Open-Label Long-Term Safety and Efficacy Study of Fixed Dose Combination of Nifedipine Gastrointestinal Therapeutic System and Candesartan Cilexetil in Subjects With Moderate to Severe Essential Hypertension

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01788358
• Collaborator: (none)
• Enrollment: 508
• Locations: 82
• Arm: 1
• Actual Duration (Months): 14.5
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study examines the long term safety and efficacy of the Fixed Dose combination BAY98-7106 (nifedipine plus candesartan primarily at the highest dose in development) in patients with moderate to severe hypertension.

Patients meeting the entry criteria, will receive the Fixed Dose combination for 28 weeks, including 8 weeks with stepwise dose increase up to the high target dose. The first 200 subjects completing 28 weeks will continue treatment for additional 24 weeks (52 weeks in total).

Subjects who do not tolerate an increased dose will be treated at their highest tolerable dose.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106); Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106); Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106); Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 508 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multicenter, Open-Label, Long-Term Safety and Efficacy Study of the Fixed Dose Combination of Nifedipine Gastrointestinal Therapeutic System and Candesartan Cilexetil in Adult Subjects With Moderate to Severe Essential Hypertension
• Actual Study Start Date: Feb 14, 2013
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106) Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).

Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106); Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 30/8 mg, orally once daily; Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106); Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 30/16 mg, orally once daily; Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106); Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 60/16 mg, orally once daily; Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106); Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 60/32 mg, orally once daily

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With All Treatment-emergent Adverse Events (TEAEs) and Drug-related TEAEs up to Week 28 [From the time of first study drug administration up to Week 28]

   An adverse event (AE) is any untoward medical occurrence (that is, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication.

2. Number of Subjects With Treatment-emergent Adverse Events (TEAEs) of Special Interest up to Week 28 [From the time of first study drug administration up to Week 28]

   An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication. TEAEs of special interest included the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as oedema, headache, and flushing). Only subjects who had TEAEs of special interest as mild, moderate or severe were reported.

3. Number of Subjects With All Treatment-emergent Adverse Events (TEAEs) and Drug-related TEAEs up to Week 52/End of Study (EOS) [From the time of first study drug administration up to Week 52/EOS]

   An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication.

4. Number of Subjects With Treatment-emergent Adverse Events (TEAEs) of Special Interest up to Week 52/End of Study (EOS) [From the time of study treatment up to Week 52/EOS]

   An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication. TEAEs of special interest included the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as oedema, headache, and flushing). Only subjects who had TEAEs of special interest as mild, moderate or severe were reported.

Secondary Outcome Measures

1. Number of Subjects With Clinically Relevant Changes in Laboratory Parameters [Baseline (Week 0) up to Week 52/EOS]

   Laboratory evaluations of blood and urine samples were performed, including hematology (hematocrit, hemoglobin, red blood cells count, white blood cells count, neutrophils, lymphocytes, monocytes, eosinophils, basophils, platelets), blood chemistry (sodium, potassium, chloride, bicarbonate, uric acid, total protein, albumin, calcium, blood urea nitrogen, creatinine, aspartate transaminase, alanine transaminase, lactate dehydrogenase, gamma glutamyl transferase, alkaline phosphatase, creatine kinase, total bilirubin, direct bilirubin, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, fasting glucose), urinalysis (pH, blood, specific gravity, glucose, protein, cells/sediment). A laboratory test abnormality considered clinically relevant, for example, causing withdrawal by subject, requiring treatment or causing apparent clinical manifestations, or judged relevant by the investigator, were reported as AEs.

2. Change From Baseline In Mean Seated Systolic Blood Pressure (MSSBP) At Weeks 28 And 52 [Baseline (Week 0), Weeks 28 and 52]

3. Change From Baseline in Mean Seated Diastolic Blood Pressure (MSDBP) at Weeks 28 and 52 [Baseline (Week 0), Weeks 28 and 52]

4. Blood Pressure Control Rate at Weeks 28 and 52 [Weeks 28 and 52]

   Control rate was defined as the percentage of subjects that reached a predetermined blood pressure (BP) target of BP less than (<) 140/90 mmHg.

