Parallel-Group Comparison of Olmesartan (OLM), Amlodipine (AML) and Hydrochlorothiazid (HCTZ) in Hypertension

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00923091
• Collaborator: (none)
• Enrollment: 2,689
• Locations: 133
• Arms: 8
• Duration (Months): 21
• Patients Per Site: 20.2
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This study is to determine the change in blood pressure from the administration of Olmesartan/Amlodipine/Hydrochlorothiazide triple combinations compared to dual combinations with Olmesartan/Amlodipine.

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension	Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide + placebo; Drug: Olmesartan medoxomil + amlodipine + hydrochlorothiazide + placebo; Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide; Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide; Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide; Drug: olmesartan medoxomil + amlodipine; Drug: olmesartan medoxomil + amlodipine; Drug: olmesartan medoxomil + amlodipine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 2689 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomised, Double-Blind, Parallel-Group Study Evaluating Efficacy and Safety of Co-Administration of Triple Combinations of Olmesartan Medoxomil, Amlodipine Besylate, and Hydrochlorothiazide Compared With Corresponding Olmesartan - Amlodipine Combination in Subjects With Hypertension
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: olmesartan/amlodipine/hydrochlorothiazide 20mg/5mg/12.5mg olmesartan medoxomil 20mg / amlodipine besylate 5 mg / hydrochlorothiazide 12.5mg	Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide + placebo; One olmesartan medoxomil 20 mg + amlodipine 5 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.; Other Names: Azor
Experimental: olmesartan/amlodipine/hydrochlorothiazide 40mg/5mg/12.5mg	Drug: Olmesartan medoxomil + amlodipine + hydrochlorothiazide + placebo; One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.; Other Names: Azor
Experimental: olmesartan/amlodipine/hydrochlorothiazide 40mg/5mg/25mg	Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide; One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day. Two hydrochlorothiazide 12.5 mg tablets taken once per day.; Other Names: Azor Norvasc
Experimental: olmesartan/amlodipine/hydrochlorothiazide 40mg/10mg/12.5mg	Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide; One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.; Other Names: Azor
Experimental: olmesartan/amlodipine/hydrochlorothiazide 40mg/10mg/25mg	Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide; One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day. Two hydrochlorothiazide 12.5 mg tablets taken once per day.; Other Names: Azor
Experimental: olmesartan/amlodipine 20mg/5mg olmesartan medoxomil 20mg / amlodipine besylate 5mg	Drug: olmesartan medoxomil + amlodipine; One olmesartan medoxomil 20 mg + amlodipine 5 mg combination oral tablet taken once per day; Other Names: Azor
Experimental: olmesartan/amlodipine 40mg/5mg	Drug: olmesartan medoxomil + amlodipine; One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day.
Experimental: olmesartan/amlodipine 40mg/10mg	Drug: olmesartan medoxomil + amlodipine; One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day.; Other Names: Azor

Outcome Measures

Primary Outcome Measures

1. Change in Seated Diastolic Blood Pressure (SeDBP). [Baseline to week 10]

   Baseline blood pressure was defined as the average values obtained at the randomization visit and at the visit prior to randomization

Secondary Outcome Measures

1. Change in Seated Systolic Blood Pressure (SeDBP). [Baseline to week 10]

2. Number of Subjects Reaching Blood Pressure Goal at Week 10 [baseline to week 10]

   Blood pressure treatment goal was defined as blood pressure <140/90 mmHg or <130/80 mmHg for subjects with diabetes, chronic renal disease, or chronic cardiovascular disease.

3. Change in Seated Diastolic Blood Pressure From Week 18 to Week 22 [Week 18 to week 22]

4. Change in Seated Systolic Blood Pressure From Week 18 to Week 22 [Week 18 to week 22]

5. Number of Subjects Reaching Blood Pressure Goal From Week 18 to Week 22 [Week 18 to week 22]

   Blood pressure treatment goal was defined as blood pressure <140/90 mmHg or <130/80 mmHg for subjects with diabetes, chronic renal disease, or chronic cardiovascular disease.

6. Change in Seated Diastolic Blood Pressure From Week 22 to Week 26 [Week 22 to week 26]

7. Change in Seated Systolic Blood Pressure From Week 22 to Week 26 [Week 22 to week 26]

8. Number of Subjects Reaching Blood Pressure Goal at Week 26 [Week 22 to week 26]

   Blood pressure treatment goal was defined as blood pressure <140/90 mmHg or <130/80 mmHg for subjects with diabetes, chronic renal disease, or chronic cardiovascular disease.

9. Change in Seated Systolic Blood Pressure (SeDBP) During Open-Label Period VI (Titration Effect From OM/AML/HCTZ 40/5/25 to 40/10/25. [Week 26 to week 54]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female subjects aged 18 years or older.

