Efficacy and Safety Evaluating Study to Compare Kanarb (Fimasartan) and Cozaar® (Losartan) in Adult Patients With Grade I-II Arterial Hypertension

• Sponsor: R-Pharm (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02248961
• Collaborator: Covance (Industry), Boryung Pharmaceutical Co., Ltd (Industry)
• Enrollment: 179
• Locations: 13
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 13.8
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Assess and compare the efficacy and safety of Kanarb (Fimasartan), manufactured by Boryung Pharmaceutical Co., Ltd, Republic of Korea, tablets 60/120 mg and Cozaar® (Losartan), manufactured by MERCK SHARP & DOHME B.V., Netherlands, tablet 50/100 mg in adult patients with Grade I-II arterial hypertension in 12 weeks of therapy

Condition or Disease	Intervention/Treatment	Phase
Arterial Hypertension	Drug: Fimasartan; Drug: Losartan	Phase 3

Detailed Description

1. To evaluate efficacy of 12-week Kanarb (Fimasartan), manufactured by Boryung Pharmaceutical Co., Ltd, Republic of Korea, tablets 60/120 mg and Cozaar® (Losartan), manufactured by MERCK SHARP & DOHME B.V., Netherlands, tablet 50/100 mg in adult patients with Grade I-II arterial hypertension.

2. To evaluate safety of 12-week Kanarb (Fimasartan), manufactured by Boryung Pharmaceutical Co., Ltd, Republic of Korea, tablets 60/120 mg and Cozaar® (Losartan), manufactured by MERCK SHARP & DOHME B.V., Netherlands, tablet 50/100 mg in adult patients with Grade I-II arterial hypertension.

3. Assess the pharmacokinetics parameters of Kanarb (Fimasartan), manufactured by Boryung Pharmaceutical Co., Ltd, Republic of Korea in adult patients with arterial hypertension I-II stage after a single dose.

Starting dose of Kanarb (Fimasartan), manufactured by Boryung Pharmaceutical Co., Ltd, Republic of Korea is 60 mg, orally, once a day in the morning.

The planned study duration for each subject is 18 weeks maximum:

The screening period could takes up to 2 weeks (including the 1-week "wash-out" period ) - the screening period duration depends on the prior anti-hypertensive therapy:

• "naive" subjects who never received therapy (which must be reflected in the source documents), may be randomized after completion of all screening procedures;

• Subjects receiving anti-hypertensive therapy which may be discontinued without prior dose reduction must undergo a 7 days "wash-out" period, so the screening period will take at least 7 days;

• Subjects, receiving anti-hypertensive therapy which requires dose reduction before discontinuation must undergo the 7 days "wash-out" period after the last dose administration, so the screening period will consist of dose reduction period and a "wash-out" period.

Treatment period - 12 weeks. Follow-up period - 4 weeks. The subjects will visit the clinical site every 4 weeks to measure ABP. The dose will be doubled in case if SBP ≥140 mmHg or DBP ≥90 mmHg at Visit 3 (Day 28) or at Visit 4 (Day 56).

If necessary, the dose of the study drug may be increased based on the assessment of patient's condition performed at the phone contact (Day14±3). Patient may be called for an unscheduled visit for treatment adjustment (decided individually, with possibility of dose titration as per investigator's judgment, indicated in source documents).

When possibilities are, the patient should be administrated by the study medication at the same time in the morning. Governing conditions for defining the time of the drug administration is the subject comfort and the time of its visits the research center.

If laboratory tests are scheduled, a patient should come to the research center fasting (food is prohibited for 8 hours before the visit).

