Clinical Study to Evaluate the Antihypertensive Efficacy and Safety of Fimasartan in Hypertension Patients

• Sponsor: Boryung Pharmaceutical Co., Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00922480
• Collaborator: Seoul National University Hospital (Other), The Catholic University of Korea (Other), Kangbuk Samsung Hospital (Other), Konkuk University Medical Center (Other), Konyang University Hospital (Other), Keimyung University (Other), Korea University (Other), Korea University Guro Hospital (Other), Dongguk University International Hospital (Other), Seoul National University Bundang Hospital (Other), Samsung Medical Center (Other), Asan Medical Center (Other), Severance Hospital (Other), Ajou University (Other), Wonju Severance Christian Hospital (Other), Yeungnam University Hospital (Other), Yonsei University (Other), Inha University Hospital (Other), Chonbuk National University Hospital (Other), Cheil General Hospital and Women's Healthcare Center (Other), Chungnam National University (Other), Chungbuk National University Hospital (Other), Hanyang University (Other)
• Enrollment: 506
• Arms: 2
• Duration (Months): 9

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the antihypertensive efficacy and safety of Fimasartan (BR-A-657•K) 60 mg~120 mg in patients with mild to moderate essential hypertension.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Fimasartan; Drug: Losartan (Control)	Phase 3

Detailed Description

Fimasartan (BR-A-657-K), a selective blocker of AT1 receptor subtype, showed the rapid and potent antihypertensive effect in many hypertensive models. Phase I study, Fimasartan (BR-A-657-K) 20mg ~ 480mg single dosing with healthy subjects, demonstrated that the Fimasartan(BR-A-657-K) was very safe and well tolerated. Another phase I study, Fimasartan (BR-A-657-K) 120mg and 360mg dosing for 7 days, also showed that Fimasartan (BR-A-657-K) was safe and tolerable though one temporal adverse event was observed in high dose.

A Randomized, Double-blind, Losartan-controlled, Parallel Group Comparison Dose Titration Clinical Study to Evaluate the Antihypertensive Efficacy and Safety of Fimasartan (BR-A-657•K) 60mg~120mg in Patients with Mild to Moderate Essential Hypertension.

Approximately 480 patients will be enrolled over 12 months in 24 centers nationwide.

After 2 weeks of placebo run-in period, all subjects will be randomized into one of the following 2 groups. Subjects will take test/control drug for 12 weeks of treatment period. And Extensin study have 12 weeks in treatment period.

If subjects take any antihypertensive medications before screening, the subjects will have 1 week of wash-out period.

If the hypertension is not controlled well, there is a possibility of dose titration.

Group I : Fimasartan group. Group II : Losartan group

Study Design

• Study Type: Interventional
• Actual Enrollment: 506 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Losartan-controlled, Parallel Group Comparison Dose Titration Clinical Study to Evaluate the Antihypertensive Efficacy and Safety of Fimasartan 60mg~120mg in Patients With Mild to Moderate Essential Hypertension
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 2 Losartan group	Drug: Losartan (Control); Losartan 50 mg ~ 100 mg/po, take one tablets once a day; Other Names: Cozar
Active Comparator: 1 Fimasartan 60mg, 120mg	Drug: Fimasartan; Fimasartan 60 ~ 120mg/po take one tablets once a day; Other Names: A657-BR-CT

Outcome Measures

Primary Outcome Measures

1. Diastolic Blood Pressure Change [baseline and 12 weeks]

   Value of DBP at 12 Weeks minus value of DBP at Baseline while in a sitting position

Secondary Outcome Measures

1. Diastolic Blood Pressure Change [baseline and 4 weeks, 8 weeks]

   Value of DBP at 4 Weeks minus value of DBP at Baseline while in a sitting position Value of DBP at 8 Weeks minus value of DBP at Baseline while in a sitting position

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Mild to moderate essential hypertension : sitting diastolic blood pressure measured at Placebo visit and Baseline are 90~109mmHg inclusive and the difference between sitting diastolic blood pressures measured at Placebo visit and Baseline(Day0) is under 7mmHg.

