Open clinical studies on a new angiotensin II receptor antagonist, TCV 116.
OBJECTIVE
The goals of these preliminary studies were to evaluate the effects of a new angiotensin II receptor antagonist, TCV 116, on the daytime blood pressure profile in hospital inpatients with essential hypertension, and to evaluate the clinical efficacy and safety of this agent in outpatients with essential hypertension.


METHODS
In study 1, daytime blood pressure changes were studied in 28 inpatients with mild to moderate essential hypertension (systolic blood pressure > or = 150 mmHg, diastolic blood pressure > or = 90 mmHg). In study 2, 55 outpatients with essential hypertension (systolic blood pressure > or = 160 mmHg, diastolic blood pressure > or = 95 mmHg) were enrolled in a dose-finding study.


METHODS
In study 1, after a 1-week placebo run-in period, blood pressure and the pulse rate were measured every 2 h except at night. TCV 116 monotherapy was started at 1 mg/day and increased stepwise at 3- to 5-day intervals to 2, 4 and 8 mg/day until a predetermined reduction in blood pressure was achieved. The daytime profiles of blood pressure and the pulse rate were again monitored at the end of the treatment period. In study 2, after a 4-week placebo run-in period, TCV 116 alone was administered for 2 weeks at 1 mg/day. The dose was then increased to 2 mg/day and stepwise at 2-week intervals to 4 and 8 mg/day until a predetermined reduction in blood pressure was achieved. The total treatment period was 8-12 weeks.


RESULTS
In study 1, a sufficient reduction in blood pressure was achieved in 19 of 28 patients (68%), with blood pressure significantly reduced at all measurement points, compared with the placebo run-in period. No differences were seen in the pulse rate. The only adverse reaction reported was a rash in one patient. In study 2, a sufficient reduction in blood pressure was achieved in 42 out of 55 patients (76%). The cumulative efficacy rate increased dose-dependently (15% at 1 mg/day, 38% at 2 mg/day, 60% at 4 mg/day and 76% at 8 mg/day). No differences were seen in the pulse rate. Adverse reactions were reported in three out of 55 patients (5.5%). No dry cough was reported by any of the patients.


CONCLUSIONS
TCV 116, an angiotensin II receptor antagonist, has potential as an antihypertensive agent. A dose of 4-8 mg once per day appears to be appropriate for the treatment of patients with mild to moderate essential hypertension.
Ogihara
T
T
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Arakawa
K
K
Iimura
O
O
Abe
K
K
Saruta
T
T
Ishii
M
M
Hiwada
K
K
Fujishima
M
M
Fukiyama
K
K
D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D004334:Drug Administration Schedule; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D012083:Renin / Q000097:blood; D013777:Tetrazoles
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D012083:Renin; C077793:candesartan cilexetil