Clinical trial NCT02466490: Efficacy and Safety of Fimasartan Alone or Combined With HCTZ in Mexican Patients With Essential Hypertension
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension, Essential
Lead sponsor: Stendhal Americas, S.A.
Sponsor class: INDUSTRY
First posted: 2015-06-09
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Blood Pressure Change From Baseline
timeFrame: Baseline to Treatment Week 8
Secondary outcomes:
measure: Blood Pressure Change from Week 8
timeFrame: Treatment Week 8 to Treatment Week 12
measure: Week 8 Treatment Response Rate
timeFrame: Baseline to Treatment Week 8
measure: Week 12 Treatment Response Rate
timeFrame: Treatment Weeks 8 to 12
measure: Blood Pressure Change from Week 12
timeFrame: Treatment Weeks 12 to 24
measure: Week 24 Treatment Response Rate
timeFrame: Treatment Weeks 12 to 24
measure: Adverse Event Incidence
timeFrame: Baseline to Treatment Week 24
Other outcomes:
measure: Pro-inflammatory marker changes from baseline
timeFrame: Baseline to treatment week 8
measure: Treatment Week 8 ABPM mean 24-hour BP changes from baseline
timeFrame: Baseline to treatment week 8
measure: Treatment Week 8 ABPM mean Daytime BP changes from baseline
timeFrame: Baseline to treatment week 8
measure: Treatment Week 8 ABPM mean Nighttime BP changes from baseline
timeFrame: Baseline to treatment week 8
Locations:
city: Tijuana
country: Mexico
facility: Centro Médico Exel
state: Baja California
city: Mexico
country: Mexico
facility: Hospital de Jesús IAP
state: D.f.
city: Mexico
country: Mexico
facility: Hospital General de Ticomán
state: D.f.
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Fray Antonio Alcalde
state: Jalisco
city: Guadalajara
country: Mexico
facility: Unidad de Investigación Clínica Cardiometabólica de Occidente
state: Jalisco
city: Guadalajara
country: Mexico
facility: Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara
state: Jalisco
city: Guadalajara
country: Mexico
facility: Icle S.C.
state: Jalisco
city: Guadalajara
country: Mexico
facility: Núcleo Médico La Paz
state: Jalisco
city: Zapopan
country: Mexico
facility: Hospital Dr. Ángel Leaño
state: Jalisco
city: Guadalajara
country: Mexico
facility: Instituto Jalisciense de Investigación en Diabetes y Obesidad S. C.
state: Jalsico
city: Monterrey
country: Mexico
facility: Cardiolink Clintrials
state: Nuevo León
city: Monterrey
country: Mexico
facility: Centro de Estudios Clínicos y Especialidades Médicas
state: Nuevo León
city: San Luis Potosí
country: Mexico
facility: Hospital Dr. Ignacio Morones Prieto
Study officials:
affiliation: Específicos Stendhal S.A. de C.V.
name: Ignacio Conde-Carmona, M.D.
role: STUDY_CHAIR
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