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Efficacy and Safety of Fimasartan Alone or Combined With HCTZ in Mexican Patients With Essential Hypertension (FIRME-1)

Primary Purpose

Hypertension, Essential

Status

Completed

Phase

Phase 3

Locations

Mexico

Study Type

Interventional

Intervention

Fimasartan

Fimasartan; Hydrochlorothiazide

About this trial

This is an interventional treatment trial for Hypertension, Essential

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Centro Médico Exel
Hospital de Jesús IAP
Hospital General de Ticomán
Hospital Civil de Guadalajara Fray Antonio Alcalde
Unidad de Investigación Clínica Cardiometabólica de Occidente
Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara
Icle S.C.
Núcleo Médico La Paz
Hospital Dr. Ángel Leaño
Instituto Jalisciense de Investigación en Diabetes y Obesidad S. C.
Cardiolink Clintrials
Centro de Estudios Clínicos y Especialidades Médicas
Hospital Dr. Ignacio Morones Prieto

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Fimasartan 60 mg Tablets

Fimasartan 120 mg Tablets

Fimasartan; Hydrochlorothiazide 60/12.5

Fimasartan; Hydrochlorothiazide 120/12.5

Arm Description

FMS 60 mg tablets once a day during the initial 8 treatment weeks of the study

FMS 120 mg tablets once a day during 4 weeks (treatment weeks 8 to 12)

FMS 60 mg + HCTZ 12.5 mg tablets (fixed dose combination) once a day during 4 weeks (treatment weeks 8 to 12)

FMS 120 mg + HCTZ 12.5 mg tablets (fixed dose combination) once a day during 12 weeks (treatment weeks 12 to 24)

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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

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)

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)

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

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

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

Full Information

NCT ID

NCT02466490

First Posted

June 3, 2015

Last Updated

June 4, 2015

Sponsor

Stendhal Americas, S.A.

1. Study Identification

Unique Protocol Identification Number

NCT02466490

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

April 2013 (undefined)

Primary Completion Date

February 2014 (Actual)

Study Completion Date

February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Stendhal Americas, S.A.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypertension, Essential

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

272 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fimasartan 60 mg Tablets

Arm Type

Experimental

Arm Description

FMS 60 mg tablets once a day during the initial 8 treatment weeks of the study

Arm Title

Fimasartan 120 mg Tablets

Arm Type

Active Comparator

Arm Description

FMS 120 mg tablets once a day during 4 weeks (treatment weeks 8 to 12)

Arm Title

Fimasartan; Hydrochlorothiazide 60/12.5

Arm Type

Active Comparator

Arm Description

FMS 60 mg + HCTZ 12.5 mg tablets (fixed dose combination) once a day during 4 weeks (treatment weeks 8 to 12)

Arm Title

Fimasartan; Hydrochlorothiazide 120/12.5

Arm Type

Experimental

Arm Description

FMS 120 mg + HCTZ 12.5 mg tablets (fixed dose combination) once a day during 12 weeks (treatment weeks 12 to 24)

Intervention Type

Drug

Intervention Name(s)

Fimasartan

Other Intervention Name(s)

Arakhor, Kanarb

Intervention Description

Fimasartan tablets

Intervention Type

Drug

Intervention Name(s)

Fimasartan; Hydrochlorothiazide

Other Intervention Name(s)

Diarakhor, Kanarb plus

Intervention Description

Fimasartan plus hydrochlorothiazide fixed dose combination tablets

Primary Outcome Measure Information:

Title

Blood Pressure Change From Baseline

Description

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)

Time Frame

Baseline to Treatment Week 8

Secondary Outcome Measure Information:

Title

Blood Pressure Change from Week 8

Description

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

Time Frame

Treatment Week 8 to Treatment Week 12

Title

Week 8 Treatment Response Rate

Description

Proportion of subjects with sDBP < 90 mmHg at treatment week 8 (all subjects treated with 60 mg FMS once a day)

Time Frame

Baseline to Treatment Week 8

Title

Week 12 Treatment Response Rate

Description

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)