• Subjects who agree to participate in this sudy and give written informed consent

• Subjects considered to understand the study, be cooperative, and able to be followed-up until the end of the study

Exclusion Criteria:

• The sitting DBP is less than 89mmHg or more than 110mmHg or severe hypertensive patient with sitting systolic blood pressure over 200mmHg Patients with secondary hypertension

• Patients with severe renal(Creatinine more 1.5 times than upper limit of normal), gastrointestinal, hematological or hepatic(AST, ALT more 2 twice more than upper limit of normal)disease etc. which might affect absorption, disposition, metabolism or excretion of the drug

• Patients with postural hypotension

• Patients with sever insulin dependent diabetes mellitus or uncontrolled diabetes mellitus(HbA1c>9%, regimen change of oral hypoglycemic agents within 12weeks, treated insulin before screening)

• Patients with a history of myocardial infarction, severe coronary artery disease or clinically significant heart failure or valvular defect in last 6 months

• Patients with consumptive disease, autoimmune disease, connective tissue disease

• Patients with a history of type B or C hepatitis(include carrier)

• Patients with HIV or hepatitis

• Patients with clinically significant laboratory abnormality

• Patients receiving any drugs known to affect blood pressure or medical treatments that can influence the blood pressure

• Patients with allergy or contraindication to any angiotensin II receptor antagonists

• Female of childbearing potential who does not undergo hysterectomy or is not post-menopausal

• Patients judged to have a history of alcohol or drug abuse by the investigator

• Patients participated other clinical trial 12 weeks before Screening Patients judged to be inappropriate for this study by the investigator with other reasons

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Boryung Pharmaceutical Co., Ltd
• Seoul National University Hospital
• The Catholic University of Korea
• Kangbuk Samsung Hospital
• Konkuk University Medical Center
• Konyang University Hospital
• Keimyung University
• Korea University
• Korea University Guro Hospital
• Dongguk University International Hospital
• Seoul National University Bundang Hospital
• Samsung Medical Center
• Asan Medical Center
• Severance Hospital
• Ajou University
• Wonju Severance Christian Hospital
• Yeungnam University Hospital
• Yonsei University
• Inha University Hospital
• Chonbuk National University Hospital
• Cheil General Hospital and Women's Healthcare Center
• Chungnam National University
• Chungbuk National University Hospital
• Hanyang University

Investigators

• Principal Investigator: Byung-Hee Oh, MD, Seoul National University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Boryung Pharmaceutical Co., Ltd
• ClinicalTrials.gov Identifier: NCT00922480
• Other Study ID Numbers: A657-BR-CT-301
• First Posted: Jun 17, 2009
• Last Update Posted: Apr 10, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by Boryung Pharmaceutical Co., Ltd: Hypertension; Losartan
• Additional relevant MeSH terms: Hypertension; Losartan

Study Results

Participant Flow

Arm/Group Title	Control: Losartan	Test: Fimasartan
Arm/Group Description	Losartan group Losartan (Control): Losartan 50 mg ~ 100 mg/po, take one tablets once a day	Fimasartan 60mg, 120mg Fimasartan: Fimasartan 60 ~ 120mg/po take one tablets once a day
Period Title: Main Study
STARTED	250	255
COMPLETED	213	226
NOT COMPLETED	37	29
Period Title: Main Study
STARTED	73	85
COMPLETED	68	82
NOT COMPLETED	5	3

Baseline Characteristics

Arm/Group Title	Control: Losartan	Test: Fimasartan	Total
Arm/Group Description	Losartan group Losartan (Control): Losartan 50 mg ~ 100 mg/po, take one tablets once a day	Fimasartan 60mg, 120mg Fimasartan: Fimasartan 60 ~ 120mg/po take one tablets once a day	Total of all reporting groups
Overall Participants	238	247	485
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.58 (9.61)	53.96 (8.79)	53.77 (9.19)
Sex: Female, Male (Count of Participants)
Female	71 29.8%	79 32%	150 30.9%
Male	167 70.2%	168 68%	335 69.1%

Outcome Measures

1. Primary Outcome

Title	Diastolic Blood Pressure Change
Description	Value of DBP at 12 Weeks minus value of DBP at Baseline while in a sitting position
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

As ITT group, these are subjects who have been randomly assigned and have at least one primary end point.