• Subjects with mean trough seated blood pressure (SeBP) ≥ 160/100 mmHg, (seated systolic blood pressure(SeSBP) ≥ 160 mmHg and seated diastolic blood pressure (SeDBP) ≥ 100 mmHg) at Screening if not currently on antihypertensive medication (newly diagnosed subjects or subjects who are not taking any antihypertensive medication for at least 3 weeks); Or Subjects with mean trough SeBP ≥ 160/100 mmHg, SeSBP ≥ 160 mmHg and SeDBP ≥ 100 mmHg) after washout of prior antihypertensive medication in subjects who discontinued their previous antihypertensive medication.

The difference in mean SeSBP/SeDBP between the visit prior to randomisation and the randomisation visit must be ≤ 20/10 mmHg. Subjects not currently on antihypertensive (HTN) medication may meet this requirement at the screening visit (Visit 1) and the randomization visit (Visit 3). Subjects washing out of HTN medication must meet this requirement at least by Visit 2 (or Visit 2.1, if needed) and Visit 3. All subjects undergoing washout of their prior antihypertensive medication will have the opportunity to re-visit the study sites for additional visits during washout (Visits 2 and 2.1) to assess eligibility for randomisation.

• Subjects freely sign the informed consent form (ICF) after the nature of the study and the disclosure of his/her data has been explained.

• Female subjects of childbearing potential must be using adequate contraception (female of childbearing potential is defined as one who has not been postmenopausal for at least one year, or has not been surgically sterilised, or has not had a hysterectomy at least three months prior to the start of this study [Visit 1]). Adequate contraceptives include hormonal intra-uterine devices, hormonal contraceptives (oral, depot, patch or injectable), and double barrier methods such as condoms or diaphragms with spermicidal gel or foam.

Exclusion Criteria:

• Female subjects of childbearing potential who are pregnant or lactating.

• Subjects with serious disorders which may limit the ability to evaluate the efficacy or safety of the investigational products, including cerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, haematologic or, neurologic, and psychiatric diseases. The same applies for immunocompromised and/or neutropenic subjects.

• Subjects having a history of the following within the last six months: myocardial infarction (MI), unstable angina pectoris, percutaneous coronary intervention, heart failure, hypertensive encephalopathy, cerebrovascular accident (stroke), or transient ischaemic attack.

• Subjects with clinically significant abnormal laboratory values at Screening, including subjects with one or more of the following:

• Aspartate aminotransferase (AST) > 3 times upper limit of normal (ULN).

• Alanine aminotransferase (ALT) > 3 times ULN.

• Gamma-glutamyl transferase (GGT) > 3 times ULN.

• Potassium above ULN (unless high value is due to haemolytic blood sample).

• Subjects with secondary hypertension of any aetiology such as renal disease, phaeochromocytoma, or Cushing's syndrome.

• Subjects with contraindication to olmesartan, amlodipine, hydrochlorothiazide, or any of the tablet's excipients.

• Newly diagnosed subjects with a mean trough SeSBP > 200 mmHg or mean trough SeDBP > 115 mmHg or any subjects with bradycardia (heart rate < 50 beats/min at rest documented by mean radial pulse rate [PR] or electrocardiogram [ECG]) at Screening (Visit 1) or immediately before taking Period I study medication (Visit 3).

• Subjects already taking four or more antihypertensive medications.

• Subjects with a mean trough SeSBP > 145 mmHg or mean trough SeDBP > 95 mmHg while taking three antihypertensive medications.

• Subjects with a mean trough SeSBP > 160 mmHg or mean trough SeDBP > 100 mmHg while taking two antihypertensive medications.

• Subjects with a mean trough SeSBP > 180 mmHg or mean trough SeDBP > 110 mmHg while taking one antihypertensive medication.

• Subjects with electrocardiogram evidence of 2nd or 3rd degree atrio ventricular (AV) block, atrial fibrillation, or other cardiac arrhythmia (requiring treatment).

• Subjects with severe heart failure (New York Heart Association stage III-IV), clinically significant aortic or mitral valve stenosis, uncorrected coarctation of the aorta, obstruction of cardiac outflow (obstructive, hypertrophic cardiomyopathy) or symptomatic coronary disease.

• Subjects with clinical evidence of renal disease including reno-vascular occlusive disease, nephrectomy and/or renal transplant, bilateral renal artery stenosis, unilateral renal artery stenosis in a solitary kidney, or severe renal impairment as evidenced by CrCl of < 30 mL/min calculated using the Cockcroft and Gault formula.

• Subjects with clinically relevant hepatic impairment.

• Subjects with biliary obstruction.

• Subjects with uncontrolled Type 1 or Type 2 diabetes defined as HbA1c > 9.0%. Diabetics must have documentation of HbA1c within 6 months of the Screening Visit, or must have their HbA1c assessed prior to randomisation. Note: subjects with Type 1 or Type 2 diabetes controlled with insulin, diet or oral hypoglycaemic agents on a stable dose for at least 30 days may be included.

• Subjects with a history of a wasting disease (e.g. cancer), autoimmune diseases, connective tissue diseases, major allergies or angioneurotic oedema.

• Subjects who require or are taking any concomitant medication which may interfere with the objectives of the study.

• Subjects on beta blockers or calcium channel blockers (CCBs) for both hypertension and either ischemia, post-MI prophylaxis or tachyarrhythmias.