Time Frame

Treatment Weeks 8 to 12

Title

Blood Pressure Change from Week 12

Description

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

Time Frame

Treatment Weeks 12 to 24

Title

Week 24 Treatment Response Rate

Description

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

Time Frame

Treatment Weeks 12 to 24

Title

Adverse Event Incidence

Description

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

Time Frame

Baseline to Treatment Week 24

Other Pre-specified Outcome Measures:

Title

Pro-inflammatory marker changes from baseline

Description

Treatment Week 8 mean changes from baseline serum concentrations of hsCRP, adiponectin, ICAM-1 and IL6

Time Frame

Baseline to treatment week 8

Title

Treatment Week 8 ABPM mean 24-hour BP changes from baseline

Description

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

Time Frame

Baseline to treatment week 8

Title

Treatment Week 8 ABPM mean Daytime BP changes from baseline

Description

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

Time Frame

Baseline to treatment week 8

Title

Treatment Week 8 ABPM mean Nighttime BP changes from baseline

Description

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

Time Frame

Baseline to treatment week 8

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ignacio Conde-Carmona, M.D.

Organizational Affiliation

Específicos Stendhal S.A. de C.V.

Official's Role

Study Chair

Facility Information:

Facility Name

Centro Médico Exel

City

Tijuana

State/Province

Baja California

ZIP/Postal Code

22010

Country

Mexico

Facility Name

Hospital de Jesús IAP

City

Mexico

State/Province

D.f.

ZIP/Postal Code

06090

Country

Mexico

Facility Name

Hospital General de Ticomán

City

Mexico

State/Province

D.f.

ZIP/Postal Code

07330

Country

Mexico

Facility Name

Hospital Civil de Guadalajara Fray Antonio Alcalde

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44100

Country

Mexico

Facility Name

Unidad de Investigación Clínica Cardiometabólica de Occidente

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44140

Country

Mexico

Facility Name

Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44340

Country

Mexico

Facility Name

Icle S.C.

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44600

Country

Mexico

Facility Name

Núcleo Médico La Paz

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44860

Country

Mexico

Facility Name

Hospital Dr. Ángel Leaño

City

Zapopan

State/Province

Jalisco

ZIP/Postal Code

45157

Country

Mexico

Facility Name

Instituto Jalisciense de Investigación en Diabetes y Obesidad S. C.

City

Guadalajara

State/Province

Jalsico

ZIP/Postal Code

44600

Country

Mexico

Facility Name

Cardiolink Clintrials

City

Monterrey

State/Province

Nuevo León

ZIP/Postal Code

64060

Country

Mexico

Facility Name

Centro de Estudios Clínicos y Especialidades Médicas

City

Monterrey

State/Province

Nuevo León

ZIP/Postal Code

64620

Country

Mexico

Facility Name

Hospital Dr. Ignacio Morones Prieto

City

San Luis Potosí

ZIP/Postal Code

78240

Country

Mexico

12. IPD Sharing Statement

Citations:

PubMed Identifier

22608107

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-blind, placebo-controlled studies. Clin Ther. 2012 Jun;34(6):1273-89. doi: 10.1016/j.clinthera.2012.04.021. Epub 2012 May 17. Erratum In: Clin Ther. 2012 Sep;34(9):2020.

Results Reference

result

PubMed Identifier

22381711

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, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-week extension phase in adult Korean patients with mild-to-moderate hypertension. Clin Ther. 2012 Mar;34(3):552-568, 568.e1-9. doi: 10.1016/j.clinthera.2012.01.024. Epub 2012 Mar 3.

Results Reference

result

PubMed Identifier

23932463

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 hypertension. Clin Ther. 2013 Sep;35(9):1337-49. doi: 10.1016/j.clinthera.2013.06.021. Epub 2013 Aug 7.

Results Reference

result

PubMed Identifier

23344912

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.

Results Reference

result

PubMed Identifier

21910510

Citation

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 Drugs. 2011 Oct 1;11(5):335-46. doi: 10.2165/11593840-000000000-00000.

Results Reference

result

PubMed Identifier

15539615

Citation

Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):29-38. doi: 10.1161/01.ATV.0000150649.39934.13. Epub 2004 Nov 11.

Results Reference

result

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

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