/08/29 09:00 [medline] AID - S0149-2918(09)00166-0 [pii] AID - 10.1016/j.clinthera.2009.05.020 [doi] PST - ppublish SO - Clin Ther. 2009 May;31(5):988-98. doi: 10.1016/j.clinthera.2009.05.020.