Blood Pressure Lowering Ability and Safety of an Olmesartan and Amlodipine Based Treatment Regimen in Patients With Stage I and Stage II Hypertension

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00527514
• Collaborator: (none)
• Enrollment: 185
• Locations: 18
• Arm: 1
• Duration (Months): 7
• Patients Per Site: 10.3
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

This study will be conducted to assess the efficacy and safety of an amlodipine/olmesartan treatment regimen in stage 1 and stage 2 hypertensive subjects.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Amlodipine; Drug: Olmesartan medoxomil plus amlodipine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 185 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Open-label Study to Assess the Efficacy and Safety of an Olmesartan and Amlodipine Based Treatment Regimen in Subjects With Stage 1 and Stage 2 Hypertension
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Amlodipine; Tablets; Drug: Olmesartan medoxomil plus amlodipine; Tablets

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Mean 24-hour Systolic Blood Pressure Measured by Ambulatory Monitoring [Baseline to 12 Weeks]

Secondary Outcome Measures

1. Change From Baseline in Daytime and Nighttime Ambulatory Systolic Blood Pressure [Baseline to 12 weeks]

2. Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg Group. [Baseline to end of week 3]

   Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis.

3. Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg + Olmesartan 20 mg Group. [Baseline to end of week 6]

   Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis.

4. Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg + Olmesartan 40 mg Group [Baseline to end of week 9]

   Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis.

5. Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 10 mg + Olmesartan 40 mg Group [Baseline to end end of week 12]

   Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Males or females greater than or equal to 18 years of age

• Patients with a mean seated systolic blood pressure (MSSBP) greater than or equal to 140 mm Hg but less than or equal to 199 mm Hg or a mean seated diastolic blood pressure (MSDBP) greater than or equal to 90 mm Hg and less than or equal to 109 mm Hg, following a period of taking only placebo

• Patients with a mean daytime (8AM-4PM) systolic blood pressure greater than or equal to 135 mm Hg and less than or equal to 199 mm Hg and a mean daytime diastolic blood pressure less than or equal to 109 mm Hg as measured by an ambulatory blood pressure monitoring device (ABPM), after a period of taking only placebo

• If female, must have negative serum pregnancy test at screening and be either post-menopausal (greater than or equal to 1 year), had a hysterectomy or tubal ligation at least 6 months before consent or if of childbearing potential, must practice approved measures of birth control throughout study

Exclusion Criteria:

• History of stroke or transient ischemic attack (TIA) within the last one year

• History of myocardial infarction, coronary angioplasty, coronary artery bypass graft, or heart failure within the past 6 months

• Patients with secondary hypertension of any etiology, such as renal disease, pheochromocytoma, or Cushing's syndrome

• Type I diabetes. Patients with Type II diabetes on stable treatment, with fasting glucose <160 mg/dl may enroll

• Patients with hemodynamically significant cardiac valvular disease

• Patients with clinically significant cardiac conduction defects, including second or third degree AV block, left bundle branch block, sick sinus syndrome, atrial fibrillation, atrial flutter, an accessory bypass tract, or any arrhythmia requiring medication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Buena Park	California	United States
2		Long Beach	California	United States
3		Los Angeles	California	United States
4		Sacramento	California	United States
5		Tustin	California	United States
6		Westlake Village	California	United States
7		Castle Rock	Colorado	United States
8		Pembroke Pines	Florida	United States
9		Orland Park	Illinois	United States
10		Natick	Massachusetts	United States
11		New York	New York	United States
12		Winston-Salem	North Carolina	United States
13		Cincinnati	Ohio	United States
14		Beaver	Pennsylvania	United States
15		Greer	South Carolina	United States
16		Carrolton	Texas	United States
17		Corpus Christi	Texas	United States
18		Madison	Wisconsin	United States

Sponsors and Collaborators

• Daiichi Sankyo, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00527514
• Other Study ID Numbers: 8663-402
• First Posted: Sep 11, 2007
• Last Update Posted: Nov 11, 2009
• Last Verified: Nov 1, 2009

• Keywords provided by , ,: Hypertension; Angiotensin Receptor Blocker; Calcium Channel Blocker; Stage I and II Hypertension
• Additional relevant MeSH terms: Hypertension; Amlodipine; Olmesartan; Olmesartan Medoxomil

Study Results

Participant Flow

Recruitment Details	Participants were recruited at 18 US sites over 4 months (September 2007 to December 2007) from each physician's clientele base. Approximately 150 eligible participants, men and women at least 18 years of age with hypertension or uncontrolled hypertension on current medication, were to receive active treatment
Pre-assignment Detail	After placebo treatment, participants with a mean systolic blood pressure (SBP)≥140 mmHg and ≤199 mmHg or a mean diastolic BP (DBP)≥90 and ≤109 mmHg with a difference between mean SBPs ≤15 mmHg and a mean 8-hr daytime SBP of ≥135 mmHg and ≤199 mmHg, and mean 8-hr daytime DBP of <110 mmHg by ambulatory BP monitoring were considered eligible.