5. Blood Pressure Response Rate at Weeks 28 and 52 [Weeks 28 and 52]

   Response rate was defined as the percentage of subjects who achieved a systolic blood pressure response (MSSBP of <140 mmHg or a reduction of MSSBP of more than (>) 20 mmHg from baseline value), or a diastolic blood pressure response (MSDBP of <90 mmHg or a reduction of MSDBP of >10 mmHg from baseline value).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have moderate to severe essential hypertension (Grade 2 or Grade 3, WHO classifications). At Visit 1, subjects not treated with antihypertensive medications are to have MSSBP of >/= 160 mmHg and < 200 mmHg, as measured by a calibrated electronic BP measuring device. For other subjects who are treated with antihypertensive medication before, they should have MSSBP >/= 160 mmHg and <200 mmHg after wash out.

• Women of childbearing potential and men must agree to use adequate contraception other than hormonal contraceptives when sexually active

Exclusion Criteria:

• Mean seated systolic blood pressure >/= 200 mmHg and/or mean seated diastolic blood pressure >/= 120 mm/Hg

• Mean seated diastolic blood pressure < 60 mm/Hg

• Differences greater than 20 mmHg for systolic blood pressure and 10 mmHg for diastolic blood pressure are present on 3 consecutive blood pressure readings at visit 0

• Any history of hypertensive emergency

• Evidence of secondary hypertension such as coarctation of the aorta, pheochromocytoma, hyperaldosteronism, etc.

• Cerebrovascular ischemic event (stroke, transient ischemic attack [TIA])within the previous 12 months

• History of intracerebral hemorrhage or subarachnoid hemorrhage

• History of hypertensive retinopathy - known Keith-Wagener Grade III or IV

• Any history of heart failure, New York Heart Association (NYHA) classification III or IV

• Severe coronary heart disease as manifest by a history of myocardial infarction or unstable angina in the last 6 months prior to visit 0

• Type 1 diabetes mellitus (DM) or poorly controlled Type 2 DM as evidenced by HbA1C of greater than 9% on visit 0.

• Hyperkalemia: potassium above the upper limit of normal in the laboratory range

