Efficacy and Safety of Fimasartan Alone or Combined With HCTZ in Mexican Patients With Essential Hypertension

Hypertension, Essential Clinical Trial

— FIRME-1  

Official title:

A 24-week Trial of the Effectiveness and Safety of Fimasartan 60 mg Alone as Initial Treatment and Its Randomized Escalation to Fimasartan 120 mg or Fimasartan 60 mg/HCTZ 12.5 mg in Mexican Patients With Grade 1 and 2 Essential Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02466490
• Other study ID #: FIMA-MEX-12-01
• Status: Completed
• Phase: Phase 3
• First received: June 3, 2015
• Last updated: June 4, 2015
• Start date: April 2013
• Est. completion date: February 2014

Study information

• Verified date: June 2015
• Source: Stendhal Americas, S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Mexico: Federal Commission for Protection Against Health Risks
• Study type: Interventional

Clinical Trial Summary

Fimasartan (FMS) is an AT1 receptor antagonist indicated for once a day administration, currently approved for the treatment of essential hypertension in Corea and Mexico. As the safety and efficacy of FMS was initially demonstrated in Korea only, it was necessary to address the potential for ethnic factors to have an effect on the drug´s efficacy and safety in the Mexican population. To address this need, a cohort of 272 Mexican subjects with grades 1-2 essential hypertension were sequentially treated on a treat to target basis (target: sitting Diastolic Blood Pressure (sDBP) <90 mmHg) with 60 mg FMS once a day (8 weeks), either 120 mg FMS or 60 mg FMS+12.5 mg HCTZ once a day (randomized 4 week treatment period) and 120 mg FMS once a day (during 12 weeks) for a total treatment period of 24 weeks.

Description:

This was a prospective, open, multicentre, 24 week study of subjects with grade 1-2 essential hypertension eligible, according to the participating investigator's clinical judgement, to initial monotherapy.

Consenting, eligible subjects at 13 Mexican participating centers were initially assigned to monotherapy with 60 mg FMS once a day. At treatment week 8, those subjects with a sDBP ≥90 mmHg were randomized to either 120 mg FMS or to 60 mg FMS + 12.5 mg hydrochlorothiazide (HCTZ) once a day during 4 weeks. At treatment week 12, all non-responding subjects were finally assigned to 120 mg FMS + 12.5 mg HCTZ for the remaining 12 weeks of the planned 24 week treatment period. At treatment weeks 8 and 12, those subjects with a sDBP < 90 mmHg remained on their assigned treatment for the rest of the study.

This cohort study was designed to collect information on treatment effect (blood pressure changes from baseline/reference time and treatment response rates), and safety (i.e., incidence and characterization of clinical, laboratory and ECG adverse events); accordingly, subjects were assessed at treatment weeks 4, 8, 12, 16, 20 and 24 in terms of vital signs, clinical laboratory safety parameters, concomitant medications and adverse events. 12-lead ECG recordings were obtained from all subjects both at screening and at treatment week 24 and a subset of 11 subjects underwent both baseline and treatment week 8 24-hour ABPM recordings.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 272
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Ability to understand the study subject information and to voluntarily grant their informed consent.

• Men or women, 18 to 70 years old.

• With grade 1 or 2 essential arterial hypertension based on a sitting diastolic blood pressure (DBP) =90 mmHg and =109 mmHg (MEXICAN OFFICIAL NORM 030-SSA).

• Trustworthiness and willingness to attend all the study follow-up visits , according to the investigator's judgment.

• Patients already on antihypertensive therapy, not adequately controlled and that, according to the investigator's judgment, could be safely submitted to a two-week washout period.

Exclusion Criteria:

• Severe hypertension (Grade 3), with SBP=180 mmHg and/or DBP=110 mmHg, according to OFFICIAL MEXICAN NORM NOM 030-SSA criteria.

• Secondary hypertension.

• Impossibility to safely undergo a two week washout period from previous treatment prior to assignment to the study treatment, if applicable and according to the principal investigator´s judgment.

• Systemic diseases such as renal dysfunction (creatinine =1.5 time above the upper limit of the reference range), gastrointestinal disorders, hematological disorders or liver dysfunction (AST y/o ALT =1.5 times the upper limit of the reference range), capable to affect the absorption, distribution, metabolism and excretion of the study drug.

• Non-controlled diabetes mellitus (HbA1c>9%)

• Morbid obesity (BMI=40 kg/m2)

• Myocardial infarction or severe coronary artery disease or clinically significant congestive heart failure, within the six months prior to the screening visit.

• Auto-immune or connective tissue disease.

• Evidence in the medical record of serious infectious diseases such as hepatitis type B or C or a positive HIV test at screening.

• Clinically significant laboratory test abnormalities, according to the investigator's judgment.

• Concomitant treatment which might affect blood pressure values.

• Known allergies or contraindication to the use of angiotensin II receptor antagonists.

• Pregnancy, breastfeeding or in the case of women with childbearing potential, the rejection to use an effective contraceptive method, according to the investigator's judgment.

• History of alcohol or addictive substance abuse.

• Subjects participating in other clinical studies or who have participated in other study within the 6 months prior to screening.