Arm/Group Title	Amlodipine and Olmesartan, if Necessary
Arm/Group Description	All eligible participants began the active treatment period with amlodipine (Aml) 5 mg for Weeks 1-3. If blood pressure was greater than 120/80 at the end of 3 weeks, participants were titrated to the next regimen for weeks 4-6, and so on for weeks 7-9 and 10-12.
Period Title: Weeks 1-3: Amlodipine (Aml) 5mg
STARTED	185
COMPLETED	184
NOT COMPLETED	1
Period Title: Weeks 1-3: Amlodipine (Aml) 5mg
STARTED	180
COMPLETED	178
NOT COMPLETED	2
Period Title: Weeks 1-3: Amlodipine (Aml) 5mg
STARTED	161
COMPLETED	158
NOT COMPLETED	3
Period Title: Weeks 1-3: Amlodipine (Aml) 5mg
STARTED	134
COMPLETED	132
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Amlodipine and Olmesartan, if Necessary
Arm/Group Description	Week 1-3 all participants: Amlodipine 5mg; Week 4-6 Amlodipine 5 mg/olmesartan 20 mg if mean SBP >= 120/80 mm Hg; Week 7-9 Amlodipine 5 mg/ olmesartan 40 mg if mean SBP >= 120/80 mm Hg; Week 10-12 Amlodipine 10 mg/olmesartan 40 mg if mean SBP >= 120/80 mm Hg
Overall Participants	185
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.8 (9.28)
Sex: Female, Male (Count of Participants)
Female	80 43.2%
Male	105 56.8%
Race/Ethnicity, Customized (Number) [Number]
Asian	14 7.6%
Black or African American	26 14.1%
White	144 77.8%
American Indian or Alaska Native	1 0.5%
Region of Enrollment (participants) [Number]
United States	185 100%
Stage of Hypertension (Number) [Number]
Stage 1	82 44.3%
Stage 2	103 55.7%
24-Hour Ambulatory Diastolic Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	85.8 (7.91)
24-hour Ambulatory Systolic Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	144.6 (10.88)
Heart Rate (beats/minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats/minute]	75.1 (10.82)
Systolic Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	158.2 (12.63)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Mean 24-hour Systolic Blood Pressure Measured by Ambulatory Monitoring
Time Frame	Baseline to 12 Weeks

Outcome Measure Data

Analysis Population Description

The ambulatory blood pressure monitoring (ABPM) subset were subjects who received at least one dose of active study medication and had a baseline ABPM and end of study ABPM measurement.This = 172 participants.

Arm/Group Title	Overall Active Treatment Period
Arm/Group Description
Measure Participants	172
Mean (Standard Deviation) [mm Hg]	-21.4 (0.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Overall Active Treatment Period
	Comments	The sample size of this study was not based on the statistical power consideration and was considered as sufficient for the evaluation of the efficacy and safety of the proposed olmesartan medoxomil-based treatment regimen.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No multiplicity adjustments
	Method	one-sample t-test
	Comments

2. Secondary Outcome

Title	Change From Baseline in Daytime and Nighttime Ambulatory Systolic Blood Pressure
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

The ambulatory blood pressure monitoring (ABPM) subset were subjects who received at least one dose of active study medication and had a baseline ABPM and end of study ABPM measurement.This = 172 participants.

Arm/Group Title	Overall Active Treatment Period
Arm/Group Description
Measure Participants	172
Daytime	-23.1 (0.92)
Nighttime	-18.5 (0.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Overall Active Treatment Period
	Comments	Statistical analysis parameters apply to both the daytime and nighttime rows.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No multiplicity adjustments
	Method	One-sample t-test
	Comments

3. Secondary Outcome

Title	Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg Group.
Description	Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis.
Time Frame	Baseline to end of week 3

Outcome Measure Data

Analysis Population Description

ITT (efficacy cohort)

Arm/Group Title	Group 1 Amlodipine 5 mg
Arm/Group Description	All participants started the Active Treatment period with 5 mg of amlodipine for 3 weeks.
Measure Participants	185
Mean (Standard Deviation) [mm Hg]	-10.1 (0.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Overall Active Treatment Period
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No multiplicity adjustments
	Method	One-sample t-test
	Comments

4. Secondary Outcome

Title	Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg + Olmesartan 20 mg Group.
Description	Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis.
Time Frame	Baseline to end of week 6

Outcome Measure Data

Analysis Population Description

ITT (efficacy cohort)

Arm/Group Title	Group 2 - Aml 5 mg + Olmesartan 20 mg
Arm/Group Description	Participants from Group 1 who did not meet the blood pressure goal after 3 weeks were titrated to Aml 5 mg + olmesartan 20 mg.
Measure Participants	179
Mean (Standard Error) [mm Hg]	-18.0 (0.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Overall Active Treatment Period
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No multiplicity adjustments
	Method	one-sample t-test
	Comments