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Foley	Alabama	United States	36535
2		Carmichael	California	United States	95608
3		Los Angeles	California	United States	90057
4		Spring Valley	California	United States	91978
5		Milford	Connecticut	United States	06460
6		Coral Gables	Florida	United States	33114-4192
7		Hallandale Beach	Florida	United States	33009
8		Hollywood	Florida	United States	33083
9		Jacksonville	Florida	United States	32216
10		Jupiter	Florida	United States	33458
11		Tampa	Florida	United States	33606
12		Atlanta	Georgia	United States	30338
13		Valparaiso	Indiana	United States	46383
14		Newton	Kansas	United States	67114
15		Wichita	Kansas	United States	67205
16		Lexington	Kentucky	United States	40504
17		New Orleans	Louisiana	United States	70119
18		Auburn	Maine	United States	04240
19		Elkridge	Maryland	United States	21075
20		Brockton	Massachusetts	United States	02301
21		Saint Louis	Missouri	United States	63141
22		Shelby	North Carolina	United States	28150
23		Cincinnati	Ohio	United States	45224
24		Cincinnati	Ohio	United States	45245
25		Cincinnati	Ohio	United States	45246
26		Columbus	Ohio	United States	43213
27		Greenville	South Carolina	United States	29615
28		Mount Pleasant	South Carolina	United States	29464
29		Rapid City	South Dakota	United States	57702
30		Nashville	Tennessee	United States	37203
31		New Tazewell	Tennessee	United States	37825
32		Beaumont	Texas	United States	77701
33		Bryan	Texas	United States	77802
34		Carrollton	Texas	United States	75010
35		Dallas	Texas	United States	75230
36		San Antonio	Texas	United States	78229
37		Salt Lake City	Utah	United States	84109
38		Salt Lake City	Utah	United States	84121
39		Kenosha	Wisconsin	United States	53142
40		Moorsel	Oost-Vlaanderen	Belgium	9310
41		Wetteren	Oost-Vlaanderen	Belgium	9230
42		Steenokkerzeel	Vlaams Brabant	Belgium	1820
43		Deurne		Belgium	2100
44		HAM		Belgium	3545
45		Burnaby	British Columbia	Canada	V5G 1T4
46		Langley	British Columbia	Canada	V3A 4H9
47		Vancouver	British Columbia	Canada	V5Z 1K3
48		Brampton	Ontario	Canada	L6T 0G1
49		Burlington	Ontario	Canada	L7M 4Y1
50		Etobicoke	Ontario	Canada	M8V 3X8
51		London	Ontario	Canada	N5W 6A2
52		Newmarket	Ontario	Canada	L3Y 5G8
53		Sarnia	Ontario	Canada	N7T 4X3
54		Stayner	Ontario	Canada	L0M 1S0
55		Toronto	Ontario	Canada	M4S 1Y2
56		Toronto	Ontario	Canada	M9V 4B4
57		Woodstock	Ontario	Canada	N4S 4G3
58		Pointe-Claire	Quebec	Canada	H9R 3J1
59		Ste-Foy	Quebec	Canada	G1W 1S2
60		Frankfurt	Hessen	Germany	60313
61		Bochum	Nordrhein-Westfalen	Germany	44787
62		Magdeburg	Sachsen-Anhalt	Germany	39104
63		Görlitz	Sachsen	Germany	02826
64		Leipzig	Sachsen	Germany	04103
65		Berlin		Germany	12627
66		Dresden		Germany
67		Gdynia		Poland	81-384
68		Katowice		Poland	40-040
69		Warszawa		Poland	01-192
70		Wroclaw		Poland	50-088
71		Reading	Berkshire	United Kingdom	RG2 0TG
72		Chesterfield	Derbyshire	United Kingdom	S40 4AA
73		Blackpool	Lancashire	United Kingdom	FY3 7EN
74		Bath	Somerset	United Kingdom	BA3 2UH
75		Bury St Edmonds	Suffolk	United Kingdom	IP30 9QU
76		Coventry	Warwickshire	United Kingdom	CV6 4DD
77		Birmingham	West Midlands	United Kingdom	B15 2SQ
78		Cardiff		United Kingdom	CF14 5GJ
79		Chorley		United Kingdom	PR7 7NA
80		Glasgow		United Kingdom	G20 OSP
81		Liverpool		United Kingdom	L22 0LG
82		Manchester		United Kingdom	M15 6SX

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT01788358
• Other Study ID Numbers: 14801; 2012-004515-32
• First Posted: Feb 11, 2013
• Last Update Posted: Oct 24, 2017
• Last Verified: Sep 1, 2017

• Keywords provided by Bayer: Drug combination; Nifedipine GITS; Candesartan Cilexetil; Hypertension; Combination therapy
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Candesartan; Candesartan cilexetil; Nifedipine

Study Results

Participant Flow

Recruitment Details	The study was conducted at 70 study centers between 14 February 2013 (first subject first visit) and 1 May 2014 (last subject last visit).
Pre-assignment Detail	Of 753 subjects screened, 245 subjects were not enrolled, due to screen failure for 215 subjects, consent withdrawal by 23 subjects, protocol violation by 5 subjects, 1 subject was lost to follow-up and recruitment stopped for 1 subject. Remaining 508 subjects were enrolled and received at least 1 treatment with study drug.