• Subjects with known malabsorption syndromes.

• Subjects with psychiatric or emotional problems, which would invalidate the giving of informed consent or limit the ability of the subject to comply with study requirements.

• Subjects with a history of alcohol and/or drug abuse.

• Subjects who have received any investigational agent within 30 days prior to Screening.

• Subjects who are unwilling or unable to provide informed consent or to participate satisfactorily for the entire study.

• Subjects with malignancy during the past 2 years excluding squamous cell or basal cell carcinoma of the skin.

• Subjects with signs or symptoms which could exacerbate the occurrence of hypotension such as volume and salt depletion.

• Subjects with any medical condition, which in the judgment of the Investigator would jeopardise the evaluation of efficacy or safety and/or constitute a significant safety risk to the subject.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Antwerp		Belgium
2		Buizingen		Belgium
3		De Pinte		Belgium
4		Drongen		Belgium
5		Gent		Belgium
6		Gilly		Belgium
7		Merksem		Belgium
8		Mouscron		Belgium
9		Tremelo		Belgium
10		Wichelen		Belgium
11		Burgas		Bulgaria
12		Pleven		Bulgaria
13		Plovdiv		Bulgaria
14		Sofia		Bulgaria
15		Stara Zagora		Bulgaria
16		Veliko Tarnovo		Bulgaria
17		Benatky nad Jizerou		Czechia
18		Brodce		Czechia
19		Havirov		Czechia
20		Jicin		Czechia
21		Mlada Boleslav		Czechia
22		Moravska Ostrava		Czechia
23		Plzen		Czechia
24		Prachatice		Czechia
25		Praha		Czechia
26		Sokolov		Czechia
27		Copenhagen		Denmark
28		Frederiksberg		Denmark
29		Roskilde		Denmark
30		Berlin		Germany
31		Cloppenburg		Germany
32		Delitzsch		Germany
33		Dresden		Germany
34		Erfurt		Germany
35		Essen		Germany
36		Hamburg		Germany
37		Heidelberg		Germany
38		Leipzig		Germany
39		Northeim		Germany
40		Simmern		Germany
41		Wallerfing		Germany
42		Wiesbaden		Germany
43		Budapest		Hungary
44		Debrecen		Hungary
45		Hodmezovasarhely		Hungary
46		Jaszbereny		Hungary
47		Kaposvar		Hungary
48		Kecskemet		Hungary
49		Oroshaza		Hungary
50		Pecs		Hungary
51		Szekesfehervar		Hungary
52		Veszprem		Hungary
53		Zalaegerszeg		Hungary
54		Bologna		Italy
55		Brescia		Italy
56		Chieti		Italy
57		Ferrara		Italy
58		Foggia		Italy
59		Genova		Italy
60		Palermo		Italy
61		Parma		Italy
62		Perugia		Italy
63		Pisa		Italy
64		Roma		Italy
65		Sassari		Italy
66		Stradella Pavia		Italy
67		Cesis		Latvia
68		Daugavpils		Latvia
69		Jekabpils		Latvia
70		Ogre		Latvia
71		Riga		Latvia
72		Tukums		Latvia
73		Varaklani		Latvia
74		Ventspils		Latvia
75		Deurne		Netherlands
76		Eindhoven		Netherlands
77		Lichtenvoorde		Netherlands
78		Lieshout		Netherlands
79		Rotterdam		Netherlands
80		Utrecht		Netherlands
81		Bialystok		Poland
82		Debica		Poland
83		Gdansk		Poland
84		Gdynia		Poland
85		Jastrzebia Zdroj		Poland
86		Krakow		Poland
87		Lublin		Poland
88		Mielec		Poland
89		Opole		Poland
90		Szczecin		Poland
91		Warsaw		Poland
92		Wroclaw		Poland
93		Arad		Romania
94		Bucharest		Romania
95		Craiova		Romania
96		Iasi		Romania
97		Pitesti		Romania
98		Ploiesti		Romania
99		Sibiu		Romania
100		Suceava		Romania
101		Timisoara		Romania
102		Barnaul		Russian Federation
103		Moscow		Russian Federation
104		Novosibirsk		Russian Federation
105		Saint Petersburg		Russian Federation
106		Tyumen		Russian Federation
107		Yaroslavl		Russian Federation
108		Banska Bysterica		Slovakia
109		Bratilslava		Slovakia
110		Nitra		Slovakia
111		Povazska Bystrica		Slovakia
112		Rimavska Sobota		Slovakia
113		Zilina		Slovakia
114		Badalona		Spain
115		Barcelona		Spain
116		Ferrol		Spain
117		Lleida		Spain
118		Madrid		Spain
119		Petrer		Spain
120		Salamanca		Spain
121		Santiago de Compostela		Spain
122		Valencia		Spain
123		Dnipropetrovsk		Ukraine
124		Donetsk		Ukraine
125		Kharkiv		Ukraine
126		Kyiv		Ukraine
127		Lutsk		Ukraine
128		Lviv		Ukraine
129		Odesa		Ukraine
130		Simferopol		Ukraine
131		Vinnytsya		Ukraine
132		Zaporizhzhya		Ukraine
133		Zhytomyr		Ukraine