All of the clinical evaluations are conducted on the next morning after taking the medication. On the visit day a patient comes to the research center not taking the drug, and after all the planned procedures are conducted the patient is administrated by the drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 179 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label, Randomized, Multicenter, Efficacy and Safety Evaluating Study to Compare Kanarb (Fimasartan), Manufactured by Boryung Pharmaceutical Co., Ltd, Republic of Korea, Tablets 60/120 mg and Cozaar® (Losartan), Manufactured by MERCK SHARP & DOHME B.V., Netherlands, Tablet 50/100 mg in Adult Patients With Grade I-II Arterial Hypertension
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Kanarb (Fimasartan) 88 subjects will receive Kanarb (Fimasartan), manufactured by Boryung Pharmaceutical Co., Ltd, Republic of Korea, tablets 60/120 mg for 12 weeks	Drug: Fimasartan; Starting dose of Kanarb (Fimasartan) is 60 mg, orally, once a day in the morning. The subjects will visit the clinical site every 4 weeks to measure Arterial blood pressure (ABP). The dose will be doubled in case if SBP ≥140 mmHg or DBP ≥90 mmHg at Visit 3 (Day 28) or at Visit 4 (Day 56). If necessary, the dose of the study drug may be increased based on the assessment of patient's condition performed at the phone contact (Day14±3). Patient may be called for an unscheduled visit for treatment adjustment (decided individually, with possibility of dose titration as per investigator's judgment, indicated in source documents). When possibilities are, the patient should be administrated by the study medication at the same time in the morning.; Other Names: Kanarb
Active Comparator: Cozaar® (Losartan) 88 subjects will receive Cozaar® (Losartan), manufactured by MERCK SHARP & DOHME B.V., Netherlands, tablets 50/100 mg for 12 weeks	Drug: Losartan; Cozaar® (Losartan), manufactured by MERCK SHARP & DOHME B.V., Netherlands, tablets 50/100 mg; Other Names: Cozaar®

Outcome Measures

Primary Outcome Measures

1. Change in Systolic Blood Pressure (SBP) After 12 Weeks of Treatment [Baseline and week 12 of treatment]

   The value of SBP (seated) to be registered was mean of the 3 measurements performed with interval no less than 1 minute using the manual (mercury or mechanic) tonometer after 5 minutes rest. "Change" was calculated as (Value of SBP at week 12 minus Value of SBP at baseline).

Secondary Outcome Measures

1. Change in Diastolic Blood Pressure (DBP) After 4 Weeks of Treatment [Baseline and week 4 of treatment]

   The value of DBP (seated) to be registered was mean of the 3 measurements performed with interval no less than 1 minute using the manual (mercury or mechanic) tonometer after 5 minutes rest. "Change" was calculated as (Value of DBP at week 4 minus Value of SBP at baseline).

2. Change in DBP After 8 Weeks of Treatment [Baseline and week 8 of treatment]

   The value of DBP (seated) to be registered was mean of the 3 measurements performed with interval no less than 1 minute using the manual (mercury or mechanic) tonometer after 5 minutes rest. "Change" was calculated as (Value of DBP at week 8 minus Value of SBP at baseline).

3. Change in DBP After 12 Weeks of Treatment [Baseline and week 12 of treatment]

   The value of DBP (seated) to be registered was mean of the 3 measurements performed with interval no less than 1 minute using the manual (mercury or mechanic) tonometer after 5 minutes rest. "Change" was calculated as (Value of DBP at week 12 minus Value of SBP at baseline).

4. Change in SBP After 4 Weeks of Treatment [Baseline and week 4 of treatment]

   The value of SBP (seated) to be registered was mean of the 3 measurements performed with interval no less than 1 minute using the manual (mercury or mechanic) tonometer after 5 minutes rest. "Change" was calculated as (Value of SBP at week 4 minus Value of SBP at baseline).

5. Change in SBP After 8 Weeks of Treatment [Baseline and week 8 of treatment]

   The value of SBP( seated) to be registered was mean of the 3 measurements performed with interval no less than 1 minute using the manual (mercury or mechanic) tonometer after 5 minutes rest. "Change" was calculated as (Value of SBP at week 8 minus Value of SBP at baseline).

6. Number of Subjects Who Responded on Therapy [Week 12 of treatment]

   The subject will be considered a responder if SBP (when seated) <140 mmHg or SBP decrease is >10% from baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects of both sex aged 18-75 inclusively.

2. Subjects who signed their written Informed Consent for participation in the study and willing to adhere to all Protocol procedures.

3. Subjects with documented diagnosis of grade I-II primary arterial hypertension within at least 3 months before screening.

4. Systolic blood pressure (SBP) (when seated) at Screening (Day -14)

• For subjects administered with anti-hypertensive therapy: SBP ≤ 179 Hg

• For subjects receiving no anti-hypertensive therapy (so called 'naïve' patients): 140≥SBP ≤179.