Arm/Group Title	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Arm/Group Description	Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
Period Title: Overall Study
STARTED	508
Treated	508
Completed Week 28	417
Entered Extension to Week 52	200
Completed Week 52	193
COMPLETED	410
NOT COMPLETED	98

Baseline Characteristics

Arm/Group Title	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Arm/Group Description	Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
Overall Participants	508
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59 (10.2)
Sex: Female, Male (Count of Participants)
Female	186 36.6%
Male	322 63.4%
Systolic blood pressure (millimeter of mercury (mmHg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimeter of mercury (mmHg)]	170.7 (8.9)
Diastolic blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	95.6 (10.4)

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With All Treatment-emergent Adverse Events (TEAEs) and Drug-related TEAEs up to Week 28
Description	An adverse event (AE) is any untoward medical occurrence (that is, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication.
Time Frame	From the time of first study drug administration up to Week 28

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (SAF): All the subjects enrolled into the open-label treatment period and took at least one unit of the study medication.

Arm/Group Title	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Arm/Group Description	Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
Measure Participants	508
All TEAEs	390
Drug-related TEAEs	230

2. Primary Outcome

Title	Number of Subjects With Treatment-emergent Adverse Events (TEAEs) of Special Interest up to Week 28
Description	An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication. TEAEs of special interest included the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as oedema, headache, and flushing). Only subjects who had TEAEs of special interest as mild, moderate or severe were reported.
Time Frame	From the time of first study drug administration up to Week 28

Outcome Measure Data

Analysis Population Description

SAF

Arm/Group Title	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Arm/Group Description	Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
Measure Participants	508
Oedema (mild)	124
Oedema (moderate)	54
Oedema (severe)	7
Headache (mild)	31
Headache (moderate)	15
Flushing (mild)	3
Symptomatic hypotension (mild)	4

3. Primary Outcome

Title	Number of Subjects With All Treatment-emergent Adverse Events (TEAEs) and Drug-related TEAEs up to Week 52/End of Study (EOS)
Description	An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication.
Time Frame	From the time of first study drug administration up to Week 52/EOS

Outcome Measure Data

Analysis Population Description

SAF

Arm/Group Title	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Arm/Group Description	Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
Measure Participants	508
All TEAEs	404
Drug-related TEAEs	238

4. Primary Outcome

Title	Number of Subjects With Treatment-emergent Adverse Events (TEAEs) of Special Interest up to Week 52/End of Study (EOS)
Description	An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication. TEAEs of special interest included the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as oedema, headache, and flushing). Only subjects who had TEAEs of special interest as mild, moderate or severe were reported.
Time Frame	From the time of study treatment up to Week 52/EOS

Outcome Measure Data

Analysis Population Description

SAF

Arm/Group Title	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Arm/Group Description	Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
Measure Participants	508
Oedema (mild)	131
Oedema (moderate)	56
Oedema(severe)	7
Headache (mild)	31
Headache (moderate)	17
Flushing (mild)	3
Symptomatic hypotension (mild)	4

5. Secondary Outcome

Title	Number of Subjects With Clinically Relevant Changes in Laboratory Parameters
Description	Laboratory evaluations of blood and urine samples were performed, including hematology (hematocrit, hemoglobin, red blood cells count, white blood cells count, neutrophils, lymphocytes, monocytes, eosinophils, basophils, platelets), blood chemistry (sodium, potassium, chloride, bicarbonate, uric acid, total protein, albumin, calcium, blood urea nitrogen, creatinine, aspartate transaminase, alanine transaminase, lactate dehydrogenase, gamma glutamyl transferase, alkaline phosphatase, creatine kinase, total bilirubin, direct bilirubin, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, fasting glucose), urinalysis (pH, blood, specific gravity, glucose, protein, cells/sediment). A laboratory test abnormality considered clinically relevant, for example, causing withdrawal by subject, requiring treatment or causing apparent clinical manifestations, or judged relevant by the investigator, were reported as AEs.
Time Frame	Baseline (Week 0) up to Week 52/EOS

Outcome Measure Data

Analysis Population Description

SAF

Arm/Group Title	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Arm/Group Description	Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
Measure Participants	508
Number [Subjects]	0

6. Secondary Outcome

Title	Change From Baseline In Mean Seated Systolic Blood Pressure (MSSBP) At Weeks 28 And 52
Time Frame	Baseline (Week 0), Weeks 28 and 52

Outcome Measure Data

Analysis Population Description

Modified intention-to-treat analysis set (mITT): All the subjects enrolled into the open-label treatment period and took at least one unit of the study medication.