Sponsors and Collaborators

• Daiichi Sankyo, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT00923091
• Other Study ID Numbers: CS8635-A-E302
• First Posted: Jun 18, 2009
• Last Update Posted: Jan 10, 2019
• Last Verified: Apr 1, 2012

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Daiichi Sankyo, Inc.: triple combination; parallel group; dual combination
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Amlodipine; Hydrochlorothiazide; Olmesartan; Olmesartan Medoxomil; Amlodipine Besylate, Olmesartan Medoxomil Drug Combination

Study Results

Participant Flow

Recruitment Details	This study was conduct in Europe from 27 May 2009 to 12 January 2011
Pre-assignment Detail	Study has randomised, double-blind, placebo-controlled parallel-group portion (Periods I-II) followed by transition phase (Periods III-V) wherein combination titration steps were evaluated in subjects not achieving blood pressure goals. The transition required that all be entered into Period 3 on olm/aml/hctz 20/5/12.5 to ensure a common baseline.

Arm/Group Title	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg	Olmesartan/Amlodipine/Hydrochlorothiazide(HCT) 40mg/10mg/25mg	Olmesartan(OM)20mg/Amlodipine (AML)5mg	Olmesartan/Amlodipine 40mg/5mg	Olmesartan/Amlodipine 40mg/10mg	OM/AML/HCT 40/5/12.5mg Responder Continued on 40/5/12.5 mg	OM/AML/HCT 40/5/12.5mg Non Responder Randomized to 40/5/12.5mg	OM/AML/HCT 40/5/12.5mg Non Responder Randomized to 40/5/25mg	OM/AML/HCT 20/5/12.5mg NonResponder Up Titrated to 40/5/12.5mg	20/5/12.5mg Responder Continued on 20/5/12.5 mg
Arm/Group Description	Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion. In Period III, all participants were included in this group. Responders (a participant was considered a responder if their blood pressure was <140/90 mm Hg; <130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease) in Period III went directly to Period VI. In Period IV participants who did not meet the blood pressure goals in Period III were randomized in a 1:2 fashion to this group or the OLM/AML/HCTZ 40/5/12.5 group.	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion. In Period IV participants who did not meet the blood pressure goals (<140/90 mm Hg; or <130/80 for participants with diabetes or chronic renal or cardiovascular disease)in Period III were randomized in a 1:2 fashion to OLM/AML/HCTZ 20/5/12.5 or this group.	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	In Period V responders continued on olmesartan/amlodipine/ hydrochlorothiazide 40mg/5mg/12.5 mg. A participant was considered a responder if their blood pressure was <140/90 mm Hg; <130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.	In Period V OLM/AML/HCTZ 40/5/12.5 non-responders were randomized to olmesartan/amlodipine/hydrochlorothiazide 40mg/5mg/12.5 mg or to 40mg/5mg/25 mg. A participant was considered a responder if their blood pressure was <140/90 mm Hg; <130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.	In Period V OLM/AML/HCTZ 40/5/12.5 non-responders were randomized to olmesartan/amlodipine/hydrochlorothiazide 40mg/5mg/12.5 mg or to 40mg/5mg/25 mg. A participant was considered a responder if their blood pressure was <140/90 mm Hg; <130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.	In Period V non-responders to olmesartan/amlodipine/hydrochlorothiazide 20mg/5mg/12.5 mg were up titrated to 40mg/5mg/12.5mg. A participant was considered a responder if their blood pressure was <140/90 mm Hg; <130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.	In Period V non-responders to olmesartan/amlodipine/hydrochlorothiazide 20mg/5mg/12.5 mg continued on 20mg/5mg/12.5mg. A participant was considered a responder if their blood pressure was <140/90 mm Hg; <130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.
Period Title: PeriodI-II (Randomized, Double-Blind)
STARTED	335	336	336	336	336	337	337	336	0	0	0	0	0
COMPLETED	319	325	323	309	315	322	319	311	0	0	0	0	0
NOT COMPLETED	16	11	13	27	21	15	18	25	0	0	0	0	0
Period Title: PeriodI-II (Randomized, Double-Blind)
STARTED	2540	0	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	2520	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	20	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: PeriodI-II (Randomized, Double-Blind)
STARTED	228	453	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	226	451	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	2	2	0	0	0	0	0	0	0	0	0	0	0
Period Title: PeriodI-II (Randomized, Double-Blind)
STARTED	0	0	0	0	0	0	0	0	135	119	194	151	75
COMPLETED	0	0	0	0	0	0	0	0	134	119	193	151	73
NOT COMPLETED	0	0	0	0	0	0	0	0	1	0	1	0	2
Period Title: PeriodI-II (Randomized, Double-Blind)
STARTED	1447	272	480	146	164	0	0	0	0	0	0	0	0
COMPLETED	1408	264	467	143	157	0	0	0	0	0	0	0	0
NOT COMPLETED	39	8	13	3	7	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg	Olmesartan/Amlodipine 20mg/5mg	Olmesartan/Amlodipine 40mg/5mg	Olmesartan/Amlodipine 40mg/10mg	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	335	336	336	336	336	337	337	336	2689
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.0 (10.81)	56.8 (10.36)	56.5 (10.92)	57.0 (10.72)	55.9 (11.08)	56.1 (10.22)	56.4 (10.4)	57.0 (9.70)	56.5 (10.53)
Sex: Female, Male (Count of Participants)
Female	182 54.3%	171 50.9%	184 54.8%	181 53.9%	178 53%	185 54.9%	170 50.4%	192 57.1%	1443 53.7%
Male	153 45.7%	165 49.1%	152 45.2%	155 46.1%	158 47%	152 45.1%	167 49.6%	144 42.9%	1246 46.3%
Race/Ethnicity, Customized (Number) [Number]
Asian	1 0.3%	0 0%	1 0.3%	0 0%	0 0%	0 0%	0 0%	1 0.3%	3 0.1%
Black	0 0%	0 0%	0 0%	1 0.3%	0 0%	0 0%	0 0%	0 0%	1 0%
White	334 99.7%	336 100%	335 99.7%	335 99.7%	336 100%	337 100%	337 100%	335 99.7%	2685 99.9%
Region of Enrollment (Number) [Number]
Europe	335 100%	336 100%	336 100%	336 100%	336 100%	337 100%	337 100%	336 100%	2689 100%