1. As per investigator's judgment, subjects with controlled arterial hypertension must benefit from the therapy switch to Kanarb (Fimasartan), manufactured by Boryung Pharmaceutical Co., Ltd, Republic of Korea, tablets 60/120 mg and Cozaar® (Losartan), manufactured by MERCK SHARP & DOHME B.V., Netherlands, .

2. For subjects administered with anti-hypertensive drugs: the anti-hypertensive drug may be safely cancelled during the "wash-out" period according to the investigator's judgment.

3. For women of child-bearing potential: negative urine pregnancy test at screening (Day -14). 8. Systolic blood pressure (SBP) (when seated) at Randomization (Day 0) ≥140 mmHg and ≤179 mmHg.

4. For women of child-bearing potential: negative urine pregnancy test at Randomization (Day 0)

Exclusion Criteria:

1. Grade III Arterial Hypertension.

2. Arterial hypotension (SPB ≤100 mm Hg) at Screening (Day -14) and/or Randomization (Day 0).

3. Subjects needing treatment with more than one anti-hypertensive drug (more than one active substance, including complex drugs).

4. Secondary (symptomatic) arterial hypertension.

5. Known bilateral renal arterial stenosis or unilateral renal arterial stenosis.

6. Hyperpotassemia >5,0 mmol/l (as per blood biochemistry results at Screening).

7. Primary hyperaldosteronism.

8. Known hypersensitivity to angiotensin-II receptors antagonists or any other study drug or comparator component.

9. Contraindications for use of angiotensin-II receptors antagonists.

10. Myocardial infarction and or unstable angina, and/or acute cerebrovascular accident/transient ischemic attack, and/or percutaneous coronary intervention, and/or coronary arterial bypass graft, acute coronary arteries involvement, and/or obliterative vascular atherosclerosis of low extremities, and/or grade III and IV retinopathy in anamnesis.

11. Clinically significant cardiac valves damage.

12. Cardiomyopathies

13. Chronic Heart failure (CHF) (except for CHF FC I NYHA).

14. Creatinine clearance less than 60 ml/min/1.73m2 calculated by Cockroft-Gault formula.

15. Known moderate to severe hepatic insufficiency and/or transaminase increase: AST and/or ALT ≥2*ULN.

16. History of infections (HIV, hepatitis B or C, syphilis).

17. Uncontrolled Diabetes mellitus, Glycosylated hemoglobin level (HbA1c) >7%.

18. Severe systemic diseases, such as gastro-intestinal tract diseases, autoimmune disorders, blood disorders and other conditions which may affect on the study drugs' absorption, distribution and and excretion.

19. Clinically significant abnormalities of laboratory parameters.

20. Drug or alcohol addiction, psychiatric disorders.

21. Medical history of oncological disease within 5 years before screening.

22. Subjects with biliary tracts obstruction.

23. Subjects with genetic disorders, such as galactose intolerance, congenital lactase insufficiency and glucose-galaclose malabsorption syndrome.

24. Any other acute disease or progression and/or decompensation at the moment of enrollment

25. Necessity to administer or administration of prohibited concomitant drugs from the "List of Prohibited Drugs" within 14 days before enrollment

26. Pregnancy or breast-feeding period; fertile women not using adequate contraception methods

27. Participation in another clinical trial within 3 months before Screening.

28. Other medical or psychiatric conditions or lab abnormalities that may increase potential risk associated with study participation and IP administration, or that may affect study results interpretation and as per investigator's judgment, make the subject ineligible.

