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

June 4, 2015 updated by: Stendhal Americas, S.A.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

272

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
      • San Luis Potosí, Mexico, 78240
        • Hospital Dr. Ignacio Morones Prieto
    • Baja California
      • Tijuana, Baja California, Mexico, 22010
        • Centro Médico Exel
    • D.f.
      • Mexico, D.f., Mexico, 06090
        • Hospital de Jesús IAP
      • Mexico, D.f., Mexico, 07330
        • Hospital General de Ticomán
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44100
        • Hospital Civil de Guadalajara Fray Antonio Alcalde
      • Guadalajara, Jalisco, Mexico, 44140
        • Unidad de Investigacion Clinica Cardiometabolica de Occidente
      • Guadalajara, Jalisco, Mexico, 44340
        • Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara
      • Guadalajara, Jalisco, Mexico, 44600
        • Icle S.C.
      • Guadalajara, Jalisco, Mexico, 44860
        • Nucleo Medico la Paz
      • Zapopan, Jalisco, Mexico, 45157
        • Hospital Dr. Ángel Leaño
    • Jalsico
      • Guadalajara, Jalsico, Mexico, 44600
        • Instituto Jalisciense de Investigación en Diabetes y Obesidad S. C.
    • Nuevo León
      • Monterrey, Nuevo León, Mexico, 64060
        • Cardiolink Clintrials
      • Monterrey, Nuevo León, Mexico, 64620
        • Centro de Estudios Clínicos y Especialidades Médicas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fimasartan 60 mg Tablets
FMS 60 mg tablets once a day during the initial 8 treatment weeks of the study
Drug: Fimasartan
Fimasartan tablets
Other Names:
  • Arakhor
  • Kanarb
Active Comparator: Fimasartan 120 mg Tablets
FMS 120 mg tablets once a day during 4 weeks (treatment weeks 8 to 12)
Drug: Fimasartan
Fimasartan tablets
Other Names:
  • Arakhor
  • Kanarb
Active Comparator: Fimasartan; Hydrochlorothiazide 60/12.5
FMS 60 mg + HCTZ 12.5 mg tablets (fixed dose combination) once a day during 4 weeks (treatment weeks 8 to 12)
Drug: Fimasartan; Hydrochlorothiazide
Fimasartan plus hydrochlorothiazide fixed dose combination tablets
Other Names:
  • Diarakhor
  • Kanarb plus
Experimental: Fimasartan; Hydrochlorothiazide 120/12.5
FMS 120 mg + HCTZ 12.5 mg tablets (fixed dose combination) once a day during 12 weeks (treatment weeks 12 to 24)
Drug: Fimasartan; Hydrochlorothiazide
Fimasartan plus hydrochlorothiazide fixed dose combination tablets
Other Names:
  • Diarakhor
  • Kanarb plus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Pressure Change From Baseline
Time Frame: Baseline to Treatment Week 8
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Pressure Change from Week 8
Time Frame: Treatment Week 8 to Treatment Week 12
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
Week 8 Treatment Response Rate
Time Frame: Baseline to Treatment Week 8
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
Week 12 Treatment Response Rate
Time Frame: Treatment Weeks 8 to 12
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
Blood Pressure Change from Week 12
Time Frame: Treatment Weeks 12 to 24
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
Week 24 Treatment Response Rate
Time Frame: Treatment Weeks 12 to 24
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
Adverse Event Incidence
Time Frame: Baseline to Treatment Week 24
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pro-inflammatory marker changes from baseline
Time Frame: Baseline to treatment week 8
Treatment Week 8 mean changes from baseline serum concentrations of hsCRP, adiponectin, ICAM-1 and IL6
Baseline to treatment week 8
Treatment Week 8 ABPM mean 24-hour BP changes from baseline
Time Frame: Baseline to treatment week 8
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
Treatment Week 8 ABPM mean Daytime BP changes from baseline
Time Frame: Baseline to treatment week 8
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
Treatment Week 8 ABPM mean Nighttime BP changes from baseline
Time Frame: Baseline to treatment week 8
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stendhal Americas, S.A.

Investigators

  • Study Chair: Ignacio Conde-Carmona, M.D., Específicos Stendhal S.A. de C.V.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

June 3, 2015

First Submitted That Met QC Criteria

June 4, 2015

First Posted (Estimate)

June 9, 2015

Study Record Updates

Last Update Posted (Estimate)

June 9, 2015

Last Update Submitted That Met QC Criteria

June 4, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FIMA-MEX-12-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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