Clinical Trial Results:
Olmesartan + Amlodipine treatment in diabetic patients: evaluating blood pressure control after 48 hours from the last administration (missed dose).
Summary
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EudraCT number |
2010-018774-21 |
Trial protocol |
ES FR DE GR IT |
Global end of trial date |
15 May 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Feb 2016
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First version publication date |
06 Aug 2015
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MeIn/08/OLMAML-Hyp/001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Menarini International Operations Luxembourg S.A.
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Sponsor organisation address |
1, Avenue de la Gare, Luxembourg, Luxembourg, L-1611
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Public contact |
Medical Scientific Management, Menarini International Operations Luxembourg S.A., +352 264976,
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Scientific contact |
Menarini Corporate Medical Department, Menarini Industrie Farmaceutiche Riunite, +39 05556801,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 May 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
15 May 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine whether the Olmesartan (OLM) 20-40 mg + Amlodipine (AML) 5-10 mg combination was at least as effective as the Perindopril (PER) 4-8 mg + Amlodipine 5-10 mg combination in reducing office diastolic blood pressure after 24 weeks of treatment, at 48 hours from last administration (missed dose).
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice (GCP) guidelines and local law requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Dec 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 14
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Country: Number of subjects enrolled |
Greece: 25
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Country: Number of subjects enrolled |
Spain: 34
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Country: Number of subjects enrolled |
Italy: 187
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Worldwide total number of subjects |
260
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EEA total number of subjects |
260
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
187
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From 65 to 84 years |
73
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85 years and over |
0
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Recruitment
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Recruitment details |
Total recruitment period (first patient in to last patient in): about 152 weeks (03/12/2010-31/10/2013). | ||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
The pre-assignment period was a run-in period, open-label, during which the eligible patients took one Amlodipine 5 mg tablet every day for 7 or 14 days (for 1 or 2 weeks), depending on previous subject’s treatment(s). | ||||||||||||||||||||||||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
335 [1] | ||||||||||||||||||||||||||||||||||||
Number of subjects completed |
260 | ||||||||||||||||||||||||||||||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Inclusion or exclusion criteria not met: 62 | ||||||||||||||||||||||||||||||||||||
Reason: Number of subjects |
Adverse event, non-fatal: 4 | ||||||||||||||||||||||||||||||||||||
Reason: Number of subjects |
Consent withdrawn by subject: 8 | ||||||||||||||||||||||||||||||||||||
Reason: Number of subjects |
missing reason: 1 | ||||||||||||||||||||||||||||||||||||
Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: All the 335 patients screened for the study entered a pre-randomization run-in period of 7-14 days with Amlodipine 5 mg once a day (pre-assignment period). Out of these 335 subjects, 260 were randomized to one of the two study treatments, hence entering in baseline period (=period 1) population. |
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||||||||||||||||||||
Blinding implementation details |
The “double-dummy” technique with matching placebo guaranteed the maintenance of the clinical study double-blind conditions.
No blinding was used during the run-in period, when all patients received amlodipine 5mg tablet once-a-day.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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OLM/AML | ||||||||||||||||||||||||||||||||||||
Arm description |
Olmesartan 20 mg + Amlodipine 5 mg FDC coated tablets, once a day, by oral route Olmesartan 40 mg + Amlodipine 5 mg FDC coated tablets, once a day, by oral route Olmesartan 40 mg + Amlodipine 10 mg FDC coated tablets, once a day, by oral route For the first 12 weeks of randomised double-blind treatment, patients randomized to OLM/AML received a combination of Olmesartan 20 mg + Amlodipine 5 mg once-daily. In patients not normalised by treatment after 12 weeks the dose of drug treatment was up-titrated to Olmesartan 40 mg + Amlodipine 5 mg once-daily. In patients not yet normalised after additional 6 weeks of treatment (week 18) the dose of drug treatment was further up-titrated to Olmesartan 40 mg + Amlodipine 10 mg once-daily. At visit 6a patients received placebo treatment (one capsule and one tablet) in a single blind for 1 day. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Olmesartan + amlodipine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
For the first 12 weeks of randomised double-blind treatment, patients randomized to OLM/AML received a combination of Olmesartan 20 mg + Amlodipine 5 mg once-daily.