Outcome Measures

1. Primary Outcome

Title	Change in Seated Diastolic Blood Pressure (SeDBP).
Description	Baseline blood pressure was defined as the average values obtained at the randomization visit and at the visit prior to randomization
Time Frame	Baseline to week 10

Outcome Measure Data

Analysis Population Description

The full analysis set includes 2679 randomized patients who received at least 1 dose of double-blind medication and who provided at least one diastolic blood pressure measurement in Period I-II

Arm/Group Title	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg	Olmesartan/Amlodipine 20mg/5mg	Olmesartan/Amlodipine 40mg/5mg	Olmesartan/Amlodipine 40mg/10mg
Arm/Group Description	Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Measure Participants	334	336	335	336	332	337	334	335
Least Squares Mean (Standard Error) [mm HG]	-22.5 (0.48)	-22.5 (0.48)	-23.0 (0.48)	-23.9 (0.47)	-23.8 (0.48)	-20.5 (0.47)	-21.2 (0.48)	-22.1 (0.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg, Olmesartan/Amlodipine 20mg/5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0071
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg, Olmesartan/Amlodipine 40mg/5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0323
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg, Olmesartan/Amlodipine 40mg/5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0080
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg, Olmesartan/Amlodipine 40mg/10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0071
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg, Olmesartan/Amlodipine 40mg/10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0107
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Change in Seated Systolic Blood Pressure (SeDBP).
Time Frame	Baseline to week 10

Outcome Measure Data

Analysis Population Description

The full analysis set includes 2679 randomized patients who received at least 1 dose of double-blind medication and who provided at least one diastolic blood pressure measurement in Period I-II

Arm/Group Title	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg	Olmesartan/Amlodipine 20mg/5mg	Olmesartan/Amlodipine 40mg/5mg	Olmesartan/Amlodipine 40mg/10mg
Arm/Group Description	Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Measure Participants	334	336	335	336	332	337	334	335
Least Squares Mean (Standard Error) [mm Hg]	-33.2 (0.72)	-33.7 (0.72)	-35.3 (0.71)	-35.5 (0.71)	-36.2 (0.72)	-29.9 (0.71)	-30.4 (0.71)	-32.8 (0.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg, Olmesartan/Amlodipine 20mg/5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg, Olmesartan/Amlodipine 40mg/5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg, Olmesartan/Amlodipine 40mg/5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg, Olmesartan/Amlodipine 40mg/10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0034
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg, Olmesartan/Amlodipine 40mg/10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Number of Subjects Reaching Blood Pressure Goal at Week 10
Description	Blood pressure treatment goal was defined as blood pressure <140/90 mmHg or <130/80 mmHg for subjects with diabetes, chronic renal disease, or chronic cardiovascular disease.
Time Frame	baseline to week 10

Outcome Measure Data

Analysis Population Description

The full analysis set includes 2679 randomized patients who received at least 1 dose of double-blind medication and who provided at least one diastolic blood pressure measurement in Period I-II

Arm/Group Title	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg	Olmesartan/Amlodipine 20mg/5mg	Olmesartan/Amlodipine 40mg/5mg	Olmesartan/Amlodipine 40mg/10mg
Arm/Group Description	Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Measure Participants	334	336	335	336	332	337	334	335
Number [Participants]	177 52.8%	176 52.4%	197 58.6%	190 56.5%	179 53.3%	144 42.7%	155 46%	166 49.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg, Olmesartan/Amlodipine 20mg/5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0295
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg, Olmesartan/Amlodipine 40mg/5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2529
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg, Olmesartan/Amlodipine 40mg/5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0037
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg, Olmesartan/Amlodipine 40mg/10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2033
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg, Olmesartan/Amlodipine 40mg/10mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2529
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