29. Study site personnel or Sponsor's representatives immediately involved in the study.

30. Subjects, excluded from the study may not be included in it again.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Federal State Institution "Russian Cardiology Research and Production Complex" of the Ministry of Health and Social Development of the Russian Federation (FSI "Cardiology" Russian Healthcare Ministry)	Moscow		Russian Federation
2	Moscow Health Department "City Clinical Hospital № 81"	Moscow		Russian Federation
3	State Research Center for Preventive Medicine of Ministry of Health of the Russian gederation	Moscow		Russian Federation
4	St. Petersburg State health agency "City Hospital number 38 it. NA Semashko "	Pushkin		Russian Federation
5	St. Petersburg State healthcare Institution "City Hospital number 28" "Maximilianovskaya"	St. Petersburg		Russian Federation	190000
6	Clinical Hospital n. a. St. Luka	St. Petersburg		Russian Federation
7	Federal Almazov Medical Research Centre	St. Petersburg		Russian Federation
8	St. Petersburg State Healthcare Institution 'Diagnostic Centre #85'	St. Petersburg		Russian Federation
9	St. Petersburg State Institution of Health "City Hospital № 15"	St. Petersburg		Russian Federation
10	St. Petersburg State Institution of Healthcare "Pokrovskaya City Hospital"	St. Petersburg		Russian Federation
11	State Budget Education Institution of Higher Professional Education "North-Western State Medical University named after I.I. Mechnikov" on base St. Petersburg State Institution of Healthcare "Pokrovskaya City Hospital"	St. Petersburg		Russian Federation
12	State Budget Education Institution of Higher Professional Education "North-Western State Medical University named after I.I. Mechnikov", the department faculty and hospital care, court number 5	St. Petersburg		Russian Federation
13	Troitsk City Hospital	Troitsk		Russian Federation

Sponsors and Collaborators

• R-Pharm
• Covance
• Boryung Pharmaceutical Co., Ltd

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: R-Pharm
• ClinicalTrials.gov Identifier: NCT02248961
• Other Study ID Numbers: CC09042014
• First Posted: Sep 25, 2014
• Last Update Posted: May 6, 2019
• Last Verified: Feb 1, 2019

• Additional relevant MeSH terms: Hypertension; Losartan

Study Results

Participant Flow

Recruitment Details	Participants recruitment was conducted in 13 clinical sites of Moscow and Saint-Petersburg between May and October of 2014
Pre-assignment Detail	Duration of screening period was up to 14 days depended on prior antihypertensive treatment. 184 patients were screened, 179 randomized.

Arm/Group Title	Kanarb (Fimasartan)	Cozaar® (Losartan)
Arm/Group Description	60/120 mg Kanarb (Fimasartan) administered orally once a day in the morning for 12 weeks period	50/100 mg Cozaar® (Losartan) administered orally once a day for 12 week period
Period Title: Overall Study
STARTED	89	90
COMPLETED	86	88
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Kanarb (Fimasartan)	Cozaar® (Losartan)	Total
Arm/Group Description	60/120 mg Kanarb (Fimasartan) administered orally once a day in the morning for 12 weeks period	50/100 mg Cozaar® (Losartan) administered orally once a day for 12 week period	Total of all reporting groups
Overall Participants	89	90	179
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53.4	53.8	53.6
Sex: Female, Male (Count of Participants)
Female	30 33.7%	34 37.8%	64 35.8%
Male	59 66.3%	56 62.2%	115 64.2%
Race/Ethnicity, Customized (Count of Participants)
European	87 97.8%	90 100%	177 98.9%
Asian	2 2.2%	0 0%	2 1.1%
BMI (kg/m^2) [Mean (Full Range) ]
Mean (Full Range) [kg/m^2]	29.4	28.9	29.1
Arterial hypertension (AH) duration (years) [Mean (Full Range) ]
Mean (Full Range) [years]	5.8	6.2	6.0
Hypertension grade (Count of Participants)
Grade I	20 22.5%	27 30%	47 26.3%
Grade II	69 77.5%	63 70%	132 73.7%
Chronic heart failure (CHF) NYHA Class I (Count of Participants)
Count of Participants [Participants]	10 11.2%	12 13.3%	22 12.3%
Prior therapy for arterial hypertension (Count of Participants)
Count of Participants [Participants]	55 61.8%	46 51.1%	101 56.4%
Smoking history (Count of Participants)
Smoker	19 21.3%	62 68.9%	81 45.3%
Has never smoked	63 70.8%	21 23.3%	84 46.9%
Smoker-in-the-past	7 7.9%	7 7.8%	14 7.8%
Alcohol history (Count of Participants)
Drinking	52 58.4%	57 63.3%	109 60.9%
Never-drinking	25 28.1%	23 25.6%	48 26.8%
Drinking-in-the-past	12 13.5%	9 10%	21 11.7%
Unknown	0 0%	1 1.1%	1 0.6%

Outcome Measures

1. Primary Outcome

Title	Change in Systolic Blood Pressure (SBP) After 12 Weeks of Treatment
Description	The value of SBP (seated) to be registered was mean of the 3 measurements performed with interval no less than 1 minute using the manual (mercury or mechanic) tonometer after 5 minutes rest. "Change" was calculated as (Value of SBP at week 12 minus Value of SBP at baseline).
Time Frame	Baseline and week 12 of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set Population (FAS) - those subjects from Intent-to-treat population (ITT, all randomized patients), who had at least one assessment for efficacy analysis after the start of therapy. Last observation carried forward (LOCF) imputation method.