In patients not normalised by treatment after 12 weeks the dose of drug treatment was up-titrated to Olmesartan 40 mg + Amlodipine 5 mg once-daily.
In patients not yet normalised after additional 6 weeks of treatment (week 18) the dose of drug treatment was further up-titrated to Olmesartan 40 mg + Amlodipine 10 mg once-daily. At visit 6a patients received placebo treatment (one capsule and one tablet) in a single blind for 1 day.
All drugs were administered orally, in the morning, at breakfast time, with a glass of water.
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Arm title
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PER/AML | ||||||||||||||||||||||||||||||||||||
Arm description |
Perindopril /Amlodipine fixed dose capsule, once a day, by oral route Perindopril 4mg/Amlodipine 5 mg fixed dose capsule Perindopril 8mg/Amlodipine 5 mg fixed dose capsule Perindopril 8mg/Amlodipine 10 mg fixed dose capsule For the first 12 weeks of randomised double-blind treatment, patients randomized to PER/AML received Perindopril 4 mg + Amlodipine 5 mg once-daily. In patients not normalised by treatment after 12 weeks the dose of drug treatment was up-titrated to Perindopril 8 mg + Amlodipine 5 mg once-daily. In patients not yet normalised after additional 6 weeks of treatment (week 18) the dose of drug treatment was further up-titrated to Perindopril 8 mg + Amlodipine 10 mg once-daily. At visit 6a patients received placebo treatment (one placebo capsule and one placebo tablet) in a single blind for 1 day | ||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Perindopril and amlodipine fixed combination
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
For the first 12 weeks of randomised double-blind treatment, patients randomized to PER/AML received Perindopril 4 mg + Amlodipine 5 mg once-daily. In patients not normalised by treatment after 12 weeks the dose of drug treatment was be up-titrated to Perindopril 8 mg +
Amlodipine 5 mg once-daily. In patients not yet normalised after additional 6 weeks of treatment (week 18) the dose of drug treatment was further up-titrated to Perindopril 8 mg + Amlodipine 10 mg once-daily. At visit 6a patients received placebo treatment (one placebo
capsule and one placebo tablet) in a single blind for 1 day. All drugs were administered orally, in the morning, at breakfast time, with a glass of water.
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Baseline characteristics reporting groups
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Reporting group title |
OLM/AML
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Reporting group description |
Olmesartan 20 mg + Amlodipine 5 mg FDC coated tablets, once a day, by oral route Olmesartan 40 mg + Amlodipine 5 mg FDC coated tablets, once a day, by oral route Olmesartan 40 mg + Amlodipine 10 mg FDC coated tablets, once a day, by oral route For the first 12 weeks of randomised double-blind treatment, patients randomized to OLM/AML received a combination of Olmesartan 20 mg + Amlodipine 5 mg once-daily. In patients not normalised by treatment after 12 weeks the dose of drug treatment was up-titrated to Olmesartan 40 mg + Amlodipine 5 mg once-daily. In patients not yet normalised after additional 6 weeks of treatment (week 18) the dose of drug treatment was further up-titrated to Olmesartan 40 mg + Amlodipine 10 mg once-daily. At visit 6a patients received placebo treatment (one capsule and one tablet) in a single blind for 1 day. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PER/AML
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Reporting group description |
Perindopril /Amlodipine fixed dose capsule, once a day, by oral route Perindopril 4mg/Amlodipine 5 mg fixed dose capsule Perindopril 8mg/Amlodipine 5 mg fixed dose capsule Perindopril 8mg/Amlodipine 10 mg fixed dose capsule For the first 12 weeks of randomised double-blind treatment, patients randomized to PER/AML received Perindopril 4 mg + Amlodipine 5 mg once-daily. In patients not normalised by treatment after 12 weeks the dose of drug treatment was up-titrated to Perindopril 8 mg + Amlodipine 5 mg once-daily. In patients not yet normalised after additional 6 weeks of treatment (week 18) the dose of drug treatment was further up-titrated to Perindopril 8 mg + Amlodipine 10 mg once-daily. At visit 6a patients received placebo treatment (one placebo capsule and one placebo tablet) in a single blind for 1 day | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
OLM/AML - safety
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The safety population set included all randomised patients who had taken at least one dose of study medication.
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Subject analysis set title |
PER/AML - safety
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The safety population set included all randomised patients who had taken at least one dose of study medication.