5. Secondary Outcome

Title	Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg + Olmesartan 40 mg Group
Description	Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis.
Time Frame	Baseline to end of week 9

Outcome Measure Data

Analysis Population Description

ITT (efficacy cohort)

Arm/Group Title	Group 3 - Aml 5 mg + Olm 40 mg
Arm/Group Description	Participants from Group 2 who did not meet the blood pressure goal after 3 weeks were titrated to Aml 5 mg + olmesartan 40mg.
Measure Participants	160
Mean (Standard Error) [mm Hg]	-20.5 (1.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Overall Active Treatment Period
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No multiplicity adjustments
	Method	One-sample t-test
	Comments

6. Secondary Outcome

Title	Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 10 mg + Olmesartan 40 mg Group
Description	Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis.
Time Frame	Baseline to end end of week 12

Outcome Measure Data

Analysis Population Description

ITT (efficacy cohort)

Arm/Group Title	Group 4 - Aml 10 mg + Olm 40 mg
Arm/Group Description
Measure Participants	133
Mean (Standard Error) [mm Hg]	-24.6 (1.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Overall Active Treatment Period
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No multiplicity adjustments
	Method	one-sample t-test
	Comments

Adverse Events

Time Frame	12 week treatment period plus 30 days after the last dose.
Adverse Event Reporting Description	Adverse events (AEs)were collected from the time of signing informed consent to the study and followup period (30 days). AEs were observed by the investigator (Inv) or reported by the participant. The nature of the event, time of onset, duration and intensity were documented together with the Inv assessment of the causal relationship to the drug.
Arm/Group Title	Amlodipine 5 mg		Amlodipine 5mg and Olmesartan 20 mg		Amlodipine 5mg and Olmesartan 40 mg		Amlodipine 10 mg and Olmesartan 40 mg
Arm/Group Description	All eligible participants began the active treatment period with amlodipine (Aml) 5 mg for Weeks 1-3. If blood pressure was greater than 120/80 at the end of 3 weeks, participants were titrated to the next regimen for weeks 4-6, and so on for weeks 7-9 and 10-12.		All eligible participants began the active treatment period with amlodipine (Aml) 5 mg for Weeks 1-3. If blood pressure was greater than 120/80 at the end of 3 weeks, participants were titrated to the next regimen for weeks 4-6, and so on for weeks 7-9 and 10-12.		All eligible participants began the active treatment period with amlodipine (Aml) 5 mg for Weeks 1-3. If blood pressure was greater than 120/80 at the end of 3 weeks, participants were titrated to the next regimen for weeks 4-6, and so on for weeks 7-9 and 10-12.		All eligible participants began the active treatment period with amlodipine (Aml) 5 mg for Weeks 1-3. If blood pressure was greater than 120/80 at the end of 3 weeks, participants were titrated to the next regimen for weeks 4-6, and so on for weeks 7-9 and 10-12.
All Cause Mortality
	Amlodipine 5 mg		Amlodipine 5mg and Olmesartan 20 mg		Amlodipine 5mg and Olmesartan 40 mg		Amlodipine 10 mg and Olmesartan 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Amlodipine 5 mg		Amlodipine 5mg and Olmesartan 20 mg		Amlodipine 5mg and Olmesartan 40 mg		Amlodipine 10 mg and Olmesartan 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/185 (0%)		0/180 (0%)		1/161 (0.6%)		1/134 (0.7%)
Injury, poisoning and procedural complications
Limb amputation	0/185 (0%)	0	0/180 (0%)	0	1/161 (0.6%)	0	0/134 (0%)	0
Vascular disorders
Transient ischemic attack	0/185 (0%)	0	0/180 (0%)	0	0/161 (0%)	0	1/134 (0.7%)	0
Other (Not Including Serious) Adverse Events
	Amlodipine 5 mg		Amlodipine 5mg and Olmesartan 20 mg		Amlodipine 5mg and Olmesartan 40 mg		Amlodipine 10 mg and Olmesartan 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/185 (4.3%)		23/180 (12.8%)		11/161 (6.8%)		12/134 (9%)
General disorders
Oedema Peripheral	3/185 (1.6%)		5/180 (2.8%)		2/161 (1.2%)		2/134 (1.5%)
Infections and infestations
Nasopharyngitis	1/185 (0.5%)		9/180 (5%)		2/161 (1.2%)		5/134 (3.7%)
Upper respiratory tract infection	1/185 (0.5%)		4/180 (2.2%)		3/161 (1.9%)		1/134 (0.7%)
Musculoskeletal and connective tissue disorders
Joint swelling	1/185 (0.5%)		2/180 (1.1%)		2/161 (1.2%)		3/134 (2.2%)
Nervous system disorders
Dizziness	2/185 (1.1%)		3/180 (1.7%)		2/161 (1.2%)		1/134 (0.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

"If identified by Daiichi Sankyo, Inc. (DSI), any of DSI's confidential information as defined herein shall be deleted…Nothing in this publication section shall be taken as giving DSI any right of editorial control over any publication prepared by Study Site."