4. Secondary Outcome

Title	Change in Seated Diastolic Blood Pressure From Week 18 to Week 22
Time Frame	Week 18 to week 22

Outcome Measure Data

Analysis Population Description

The Full Analysis Set 2=681 randomized participants who received at least 1 dose of double-blind medication and who provided at least one diastolic blood pressure measurement in Period IV

Arm/Group Title	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg
Arm/Group Description	Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg. hydrochlorothiazide placebo tablet. Participants from Period III who did not meet blood pressure goals (<140/90; 130/80 for participants with diabetes, chronic renal disease, or chronic cardiovascular disease)were randomized to Period IV in a 1:2 ratio to continue olm/aml/hctz 20/5/12.5 or be up-titrated to olm/aml/hctz 40/5/12.5.	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet. Participants from Period III who did not meet blood pressure goals (<140/90; 130/80 for participants with diabetes, chronic renal disease, or chronic cardiovascular disease)were randomized to Period IV in a 1:2 ratio to continue olm/aml/hctz 20/5/12.5 or be up-titrated to olm/aml/hctz 40/5/12.5.
Measure Participants	228	453
Least Squares Mean (Standard Error) [mm Hg]	-3.3 (0.47)	-4.1 (0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg, Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1135
	Comments
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Change in Seated Systolic Blood Pressure From Week 18 to Week 22
Time Frame	Week 18 to week 22

Outcome Measure Data

Analysis Population Description

The Full Analysis Set 2=681 randomized participants who received at least 1 dose of double-blind medication and who provided at least one blood pressure measurement in Period IV

Arm/Group Title	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg
Arm/Group Description	Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg. hydrochlorothiazide placebo tablet. Participants from Period III who did not meet blood pressure goals (<140/90; 130/80 for participants with diabetes, chronic renal disease, or chronic cardiovascular disease)were randomized to Period IV in a 1:2 ratio to continue olm/aml/hctz 20/5/12.5 or be up-titrated to olm/aml/hctz 40/5/12.5.	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg. hydrochlorothiazide placebo tablet. Participants from Period III who did not meet blood pressure goals (<140/90; 130/80 for participants with diabetes, chronic renal disease, or chronic cardiovascular disease)were randomized to Period IV in a 1:2 ratio to continue olm/aml/hctz 20/5/12.5 or be up-titrated to olm/aml/hctz 40/5/12.5.
Measure Participants	228	453
Least Squares Mean (Standard Error) [mm Hg]	-5.7 (0.71)	-6.5 (0.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg, Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2765
	Comments
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Number of Subjects Reaching Blood Pressure Goal From Week 18 to Week 22
Description	Blood pressure treatment goal was defined as blood pressure <140/90 mmHg or <130/80 mmHg for subjects with diabetes, chronic renal disease, or chronic cardiovascular disease.
Time Frame	Week 18 to week 22

Outcome Measure Data

Analysis Population Description

The Full Analysis Set 2=681 randomized participants who received at least 1 dose of double-blind medication and who provided at least one diastolic blood pressure measurement in Period IV

Arm/Group Title	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg
Arm/Group Description	Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg. hydrochlorothiazide placebo tablet. Participants from Period III who did not meet blood pressure goals (<140/90; 130/80 for participants with diabetes, chronic renal disease, or chronic cardiovascular disease)were randomized to Period IV in a 1:2 ratio to continue olm/aml/hctz 20/5/12.5 or be up-titrated to olm/aml/hctz 40/5/12.5.	Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg. hydrochlorothiazide placebo tablet. Participants from Period III who did not meet blood pressure goals (<140/90; 130/80 for participants with diabetes, chronic renal disease, or chronic cardiovascular disease)were randomized to Period IV in a 1:2 ratio to continue olm/aml/hctz 20/5/12.5 or be up-titrated to olm/aml/hctz 40/5/12.5.
Measure Participants	228	453
Number [Participants]	63 18.8%	137 40.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg, Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4964
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

7. Secondary Outcome

Title	Change in Seated Diastolic Blood Pressure From Week 22 to Week 26
Time Frame	Week 22 to week 26

Outcome Measure Data

Analysis Population Description

The Full Analysis Set 3=312 randomized participants who received at least one dose of double-blind medication and who provided at least one diastolic blood pressure measurement in Period V.

Arm/Group Title	OLM/AML/HCTZ 40/5/12.5mg Nonresponders Randomized to 40/5/12.5	OLM/AML/HCTZ 40/5/12.5mg Nonresponders Randomized to 40/5/25
Arm/Group Description	This arm contain participants who did not responded to olmesartan\amlodipine\hydrochlorothiazide 40/5/12.5 and who were randomized to that combination in Period V	This arm contain participants who did not respond to olmesartan\amlodipine\hydrochlorothiazide 40/5/12.5 and who were randomized to 40/5/25 in Period V
Measure Participants	119	193
Least Squares Mean (Standard Error) [mm Hg]	-2.7 (0.68)	-3.8 (0.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg, Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1301
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg, Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01301
	Comments
	Method	ANCOVA
	Comments

8. Secondary Outcome

Title	Change in Seated Systolic Blood Pressure From Week 22 to Week 26
Time Frame	Week 22 to week 26

Outcome Measure Data

Analysis Population Description

The Full Analysis Set 3=312 randomized participants who received at least one dose of double-blind medication and who provided at least one diastolic blood pressure measurement in Period V.

