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

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ClinicalTrials.gov Identifier: NCT00527514
Recruitment Status : Completed
First Posted : September 11, 2007
Results First Posted : September 23, 2009
Last Update Posted : November 11, 2009
Sponsor:
Information provided by:
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hypertension
Interventions Drug: Amlodipine
Drug: Olmesartan medoxomil plus amlodipine
Enrollment 185
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 Details 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
Hide 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 [1]
Not Completed 1
Reason Not Completed
Adverse Event             1
[1]
1 participant dropped out. 2 participants were subsequently mis-titrated to the third regimen.
Period Title: Weeks 4-6: Aml 5mg+Olmesartan 20 mg
Started 180 [1]
Completed 178
Not Completed 2
Reason Not Completed
Withdrawal by Subject             2
[1]
184 -2 who were mis-titrated -2 who met blood pressure goal = 180
Period Title: Weeks 7-9: Aml 5 mg + Olmesartan 40 mg
Started 161 [1]
Completed 158
Not Completed 3
Reason Not Completed
Adverse Event             1
Lost to Follow-up             1
Withdrawal by Subject             1
[1]
178 -19 who met blood pressure goal + 2 who were mis-titrated = 161
Period Title: Weeks 10-12:Aml 10 mg +Olmesartan 40 mg
Started 134 [1]
Completed 132
Not Completed 2
Reason Not Completed
Adverse Event             1
Withdrawal by Subject             1
[1]
158 -24 who met blood pressure goal = 134
Arm/Group Title Amlodipine and Olmesartan, if Necessary
Hide 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 Number of Baseline Participants 185
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 185 participants
56.8  (9.28)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 185 participants
Female
80
  43.2%
Male
105
  56.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 185 participants
Asian 14
Black or African American 26
White 144
American Indian or Alaska Native 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 185 participants
185
Stage of Hypertension   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 185 participants
Stage 1 82
Stage 2 103
[1]
Measure Description: Stage I hypertension is defined as systolic blood pressure (SBP) of 140 – 159 mmHg and diastolic blood pressure (DBP) of 90 – 99 mmHg; Stage II is defined as SBP ≥ 160 mmHg or DBP ≥ 100 mm Hg.
24-Hour Ambulatory Diastolic Blood Pressure  
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 185 participants
85.8  (7.91)
24-hour Ambulatory Systolic Blood Pressure  
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 185 participants
144.6  (10.88)
Heart Rate  
Mean (Standard Deviation)
Unit of measure:  Beats/minute
Number Analyzed 185 participants
75.1  (10.82)
Systolic Blood Pressure   [1] 
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 185 participants
158.2  (12.63)
[1]
Measure Description: Seated cuff measurement as opposed to ambulatory measurement.
1.Primary Outcome
Title Change From Baseline in Mean 24-hour Systolic Blood Pressure Measured by Ambulatory Monitoring
Hide Description [Not Specified]
Time Frame Baseline to 12 Weeks
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 172
Mean (Standard Deviation)
Unit of Measure: mm Hg
-21.4  (0.80)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No multiplicity adjustments
Method one-sample t-test
Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Daytime and Nighttime Ambulatory Systolic Blood Pressure
Hide Description [Not Specified]
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 172
Mean (Standard Deviation)
Unit of Measure: mm Hg
Daytime -23.1  (0.92)
Nighttime -18.5  (0.91)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No multiplicity adjustments
Method One-sample t-test
Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg Group.
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT (efficacy cohort)
Arm/Group Title Group 1 Amlodipine 5 mg
Hide Arm/Group Description:
All participants started the Active Treatment period with 5 mg of amlodipine for 3 weeks.
Overall Number of Participants Analyzed 185
Mean (Standard Deviation)
Unit of Measure: mm Hg
-10.1  (0.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1 Amlodipine 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No multiplicity adjustments
Method One-sample t-test
Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg + Olmesartan 20 mg Group.
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT (efficacy cohort)
Arm/Group Title Group 2 - Aml 5 mg + Olmesartan 20 mg
Hide 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.
Overall Number of Participants Analyzed 179
Mean (Standard Error)
Unit of Measure: mm Hg
-18.0  (0.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 2 - Aml 5 mg + Olmesartan 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No multiplicity adjustments
Method one-sample t-test
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg + Olmesartan 40 mg Group
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT (efficacy cohort)
Arm/Group Title Group 3 - Aml 5 mg + Olm 40 mg
Hide 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.
Overall Number of Participants Analyzed 160
Mean (Standard Error)
Unit of Measure: mm Hg
-20.5  (1.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 3 - Aml 5 mg + Olm 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No multiplicity adjustments
Method One-sample t-test
Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 10 mg + Olmesartan 40 mg Group
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT (efficacy cohort)
Arm/Group Title Group 4 - Aml 10 mg + Olm 40 mg
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 133
Mean (Standard Error)
Unit of Measure: mm Hg
-24.6  (1.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 4 - Aml 10 mg + Olm 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No multiplicity adjustments
Method one-sample t-test
Comments [Not Specified]
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide 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 (0.00%)      0/180 (0.00%)      1/161 (0.62%)      1/134 (0.75%)    
Injury, poisoning and procedural complications         
Limb amputation  1  0/185 (0.00%)  0 0/180 (0.00%)  0 1/161 (0.62%)  0/134 (0.00%)  0
Vascular disorders         
Transient ischemic attack  1  0/185 (0.00%)  0 0/180 (0.00%)  0 0/161 (0.00%)  0 1/134 (0.75%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
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 (4.32%)      23/180 (12.78%)      11/161 (6.83%)      12/134 (8.96%)    
General disorders         
Oedema Peripheral  1  3/185 (1.62%)  5/180 (2.78%)  2/161 (1.24%)  2/134 (1.49%) 
Infections and infestations         
Nasopharyngitis  1  1/185 (0.54%)  9/180 (5.00%)  2/161 (1.24%)  5/134 (3.73%) 
Upper respiratory tract infection  1  1/185 (0.54%)  4/180 (2.22%)  3/161 (1.86%)  1/134 (0.75%) 
Musculoskeletal and connective tissue disorders         
Joint swelling  1  1/185 (0.54%)  2/180 (1.11%)  2/161 (1.24%)  3/134 (2.24%) 
Nervous system disorders         
Dizziness  1  2/185 (1.08%)  3/180 (1.67%)  2/161 (1.24%)  1/134 (0.75%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
“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.”
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: John Raia
Organization: Daiichi Sankyo
Phone: (973) 630-2683
EMail: jraia@dsus.com
Layout table for additonal information
Responsible Party: William Waverczak, Daiichi Sankyo
ClinicalTrials.gov Identifier: NCT00527514     History of Changes
Other Study ID Numbers: 8663-402
First Submitted: September 10, 2007
First Posted: September 11, 2007
Results First Submitted: May 5, 2009
Results First Posted: September 23, 2009
Last Update Posted: November 11, 2009