Arm/Group Title	Control: Losartan / Week 12 -ITT	Test: Fimasartan / Week 12 -ITT
Arm/Group Description	Losartan group Losartan (Control): Losartan 50 mg ~ 100 mg/po, take one tablets once a day	Fimasartan 60mg, 120mg Fimasartan: Fimasartan 60 ~ 120mg/po take one tablets once a day
Measure Participants	238	247
Mean (Standard Deviation) [mmHg]	-8.56 (7.72)	-11.26 (7.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control: Losartan / Week 12 -ITT, Test: Fimasartan / Week 12 -ITT
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-Inferiority
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test

2. Secondary Outcome

Title	Diastolic Blood Pressure Change
Description	Value of DBP at 4 Weeks minus value of DBP at Baseline while in a sitting position Value of DBP at 8 Weeks minus value of DBP at Baseline while in a sitting position
Time Frame	baseline and 4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

As ITT group, these are subjects who have been randomly assigned and have at least one primary end point.

Arm/Group Title	Control: Losartan / Week 4,8 -ITT	Test: Fimasartan / Week 4,8 -ITT
Arm/Group Description	Losartan group Losartan (Control): Losartan 50 mg ~ 100 mg/po, take one tablets once a day	Fimasartan 60mg, 120mg Fimasartan: Fimasartan 60 ~ 120mg/po take one tablets once a day
Measure Participants	238	247
Week 4	-5.73 (6.56)	-8.22 (7.35)
Week 8	-8.01 (7.16)	-11.01 (7.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control: Losartan / Week 12 -ITT, Test: Fimasartan / Week 12 -ITT
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-Inferiority
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test