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Subject analysis set title |
OLM/AML - FAS
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Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
“Full Analysis Set” (FAS): according to the “Intention-to-Treat” (ITT) principle, this set included all randomised patients who took at least one dose of the study medication and with a baseline and at least one post-baseline efficacy assessment of sitting ODBP.
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Subject analysis set title |
PER/AML - FAS
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Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
“Full Analysis Set” (FAS): according to the “Intention-to-Treat” (ITT) principle, this set included all randomised patients who took at least one dose of the study medication and with a baseline and at least one post-baseline efficacy assessment of sitting ODBP.
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End points reporting groups
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Reporting group title |
OLM/AML
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Reporting group description |
Olmesartan 20 mg + Amlodipine 5 mg FDC coated tablets, once a day, by oral route Olmesartan 40 mg + Amlodipine 5 mg FDC coated tablets, once a day, by oral route Olmesartan 40 mg + Amlodipine 10 mg FDC coated tablets, once a day, by oral route For the first 12 weeks of randomised double-blind treatment, patients randomized to OLM/AML received a combination of Olmesartan 20 mg + Amlodipine 5 mg once-daily. In patients not normalised by treatment after 12 weeks the dose of drug treatment was up-titrated to Olmesartan 40 mg + Amlodipine 5 mg once-daily. In patients not yet normalised after additional 6 weeks of treatment (week 18) the dose of drug treatment was further up-titrated to Olmesartan 40 mg + Amlodipine 10 mg once-daily. At visit 6a patients received placebo treatment (one capsule and one tablet) in a single blind for 1 day. | ||
Reporting group title |
PER/AML
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Reporting group description |
Perindopril /Amlodipine fixed dose capsule, once a day, by oral route Perindopril 4mg/Amlodipine 5 mg fixed dose capsule Perindopril 8mg/Amlodipine 5 mg fixed dose capsule Perindopril 8mg/Amlodipine 10 mg fixed dose capsule For the first 12 weeks of randomised double-blind treatment, patients randomized to PER/AML received Perindopril 4 mg + Amlodipine 5 mg once-daily. In patients not normalised by treatment after 12 weeks the dose of drug treatment was up-titrated to Perindopril 8 mg + Amlodipine 5 mg once-daily. In patients not yet normalised after additional 6 weeks of treatment (week 18) the dose of drug treatment was further up-titrated to Perindopril 8 mg + Amlodipine 10 mg once-daily. At visit 6a patients received placebo treatment (one placebo capsule and one placebo tablet) in a single blind for 1 day | ||
Subject analysis set title |
OLM/AML - safety
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety population set included all randomised patients who had taken at least one dose of study medication.
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Subject analysis set title |
PER/AML - safety
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety population set included all randomised patients who had taken at least one dose of study medication.
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Subject analysis set title |
OLM/AML - FAS
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
“Full Analysis Set” (FAS): according to the “Intention-to-Treat” (ITT) principle, this set included all randomised patients who took at least one dose of the study medication and with a baseline and at least one post-baseline efficacy assessment of sitting ODBP.
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Subject analysis set title |
PER/AML - FAS
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
“Full Analysis Set” (FAS): according to the “Intention-to-Treat” (ITT) principle, this set included all randomised patients who took at least one dose of the study medication and with a baseline and at least one post-baseline efficacy assessment of sitting ODBP.
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End point title |
Change from baseline in office brachial sitting DBP | ||||||||||||
End point description |
The office DBP measurement was done at the brachial artery level, after 24 weeks of active treatment, when patients were in sitting position, at 48h from the last administration (missed dose).
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End point type |
Primary
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End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
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Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
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Number of subjects included in analysis |
256
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||
P-value |
= 0.058 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.886
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.129 | ||||||||||||
upper limit |
2.902 | ||||||||||||
Notes [1] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
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End point title |
Change from baseline in sitting office SBP | ||||||||||||
End point description |
The office SBP measurement was done after 24 weeks of active treatment, when patients were in sitting position, at 48h from the last administration (missed dose).
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End point type |
Secondary
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End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
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Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
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Number of subjects included in analysis |
256
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [2] | ||||||||||||
P-value |
= 0.012 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
3.129
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.112 | ||||||||||||
upper limit |
6.369 | ||||||||||||
Notes [2] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
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End point title |
Change from baseline of sitting office SBP | ||||||||||||
End point description |
The office SBP measurement was done after 24 weeks of active treatment.