Arm/Group Title	OLM/AML/HCTZ 40/5/12.5mg Nonresponders Randomized to 40/5/12.5	OLM/AML/HCTZ40/5/12.5mg Nonresponders Randomized to 40/5/25
Arm/Group Description	This arm contain participants who did not responded to olmesartan\amlodipine\hydrochlorothiazide 40/5/12.5 and who were randomized to that combination in Period V	This arm contain participants who did not respond to olmesartan\amlodipine\hydrochlorothiazide 40/5/12.5 and who were randomized to 40/5/25 in Period V
Measure Participants	119	193
Least Squares Mean (Standard Error) [mm Hg]	-4.5 (1.01)	-6.7 (0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg, Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0503
	Comments
	Method	ANCOVA
	Comments

9. Secondary Outcome

Title	Number of Subjects Reaching Blood Pressure Goal at Week 26
Description	Blood pressure treatment goal was defined as blood pressure <140/90 mmHg or <130/80 mmHg for subjects with diabetes, chronic renal disease, or chronic cardiovascular disease.
Time Frame	Week 22 to week 26

Outcome Measure Data

Analysis Population Description

The Full Analysis Set 3=312 randomized participants who received at least one dose of double-blind medication and who provided at least one diastolic blood pressure measurement in Period V

Arm/Group Title	OLM/AML/HCTZ 40/5/12.5mg Nonresponders Randomized to 40/5/12.5	OLM/AML/HCTZ 40/5/12.5mg Nonresponders Randomized to 40/5/25
Arm/Group Description	This arm contain participants who did not responded to olmesartan\amlodipine\hydrochlorothiazide 40/5/12.5 and who were randomized to that combination in Period V	This arm contain participants who did not respond to olmesartan\amlodipine\hydrochlorothiazide 40/5/12.5 and who were randomized to 40/5/25 in Period V
Measure Participants	119	193
Number [Participants]	29 8.7%	47 14%

10. Secondary Outcome

Title	Change in Seated Systolic Blood Pressure (SeDBP) During Open-Label Period VI (Titration Effect From OM/AML/HCTZ 40/5/25 to 40/10/25.
Time Frame	Week 26 to week 54

Outcome Measure Data

Analysis Population Description

The number of subjects up titrated who had blood pressure values at both time points.

Arm/Group Title	OLM/AML/HCTZ 40/5/25 Titrated to 40/10/25
Arm/Group Description	The participants in this arm had their study medication titrated from olmesartan\amlodipine\hydrochlorothiazide 40/5/25 to 40/10/25
Measure Participants	87
Mean (Standard Deviation) [mm Hg]	-11.9 (11.01)