Arm/Group Title	Kanarb (Fimasartan)	Cozaar® (Losartan)
Arm/Group Description	60/120 mg Kanarb (Fimasartan) administered orally once a day in the morning for 12 weeks period	50/100 mg Cozaar® (Losartan) administered orally once a day for 12 week period
Measure Participants	89	90
SBP at Baseline	152.9 (5.9)	151.9 (5.9)
Change from Baseline at Week 12	-25.2 (8.6)	-24.3 (7.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kanarb (Fimasartan), Cozaar® (Losartan)
	Comments	The null hypothesis (H0) is that there is a decrease in SBP on the background treatment with Kanarb (fimasartan), that is at least 5.5 mmHg lower compared to Cozaar® (losartan). Test of the hypotheses was performed using mixed linear models, where the site effect was considered a random effect, and the treatment group effect was considered a fixed effect. Baseline SBP on the study arm was included into the model as a covariate (a fixed effect) in all cases.
	Type of Statistical Test	Other
	Comments	It was calculated that at least 140 patients (70 patients per group) must be enrolled into the study to achieve 80% power. With regard to 20% of patients withdrawn prematurely or data not suitable for analysis, it was necessary to include at least 176 patients (88 per group) into the study.
Statistical Test of Hypothesis	p-Value	=0.390
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.18
	Confidence Interval	(1-Sided) 95%; to 1.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.00
	Estimation Comments

2. Secondary Outcome

Title	Change in Diastolic Blood Pressure (DBP) After 4 Weeks of Treatment
Description	The value of DBP (seated) to be registered was mean of the 3 measurements performed with interval no less than 1 minute using the manual (mercury or mechanic) tonometer after 5 minutes rest. "Change" was calculated as (Value of DBP at week 4 minus Value of SBP at baseline).
Time Frame	Baseline and week 4 of treatment

Outcome Measure Data

Analysis Population Description

All randomized patients, who had at least one assessment for efficacy analysis after the start of therapy. One patient (Kanarb (fimasartan) treatment group) was withdrawn from the study by the time of assessment at week 4.

Arm/Group Title	Kanarb (Fimasartan)	Cozaar® (Losartan)
Arm/Group Description	60/120 mg Kanarb (Fimasartan) administered orally once a day in the morning for 12 weeks period	50/100 mg Cozaar® (Losartan) administered orally once a day for 12 week period
Measure Participants	89	90
DBP at Baseline	88.7 (8.1)	89.6 (6.9)
Change from Baseline at Week 4	-9.5 (9.1)	-7.4 (7.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kanarb (Fimasartan), Cozaar® (Losartan)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.018
	Comments
	Method	Mixed Models Analysis
	Comments	The investigational site was included as random effect. The baseline levels of SBP and the treatment group were included as fixed effects.

3. Secondary Outcome

Title	Change in DBP After 8 Weeks of Treatment
Description	The value of DBP (seated) to be registered was mean of the 3 measurements performed with interval no less than 1 minute using the manual (mercury or mechanic) tonometer after 5 minutes rest. "Change" was calculated as (Value of DBP at week 8 minus Value of SBP at baseline).
Time Frame	Baseline and week 8 of treatment

Outcome Measure Data

Analysis Population Description

All randomized patients, who had at least one assessment for efficacy analysis after the start of therapy. One patient (Kanarb (fimasartan) treatment group) was withdrawn from the study by the time of assessment at week 8.

Arm/Group Title	Kanarb (Fimasartan)	Cozaar® (Losartan)
Arm/Group Description	60/120 mg Kanarb (Fimasartan) administered orally once a day in the morning for 12 weeks period	50/100 mg Cozaar® (Losartan) administered orally once a day for 12 week period
Measure Participants	89	90
DBP at Baseline	88.7 (8.1)	89.6 (6.9)
Change from Baseline at Week 8	-10.3 (9.5)	-10.7 (7.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kanarb (Fimasartan), Cozaar® (Losartan)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.579
	Comments
	Method	Mixed Models Analysis
	Comments	The investigational site was included as random effect. The baseline levels of SBP and the treatment group were included as fixed effects.