Arm/Group Title	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Arm/Group Description	Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
Measure Participants	508
Baseline	170.7 (8.9)
Change at Week 28	-30.4 (17.7)
Change at Week 52	-30.1 (18.4)

7. Secondary Outcome

Title	Change From Baseline in Mean Seated Diastolic Blood Pressure (MSDBP) at Weeks 28 and 52
Time Frame	Baseline (Week 0), Weeks 28 and 52

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Arm/Group Description	Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
Measure Participants	508
Baseline	95.6 (10.4)
Change at Week 28	-12.7 (10.6)
Change at Week 52	-12.8 (10.7)

8. Secondary Outcome

Title	Blood Pressure Control Rate at Weeks 28 and 52
Description	Control rate was defined as the percentage of subjects that reached a predetermined blood pressure (BP) target of BP less than (<) 140/90 mmHg.
Time Frame	Weeks 28 and 52

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Arm/Group Description	Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
Measure Participants	508
Week 28	51.4
Week 52	51.6

9. Secondary Outcome

Title	Blood Pressure Response Rate at Weeks 28 and 52
Description	Response rate was defined as the percentage of subjects who achieved a systolic blood pressure response (MSSBP of <140 mmHg or a reduction of MSSBP of more than (>) 20 mmHg from baseline value), or a diastolic blood pressure response (MSDBP of <90 mmHg or a reduction of MSDBP of >10 mmHg from baseline value).
Time Frame	Weeks 28 and 52

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Arm/Group Description	Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
Measure Participants	508
Week 28	86.6
Week 52	86.2

Adverse Events

Time Frame	Treatment Emergent Adverse Events (TEAEs) were collected from the time of first study drug administration up to 7 days after Week 52/EOS
Adverse Event Reporting Description	One death reported under SAE happened approximately 6 months after the subject had completed the study due to malignant melanoma of head and neck with metastasis to lung and liver, not related to the treatment.
Arm/Group Title	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Arm/Group Description	Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
All Cause Mortality
	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
	Affected / at Risk (%)	# Events
Total	15/508 (3%)
Blood and lymphatic system disorders
Aplastic anaemia	1/508 (0.2%)	1
Cardiac disorders
Acute myocardial infarction	1/508 (0.2%)	1
Coronary artery disease	1/508 (0.2%)	1
Supraventricular tachycardia	1/508 (0.2%)	1
Gastrointestinal disorders
Colitis	1/508 (0.2%)	1
General disorders
Chest pain	1/508 (0.2%)	1
Pyrexia	1/508 (0.2%)	1
Infections and infestations
Chronic sinusitis	1/508 (0.2%)	1
Injury, poisoning and procedural complications
Ankle fracture	1/508 (0.2%)	1
Joint dislocation	1/508 (0.2%)	2
Musculoskeletal and connective tissue disorders
Back pain	1/508 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/508 (0.2%)	1
Malignant melanoma	1/508 (0.2%)	1
Prostate cancer	1/508 (0.2%)	1
Nervous system disorders
Syncope	1/508 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
	Affected / at Risk (%)	# Events
Total	279/508 (54.9%)
General disorders
Fatigue	18/508 (3.5%)	20
Oedema	55/508 (10.8%)	80
Oedema peripheral	150/508 (29.5%)	239
Infections and infestations
Nasopharyngitis	27/508 (5.3%)	30
Upper respiratory tract infection	25/508 (4.9%)	29
Nervous system disorders
Dizziness	47/508 (9.3%)	55
Headache	47/508 (9.3%)	60

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.