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End point type |
Secondary
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End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
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Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
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Number of subjects included in analysis |
256
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | ||||||||||||
P-value |
= 0.012 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
2.713
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.521 | ||||||||||||
upper limit |
5.947 | ||||||||||||
Notes [3] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
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End point title |
Change from baseline in sitting office DBP | ||||||||||||
End point description |
The office DBP measurement was done after 24 weeks of active treatment.
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End point type |
Secondary
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End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
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Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
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Number of subjects included in analysis |
256
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [4] | ||||||||||||
P-value |
= 0.058 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.695
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.316 | ||||||||||||
upper limit |
2.705 | ||||||||||||
Notes [4] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
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End point title |
Change from baseline in sitting office pulse pressure | ||||||||||||
End point description |
The pulse pressure measurement was done after 24 weeks of active treatment at 48h from the last administration (missed dose).
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End point type |
Secondary
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End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
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Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
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Number of subjects included in analysis |
256
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [5] | ||||||||||||
P-value |
= 0.099 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
2.194
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.341 | ||||||||||||
upper limit |
4.729 | ||||||||||||
Notes [5] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in sitting office pulse pressure | ||||||||||||
End point description |
The pulse pressure measurement was done after 24 weeks of active treatment at 48h from the last administration (missed dose).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
PER/AML - FAS v OLM/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
256
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [6] | ||||||||||||
P-value |
= 0.099 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
1.967
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.562 | ||||||||||||
upper limit |
4.496 | ||||||||||||
Notes [6] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Percentage of subjects with office sitting BP < 130/80 mmHg | ||||||||||||
End point description |
Rate of normalized subjects with Office sitting blood pressure <130/80 at V6a vs. baseline
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
247
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.5388 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||
Point estimate |
0.0377
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.0654 | ||||||||||||
upper limit |
0.1408 |
|
|||||||||||||
End point title |
Percentage of subjects with office sitting BP < 130/80 mmHg | ||||||||||||
End point description |
Rate of normalized subjects with Office sitting blood pressure <130/80 at V6b vs. baseline.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
PER/AML - FAS v OLM/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
245
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [7] | ||||||||||||
P-value |
= 0.5056 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||
Point estimate |
-0.029
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.1003 | ||||||||||||
upper limit |
0.0423 | ||||||||||||
Notes [7] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Percentage of subjects with a sitting office SBP reduction of at least 20 mmHg or a sitting office DBP reduction of at least 10 mmHg | ||||||||||||
End point description |
Rate of responders subjects at V6a vs. baseline
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
247
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [8] | ||||||||||||
P-value |
= 0.2351 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||
Point estimate |
0.0671
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.0388 | ||||||||||||
upper limit |
0.173 | ||||||||||||
Notes [8] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Percentage of subjects with a sitting office SBP reduction of at least 20 mmHg or a sitting office DBP reduction of at least 10 mmHg | ||||||||||||
End point description |
Rate of responders subjects at V6b vs. baseline.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
245
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [9] | ||||||||||||
P-value |
= 0.5134 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||
Point estimate |
0.0417
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.0797 | ||||||||||||
upper limit |
0.1631 | ||||||||||||
Notes [9] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in (aortic) central SBP | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
PER/AML - FAS v OLM/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
75
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [10] | ||||||||||||
P-value |
= 0.007 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
6.591
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.452 | ||||||||||||
upper limit |
12.73 | ||||||||||||
Notes [10] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in (aortic) central SBP | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
75
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [11] | ||||||||||||
P-value |
= 0.007 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
8.155
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.861 | ||||||||||||
upper limit |
14.45 | ||||||||||||
Notes [11] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in (aortic) central DBP | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
75
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [12] | ||||||||||||
P-value |
= 0.076 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
2.292
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.705 | ||||||||||||
upper limit |
6.288 | ||||||||||||
Notes [12] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in (aortic) central DBP | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
75
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [13] | ||||||||||||
P-value |
= 0.076 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
4.194
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.106 | ||||||||||||