4. Secondary Outcome

Title	Change in DBP After 12 Weeks of Treatment
Description	The value of DBP (seated) to be registered was mean of the 3 measurements performed with interval no less than 1 minute using the manual (mercury or mechanic) tonometer after 5 minutes rest. "Change" was calculated as (Value of DBP at week 12 minus Value of SBP at baseline).
Time Frame	Baseline and week 12 of treatment

Outcome Measure Data

Analysis Population Description

One patient (Kanarb (fimasartan) treatment group) was withdrawn from the study by the time of assessment at week 12

Arm/Group Title	Kanarb (Fimasartan)	Cozaar® (Losartan)
Arm/Group Description	60/120 mg Kanarb (Fimasartan) administered orally once a day in the morning for 12 weeks period	50/100 mg Cozaar® (Losartan) administered orally once a day for 12 week period
Measure Participants	89	88
DBP at Baseline	88.7 (8.1)	89.6 (6.9)
Change from Baseline at Week 12	-10.6 (8.8)	-11.3 (7.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kanarb (Fimasartan), Cozaar® (Losartan)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.466
	Comments
	Method	Mixed Models Analysis
	Comments	The investigational site was included as random effect. The baseline levels of SBP and the treatment group were included as fixed effects.

5. Secondary Outcome

Title	Change in SBP After 4 Weeks of Treatment
Description	The value of SBP (seated) to be registered was mean of the 3 measurements performed with interval no less than 1 minute using the manual (mercury or mechanic) tonometer after 5 minutes rest. "Change" was calculated as (Value of SBP at week 4 minus Value of SBP at baseline).
Time Frame	Baseline and week 4 of treatment

Outcome Measure Data

Analysis Population Description

One patient (Kanarb (fimasartan) treatment group) was withdrawn from the study by the time of assessment at week 4

Arm/Group Title	Kanarb (Fimasartan)	Cozaar® (Losartan)
Arm/Group Description	60/120 mg Kanarb (Fimasartan) administered orally once a day in the morning for 12 weeks period	50/100 mg Cozaar® (Losartan) administered orally once a day for 12 week period
Measure Participants	89	90
SBP at Baseline	152.9 (5.9)	151.9 (5.9)
Change from Baseline at Week 4	-19.7 (10.3)	-17.6 (10.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kanarb (Fimasartan), Cozaar® (Losartan)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.118
	Comments
	Method	Mixed Models Analysis
	Comments	The investigational site was included as random effect. The baseline levels of SBP and the treatment group were included as fixed effects.

6. Secondary Outcome

Title	Change in SBP After 8 Weeks of Treatment
Description	The value of SBP( seated) to be registered was mean of the 3 measurements performed with interval no less than 1 minute using the manual (mercury or mechanic) tonometer after 5 minutes rest. "Change" was calculated as (Value of SBP at week 8 minus Value of SBP at baseline).
Time Frame	Baseline and week 8 of treatment

Outcome Measure Data

Analysis Population Description

One patient (Kanarb (fimasartan) treatment group) was withdrawn from the study by the time of assessment at week 8

Arm/Group Title	Kanarb (Fimasartan)	Cozaar® (Losartan)
Arm/Group Description	60/120 mg Kanarb (Fimasartan) administered orally once a day in the morning for 12 weeks period	50/100 mg Cozaar® (Losartan) administered orally once a day for 12 week period
Measure Participants	89	90
SBP at Baseline	152.9 (5.9)	151.9 (5.9)
Change from Baseline at Week 8	-23.5 (9.0)	-23.9 (8.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kanarb (Fimasartan), Cozaar® (Losartan)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.662
	Comments
	Method	Mixed Models Analysis
	Comments	The investigational site was included as random effect. The baseline levels of SBP and the treatment group were included as fixed effects.