Adverse Events

Time Frame	Week 1 to week 54
Adverse Event Reporting Description	All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Arm/Group Title	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg		Olmesartan/Amlodipine 20mg/5mg		Olmesartan/Amlodipine 40mg/5mg		Olmesartan/Amlodipine 40mg/10mg
Arm/Group Description
All Cause Mortality
	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg		Olmesartan/Amlodipine 20mg/5mg		Olmesartan/Amlodipine 40mg/5mg		Olmesartan/Amlodipine 40mg/10mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg		Olmesartan/Amlodipine 20mg/5mg		Olmesartan/Amlodipine 40mg/5mg		Olmesartan/Amlodipine 40mg/10mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/329 (16.7%)		9/334 (2.7%)		22/331 (6.6%)		3/329 (0.9%)		7/332 (2.1%)		1/333 (0.3%)		5/332 (1.5%)		7/325 (2.2%)
Cardiac disorders
Tachycardia paroxysmal	0/329 (0%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		1/332 (0.3%)		0/325 (0%)
Acute myocardial infarction	0/329 (0%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		1/332 (0.3%)		0/333 (0%)		1/332 (0.3%)		0/325 (0%)
Atrial fibrillation	2/329 (0.6%)		1/334 (0.3%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		1/325 (0.3%)
Angina unstable	2/329 (0.6%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		1/325 (0.3%)
Left ventricular failure	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Myocardial infarction	1/329 (0.3%)		0/334 (0%)		2/331 (0.6%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Cardiogenic shock	1/329 (0.3%)		1/334 (0.3%)		1/331 (0.3%)		1/329 (0.3%)		1/332 (0.3%)		1/333 (0.3%)		1/332 (0.3%)		1/325 (0.3%)
Angina pectoris	1/329 (0.3%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Coronary artery disease	0/329 (0%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Acute coronary syndrome	0/329 (0%)		0/334 (0%)		0/331 (0%)		1/329 (0.3%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Extrasystoles	0/329 (0%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/0 (NaN)		0/325 (0%)
Eye disorders
Angle closure glaucoma	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Cataract	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Eye haemorrhage	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Retinal Detachment	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Ulcerative keratitis	0/329 (0%)		1/334 (0.3%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Gastrointestinal disorders
Inguinal hernia	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		1/332 (0.3%)		0/325 (0%)
Oesophagitis	0/329 (0%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		1/325 (0.3%)
Gastric Polyps	0/329 (0%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		1/332 (0.3%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Pancreatitis chronic	1/329 (0.3%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Colonic polyp	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Gastritis	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Mouth cyst	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Ascites	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Hepatobiliary disorders
Cholecystitis	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Infections and infestations
Bronchopneumonia	0/329 (0%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		1/332 (0.3%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Pneumonia	1/329 (0.3%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Sinusitis	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Mediastinitis	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Pyothorax	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Peritonsillar abcess	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Appendicitis	0/329 (0%)		0/334 (0%)		0/331 (0%)		1/329 (0.3%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Injury, poisoning and procedural complications
Meniscus lesion	0/329 (0%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		1/325 (0.3%)
Tendon rupture	2/329 (0.6%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Tibia fracture	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Ankle fracture	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Barotrauma	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Tendon injury	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Intentional overdose	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Patella fracture	0/329 (0%)		1/334 (0.3%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Vertebral injury	0/329 (0%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Femeral Neck Fracture	0/329 (0%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Investigations
Electrocardiogram QRS complex shortened	0/329 (0%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		1/332 (0.3%)		0/325 (0%)
Hepatitus B virus	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Blood pressure decreased	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Metabolism and nutrition disorders
Hypokalemia	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Diabetes mellitus	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/329 (0%)		0/334 (0%)		4/331 (1.2%)		0/329 (0%)		1/332 (0.3%)		0/333 (0%)		0/332 (0%)		1/325 (0.3%)
Torticollis	0/329 (0%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Back pain	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Musculoskeletal pain	0/329 (0%)		1/334 (0.3%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Spinal osteoarthritis	0/329 (0%)		1/334 (0.3%)		0/331 (0%)		0/329 (0%)		1/332 (0.3%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Transitional cell carcinoma	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Ovarian cancer	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Malignant fibrous histiocytoma	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Prostatic adenoma	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Prostate cancer	0/329 (0%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Uterine leiomyoma	0/329 (0%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		1/325 (0.3%)
Nervous system disorders
Transient ischemic attack	0/329 (0%)		1/334 (0.3%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Ischaemic stroke	2/329 (0.6%)		2/334 (0.6%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Syncope	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Dizziness	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Cerebral ischaemia	0/329 (0%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Psychiatric disorders
Completed suicide	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Alcohol abuse	0/329 (0%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		1/332 (0.3%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Renal and urinary disorders
Calculus ureteric	0/329 (0%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Hydronephrosis	0/329 (0%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Reproductive system and breast disorders
Uterine polyp	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Benign prostatic hyperplasia	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Prostatitis	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/329 (0.3%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Surgical and medical procedures
Removal of internal fixation	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Vascular disorders
Hypertension	2/329 (0.6%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Arterial thrombosis limb	1/329 (0.3%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Hypertensive crisis	1/329 (0.3%)		0/334 (0%)		1/331 (0.3%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		0/332 (0%)		0/325 (0%)
Other (Not Including Serious) Adverse Events
	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg		Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg		Olmesartan/Amlodipine 20mg/5mg		Olmesartan/Amlodipine 40mg/5mg		Olmesartan/Amlodipine 40mg/10mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/329 (3.6%)		44/334 (13.2%)		13/331 (3.9%)		39/329 (11.9%)		45/332 (13.6%)		26/333 (7.8%)		38/332 (11.4%)		30/325 (9.2%)
General disorders
Oedema peripheral	0/329 (0%)		15/334 (4.5%)		0/331 (0%)		26/329 (7.9%)		27/332 (8.1%)		11/333 (3.3%)		16/332 (4.8%)		30/325 (9.2%)
Investigations
Nasopharyngitis	0/329 (0%)		13/334 (3.9%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		11/332 (3.3%)		0/325 (0%)
Metabolism and nutrition disorders
Dyslipidaemia	0/329 (0%)		0/334 (0%)		0/331 (0%)		0/329 (0%)		0/332 (0%)		0/333 (0%)		11/332 (3.3%)		0/325 (0%)
Nervous system disorders
Headache	12/329 (3.6%)		16/334 (4.8%)		13/331 (3.9%)		13/329 (4%)		18/332 (5.4%)		15/333 (4.5%)		0/332 (0%)		0/325 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A site may not publish results until after a coordinated multicentre publication has been submitted for publication or until one year after the study has ended, whichever occurs first. Then, the site will have the opportunity to publish the results, provided that DSE has had the opportunity to review and comment on the site's proposed publication prior to its being submitted for publication with the advice of company patent council and in accord with needs for subject protection.