• Any other reason which in the investigator's opinion might contraindicate the participation of a subject in the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Essential

Intervention

Drug:
• Fimasartan
Fimasartan tablets
• Fimasartan; Hydrochlorothiazide
Fimasartan plus hydrochlorothiazide fixed dose combination tablets

Locations

Country	Name	City	State
Mexico	Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara	Guadalajara	Jalisco
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara	Jalisco
Mexico	Icle S.C.	Guadalajara	Jalisco
Mexico	Instituto Jalisciense de Investigación en Diabetes y Obesidad S. C.	Guadalajara	Jalsico
Mexico	Núcleo Médico La Paz	Guadalajara	Jalisco
Mexico	Unidad de Investigación Clínica Cardiometabólica de Occidente	Guadalajara	Jalisco
Mexico	Hospital de Jesús IAP	Mexico	D.f.
Mexico	Hospital General de Ticomán	Mexico	D.f.
Mexico	Cardiolink Clintrials	Monterrey	Nuevo León
Mexico	Centro de Estudios Clínicos y Especialidades Médicas	Monterrey	Nuevo León
Mexico	Hospital Dr. Ignacio Morones Prieto	San Luis Potosí
Mexico	Centro Médico Exel	Tijuana	Baja California
Mexico	Hospital Dr. Ángel Leaño	Zapopan	Jalisco

Sponsors (1)

Lead Sponsor	Collaborator
Stendhal Americas, S.A.

Country where clinical trial is conducted

Mexico, 

References & Publications (6)

Chi YH, Lee H, Paik SH, Lee JH, Yoo BW, Kim JH, Tan HK, Kim SL. Safety, tolerability, pharmacokinetics, and pharmacodynamics of fimasartan following single and repeated oral administration in the fasted and fed states in healthy subjects. Am J Cardiovasc — View Citation

Lee H, Kim KS, Chae SC, Jeong MH, Kim DS, Oh BH. Ambulatory blood pressure response to once-daily fimasartan: an 8-week, multicenter, randomized, double-blind, active-comparator, parallel-group study in Korean patients with mild to moderate essential hype — View Citation

Lee H, Yang HM, Lee HY, Kim JJ, Choi DJ, Seung KB, Jeon ES, Ha JW, Rim SJ, Park JB, Shin JH, Oh BH. Efficacy and tolerability of once-daily oral fimasartan 20 to 240 mg/d in Korean Patients with hypertension: findings from Two Phase II, randomized, double — View Citation

Lee SE, Kim YJ, Lee HY, Yang HM, Park CG, Kim JJ, Kim SK, Rhee MY, Oh BH; Investigators. Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, rando — View Citation

Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):29-38. Epub 2004 Nov 11. Review. — View Citation

Park JB, Sung KC, Kang SM, Cho EJ. Safety and efficacy of fimasartan in patients with arterial hypertension (Safe-KanArb study): an open-label observational study. Am J Cardiovasc Drugs. 2013 Feb;13(1):47-56. doi: 10.1007/s40256-013-0004-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pro-inflammatory marker changes from baseline	Treatment Week 8 mean changes from baseline serum concentrations of hsCRP, adiponectin, ICAM-1 and IL6	Baseline to treatment week 8	No
Other	Treatment Week 8 ABPM mean 24-hour BP changes from baseline	Treatment week 8 mean 24-hour sDBP and sSBO changes from baseline in a subset of subjects with valid baseline and treatment week 8 ABPM recordings at two selected sites	Baseline to treatment week 8	No
Other	Treatment Week 8 ABPM mean Daytime BP changes from baseline	Treatment week 8 mean Daytime sDBP and sSBO changes from baseline in a subset of subjects with valid baseline and treatment week 8 ABPM recordings at two selected sites	Baseline to treatment week 8	No
Other	Treatment Week 8 ABPM mean Nighttime BP changes from baseline	Treatment week 8 mean Nighttime sDBP and sSBO changes from baseline in a subset of subjects with valid baseline and treatment week 8 ABPM recordings at two selected sites	Baseline to treatment week 8	No
Primary	Blood Pressure Change From Baseline	Treatment Week 8 mean sDBP and sitting Systolic Blood Pressure (SBP) changes from baseline (all study subjects treated with 60 mg FMS once a day)	Baseline to Treatment Week 8	No
Secondary	Blood Pressure Change from Week 8	Treatment Week 12 mean sDBP and sSBP changes from week 8 on subjects randomized to either 120 mg FMS or 60 mg FMS + 12.5 mg HCTZ once a day	Treatment Week 8 to Treatment Week 12	No
Secondary	Week 8 Treatment Response Rate	Proportion of subjects with sDBP < 90 mmHg at treatment week 8 (all subjects treated with 60 mg FMS once a day)	Baseline to Treatment Week 8	No
Secondary	Week 12 Treatment Response Rate	Proportion of subjects with sDBP < 90 mmHg at treatment week 12 (subjects randomized to either 120 mg FMS or 60 mg FMS + 12.5 mg HCTZ once a day)	Treatment Weeks 8 to 12	No
Secondary	Blood Pressure Change from Week 12	Treatment Week 24 mean sDBP and sSBP changes from treatment week 12 (subjects assigned at treatment week 12 to 120 mg FMS + 12.5 mg HCTZ	Treatment Weeks 12 to 24	No
Secondary	Week 24 Treatment Response Rate	Proportion of non-responding subjects assigned at treatment week 12 to 120 mg FMS + 12.5 mg HCTZ with sDBP < 90 mmHg at Treatment Week 24	Treatment Weeks 12 to 24	No
Secondary	Adverse Event Incidence	Incidence and characterization of clinical, laboratory and ECG adverse events observed in all subjects assigned to treatment in the study receiving at least one dose of the study medications	Baseline to Treatment Week 24	No