Adverse Events

Arm/Group Title	Control: Losartan		Test: Fimasartan
Arm/Group Description	Losartan group Losartan (Control): Losartan 50 mg ~ 100 mg/po, take one tablets once a day		Fimasartan 60mg, 120mg Fimasartan: Fimasartan 60 ~ 120mg/po take one tablets once a day
All Cause Mortality
	Control: Losartan		Test: Fimasartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Control: Losartan		Test: Fimasartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/250 (2%)		3/255 (1.2%)
Cardiac disorders
coronary artery occlusion	1/250 (0.4%)	1	0/255 (0%)	0
Infections and infestations
Appendicitis	0/250 (0%)	0	1/255 (0.4%)	1
Pneumonia	1/250 (0.4%)	1	0/255 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	1/250 (0.4%)	1	0/255 (0%)	0
Multiple fracture	0/250 (0%)	0	1/255 (0.4%)	1
Road traffic accident	1/250 (0.4%)	1	0/255 (0%)	0
Spinal compression fracture	0/250 (0%)	0	1/255 (0.4%)	1
Musculoskeletal and connective tissue disorders
Osteonecrosis	1/250 (0.4%)	1	0/255 (0%)	0
Other (Not Including Serious) Adverse Events
	Control: Losartan		Test: Fimasartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/250 (30.4%)		82/255 (32.2%)
Cardiac disorders
Palpitations	2/250 (0.8%)	2	3/255 (1.2%)	3
Tachycardia	2/250 (0.8%)	2	0/255 (0%)	0
Supraventricular extrasystoles	0/250 (0%)	0	1/255 (0.4%)	1
Ear and labyrinth disorders
Eustachian tube dysfunction	1/250 (0.4%)	1	0/255 (0%)	0
Vertigo	0/250 (0%)	0	1/255 (0.4%)	1
Eye disorders
Blepharospasm	1/250 (0.4%)	1	0/255 (0%)	0
Conjunctivitis allergic	0/250 (0%)	0	1/255 (0.4%)	1
Eye pruritus	0/250 (0%)	0	1/255 (0.4%)	1
Eyelid ptosis	1/250 (0.4%)	1	0/255 (0%)	0
Keratoconjunctivitis sicca	1/250 (0.4%)	1	0/255 (0%)	0
Ocular hyperaemia	0/250 (0%)	0	1/255 (0.4%)	1
Xerophthalmia	0/250 (0%)	0	1/255 (0.4%)	1
Gastrointestinal disorders
Dyspepsia	5/250 (2%)	5	2/255 (0.8%)	2
Nausea	4/250 (1.6%)	4	2/255 (0.8%)	2
Constipation	1/250 (0.4%)	1	3/255 (1.2%)	3
Gastritis	4/250 (1.6%)	4	0/255 (0%)	0
Vomiting	1/250 (0.4%)	1	1/255 (0.4%)	1
Abdominal discomfort	1/250 (0.4%)	1	0/255 (0%)	0
Abdominal distension	0/250 (0%)	0	1/255 (0.4%)	1
Abdominal pain upper	1/250 (0.4%)	1	0/255 (0%)	0
Dental caries	1/250 (0.4%)	1	0/255 (0%)	0
Dry mouth	0/250 (0%)	0	1/255 (0.4%)	1
Flatulence	0/250 (0%)	0	1/255 (0.4%)	1
Gastric ulcer	0/250 (0%)	0	1/255 (0.4%)	1
Gastritis erosive	0/250 (0%)	0	1/255 (0.4%)	1
Gastrointestinal disorder	0/250 (0%)	0	1/255 (0.4%)	1
Gastrooesophageal reflux disease	1/250 (0.4%)	1	0/255 (0%)	0
Palatal oedema	0/250 (0%)	0	1/255 (0.4%)	1
Tongue discolouration	1/250 (0.4%)	1	0/255 (0%)	0
General disorders
Chest discomfort	3/250 (1.2%)	3	3/255 (1.2%)	3
Chest pain	2/250 (0.8%)	2	2/255 (0.8%)	2
Asthenia	0/250 (0%)	0	2/255 (0.8%)	2
Face oedema	1/250 (0.4%)	1	0/255 (0%)	0
Fatigue	0/250 (0%)	0	1/255 (0.4%)	1
Hepatobiliary disorders
Cholelithiasis	1/250 (0.4%)	1	0/255 (0%)	0
Hepatitis alcoholic	0/250 (0%)	0	1/255 (0.4%)	1
Infections and infestations
Nasopharyngitis	5/250 (2%)	6	8/255 (3.1%)	8
Upper respiratory tract infection	3/250 (1.2%)	3	5/255 (2%)	5
Rhinitis	3/250 (1.2%)	3	0/255 (0%)	0
Bronchitis	1/250 (0.4%)	1	0/255 (0%)	0
Cystitis	1/250 (0.4%)	1	0/255 (0%)	0
Herpes zoster	1/250 (0.4%)	1	0/255 (0%)	0