7. Secondary Outcome

Title	Number of Subjects Who Responded on Therapy
Description	The subject will be considered a responder if SBP (when seated) <140 mmHg or SBP decrease is >10% from baseline.
Time Frame	Week 12 of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set Population (FAS) - those subjects from Intent-to-treat population (ITT, all randomized patients), who had at least one assessment for efficacy analysis after the start of therapy. Last observation carried forward (LOCF) imputation method.

Arm/Group Title	Kanarb (Fimasartan)	Cozaar® (Losartan)
Arm/Group Description	60/120 mg Kanarb (Fimasartan) administered orally once a day in the morning for 12 weeks period	50/100 mg Cozaar® (Losartan) administered orally once a day for 12 week period
Measure Participants	89	90
Count of Participants [Participants]	85 95.5%	90 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kanarb (Fimasartan), Cozaar® (Losartan)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.143
	Comments
	Method	Mantel Haenszel
	Comments

Adverse Events

Time Frame	18 weeks
Adverse Event Reporting Description	The number and percent of subjects and number and group of AEs will be performed within every organ/system group
Arm/Group Title	Kanarb (Fimasartan)		Cozaar® (Losartan)
Arm/Group Description	60/120 mg Kanarb (Fimasartan) administered orally once a day in the morning for 12 weeks period		50/100 mg Cozaar® (Losartan) administered orally once a day for 12 week period
All Cause Mortality
	Kanarb (Fimasartan)		Cozaar® (Losartan)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/89 (0%)		0/90 (0%)
Serious Adverse Events
	Kanarb (Fimasartan)		Cozaar® (Losartan)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/89 (0%)		0/90 (0%)
Other (Not Including Serious) Adverse Events
	Kanarb (Fimasartan)		Cozaar® (Losartan)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/89 (22.5%)		15/90 (16.7%)
Blood and lymphatic system disorders
Anaemia	1/89 (1.1%)		0/90 (0%)
Hypochromic anaemia	0/89 (0%)		1/90 (1.1%)
Cardiac disorders
Atrial fibrillation	0/89 (0%)		1/90 (1.1%)
Eye disorders
Conjunctival oedema	0/89 (0%)		1/90 (1.1%)
Dry eye	0/89 (0%)		1/90 (1.1%)
Gastrointestinal disorders
Irritable bowel syndrome	0/89 (0%)		1/90 (1.1%)
Nausea	4/89 (4.5%)		1/90 (1.1%)
General disorders
Diarrhoea	1/89 (1.1%)		0/90 (0%)
Infections and infestations
Bronchitis	0/89 (0%)		1/90 (1.1%)
Nasopharyngitis	1/89 (1.1%)		2/90 (2.2%)
Pharyngitis	1/89 (1.1%)		0/90 (0%)
Respiratory tract infection viral	1/89 (1.1%)		1/90 (1.1%)
Rhinitis	1/89 (1.1%)		0/90 (0%)
Injury, poisoning and procedural complications
Contusion	1/89 (1.1%)		0/90 (0%)
Investigations
Alanine aminotransferase increased	2/89 (2.2%)		1/90 (1.1%)
Aspartate aminotransferase increased	3/89 (3.4%)		1/90 (1.1%)
Blood alkaline phosphatase increased	0/89 (0%)		1/90 (1.1%)
Blood cholesterol increased	1/89 (1.1%)		0/90 (0%)
Blood creatine phosphokinase increased	1/89 (1.1%)		1/90 (1.1%)
Blood pressure increased	1/89 (1.1%)		0/90 (0%)
Creatinine renal clearance decreased	1/89 (1.1%)		0/90 (0%)
Low density lipoprotein increased	1/89 (1.1%)		0/90 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/89 (0%)		1/90 (1.1%)
Hyperkalaemia	0/89 (0%)		1/90 (1.1%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/89 (0%)		1/90 (1.1%)
Nervous system disorders
Dizziness	1/89 (1.1%)		1/90 (1.1%)
Headache	4/89 (4.5%)		3/90 (3.3%)
Renal and urinary disorders
Renal impairment	0/89 (0%)		1/90 (1.1%)
Skin and subcutaneous tissue disorders
Pruritus	1/89 (1.1%)		0/90 (0%)
Urticaria	1/89 (1.1%)		0/90 (0%)
Vascular disorders
Hypertensive crisis	0/89 (0%)		1/90 (1.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Any study related information could be made public availiable only after Sponsors written permission.