Otitis media	1/250 (0.4%)	1	0/255 (0%)	0
Otitis media acute	0/250 (0%)	0	1/255 (0.4%)	1
pharyngitis	1/250 (0.4%)	1	1/255 (0.4%)	1
Injury, poisoning and procedural complications
Foot fracture	0/250 (0%)	0	1/255 (0.4%)	1
Radius fracture	0/250 (0%)	0	1/255 (0.4%)	1
Wrist fracture	0/250 (0%)	0	1/255 (0.4%)	1
Investigations
Alanine aminotransferase increased	1/250 (0.4%)	1	4/255 (1.6%)	4
Aspartate aminotransferase increased	1/250 (0.4%)	1	4/255 (1.6%)	4
Blood urine present	0/250 (0%)	0	2/255 (0.8%)	2
Glucose urine present	2/250 (0.8%)	2	0/255 (0%)	0
Blood alkaline phosphatase increased	0/250 (0%)	0	1/255 (0.4%)	1
Blood bilirubin increased	0/250 (0%)	0	1/255 (0.4%)	1
Low density lipoprotein increased	0/250 (0%)	0	1/255 (0.4%)	1
Platelet count decreased	0/250 (0%)	0	1/255 (0.4%)	1
Spinal X-ray abnormal	0/250 (0%)	0	1/255 (0.4%)	1
Metabolism and nutrition disorders
Hypercholesterolaemia	2/250 (0.8%)	2	1/255 (0.4%)	1
Hyperlipidaemia	0/250 (0%)	0	2/255 (0.8%)	2
Anorexia	1/250 (0.4%)	1	0/255 (0%)	0
Gout	0/250 (0%)	0	1/255 (0.4%)	1
Hyperkalaemia	1/250 (0.4%)	1	0/255 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	2/250 (0.8%)	2	2/255 (0.8%)	2
Arthralgia	0/250 (0%)	0	2/255 (0.8%)	2
Pain in extremity	0/250 (0%)	0	2/255 (0.8%)	2
Arthritis	0/250 (0%)	0	1/255 (0.4%)	1
Intervertebral disc protrusion	1/250 (0.4%)	1	0/255 (0%)	0
Joint effusion	0/250 (0%)	0	1/255 (0.4%)	1
Muscle twitching	0/250 (0%)	0	1/255 (0.4%)	1
Muscular weakness	1/250 (0.4%)	1	0/255 (0%)	0
Musculoskeletal discomfort	0/250 (0%)	0	1/255 (0.4%)	1
Musculoskeletal pain	0/250 (0%)	0	1/255 (0.4%)	1
Neck pain	0/250 (0%)	0	1/255 (0.4%)	1
Pelvic deformity	0/250 (0%)	0	1/255 (0.4%)	1
Spinal osteoarthritis	0/250 (0%)	0	1/255 (0.4%)	1
Tendonitis	0/250 (0%)	0	1/255 (0.4%)	1
Nervous system disorders
Headache	17/250 (6.8%)	18	16/255 (6.3%)	17
Dizziness	9/250 (3.6%)	10	11/255 (4.3%)	11
Hypoaesthesia	2/250 (0.8%)	2	0/255 (0%)	0
Migraine	0/250 (0%)	0	2/255 (0.8%)	2
Dysaesthesia	1/250 (0.4%)	1	0/255 (0%)	0
Dysarthria	1/250 (0.4%)	1	0/255 (0%)	0
Global amnesia	0/250 (0%)	0	1/255 (0.4%)	1
Paraesthesia	1/250 (0.4%)	1	0/255 (0%)	0
Somnolence	1/250 (0.4%)	1	0/255 (0%)	0
Syncope	0/250 (0%)	0	1/255 (0.4%)	1
Psychiatric disorders
Anxiety	1/250 (0.4%)	1	1/255 (0.4%)	1
Depression	0/250 (0%)	0	1/255 (0.4%)	1
insomnia	1/250 (0.4%)	1	0/255 (0%)	0
Renal and urinary disorders
Pollakiuria	1/250 (0.4%)	1	0/255 (0%)	0
Renal cyst	0/250 (0%)	0	1/255 (0.4%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/250 (0.4%)	1	0/255 (0%)	0
Erectile dysfunction	0/250 (0%)	0	1/255 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/250 (0%)	0	3/255 (1.2%)	3
Rhinorrhoea	0/250 (0%)	0	2/255 (0.8%)	2
Dyspnoea	1/250 (0.4%)	1	0/255 (0%)	0
Dyspnoea exertional	1/250 (0.4%)	1	0/255 (0%)	0
Epistaxis	1/250 (0.4%)	1	0/255 (0%)	0
Nasal discomfort	1/250 (0.4%)	1	0/255 (0%)	0
Rhinitis allergic	1/250 (0.4%)	1	0/255 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	3/250 (1.2%)	3	4/255 (1.6%)	4
Urticaria	1/250 (0.4%)	1	1/255 (0.4%)	1
Urticaria localised	0/250 (0%)	0	2/255 (0.8%)	2
Rash	1/250 (0.4%)	1	0/255 (0%)	0
Vascular disorders
Flushing	2/250 (0.8%)	2	1/255 (0.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.