upper limit |
8.282 | ||||||||||||
Notes [13] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in central pulse pressure | ||||||||||||
End point description |
Change in central pulse pressure after 24 weeks of treatment
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
69
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [14] | ||||||||||||
P-value |
= 0.051 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
4.242
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.353 | ||||||||||||
upper limit |
8.837 | ||||||||||||
Notes [14] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in central pulse pressure | ||||||||||||
End point description |
Change in central pulse pressure at 48 hours from last administration (missed dose)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
69
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [15] | ||||||||||||
P-value |
= 0.051 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
3.944
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.759 | ||||||||||||
upper limit |
8.646 | ||||||||||||
Notes [15] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in P1 height | ||||||||||||
End point description |
Change in P1 height (outgoing pressure wave) after 24 weeks of treatment
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
75
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [16] | ||||||||||||
P-value |
= 0.125 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
2.554
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.331 | ||||||||||||
upper limit |
5.438 | ||||||||||||
Notes [16] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in P1 height | ||||||||||||
End point description |
Change in P1 height (outgoing pressure wave) at 48 hours from last administration (missed dose)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
75
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [17] | ||||||||||||
P-value |
= 0.125 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
1.766
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.187 | ||||||||||||
upper limit |
4.719 | ||||||||||||
Notes [17] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in ΔP | ||||||||||||
End point description |
Change in ΔP (augmentation) after 24 weeks of treatment
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
69
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [18] | ||||||||||||
P-value |
= 0.016 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
2.197
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.252 | ||||||||||||
upper limit |
4.646 | ||||||||||||
Notes [18] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in ΔP | ||||||||||||
End point description |
Change in ΔP (augmentation) at 48 hours from last administration (missed dose)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
69
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [19] | ||||||||||||
P-value |
= 0.016 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
2.776
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.263 | ||||||||||||
upper limit |
5.289 | ||||||||||||
Notes [19] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in Augmentation Index | ||||||||||||
End point description |
Change in Augmentation Index after 24 weeks of treatment
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
75
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [20] | ||||||||||||
P-value |
= 0.012 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
2.407
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.074 | ||||||||||||
upper limit |
5.888 | ||||||||||||
Notes [20] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in Augmentation Index | ||||||||||||
End point description |
Change in Augmentation Index at 48 hours from last administration (missed dose)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
75
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [21] | ||||||||||||
P-value |
= 0.012 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
4.179
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.587 | ||||||||||||
upper limit |
7.772 | ||||||||||||
Notes [21] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in pulse pressure amplification | ||||||||||||
End point description |
Change in pulse pressure amplification after 24 weeks of treatment
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
75
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [22] | ||||||||||||
P-value |
= 0.024 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.02796
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.0792 | ||||||||||||
upper limit |
0.0232 | ||||||||||||
Notes [22] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in pulse pressure amplification | ||||||||||||
End point description |
Change in pulse pressure amplification at 48 hours from last administration (missed dose)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
75
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [23] | ||||||||||||
P-value |
= 0.024 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.05236
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.1052 | ||||||||||||
upper limit |
0.0005 | ||||||||||||
Notes [23] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in PWV | ||||||||||||
End point description |
Change in Pulse wave velocity after 24 weeks of treatment
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
56
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [24] | ||||||||||||
P-value |
= 0.0815 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.7849
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.058 | ||||||||||||
upper limit |
1.512 | ||||||||||||
Notes [24] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Change from baseline in PWV | ||||||||||||
End point description |
Change in Pulse wave velocity at 48 hours from last administration (missed dose)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
56
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [25] | ||||||||||||
P-value |
= 0.0815 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.9259
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.214 | ||||||||||||
upper limit |
1.638 | ||||||||||||
Notes [25] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Percentage of normalized subjects with office sitting blood pressure <140/85 mmHg | ||||||||||||
End point description |
Exploratory endpoint established before unblinding
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
At Visit 6a (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
247
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [26] | ||||||||||||
P-value |
= 0.3735 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||
Point estimate |
0.06
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.0643 | ||||||||||||
upper limit |
0.1843 | ||||||||||||
Notes [26] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||
End point title |
Percentage of normalized subjects with office sitting blood pressure <140/85 mmHg | ||||||||||||
End point description |
Exploratory endpoint established before unblinding
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
At Visit 6b (or alternatively at early withdrawal)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OLM/AML vs PER/AML | ||||||||||||
Comparison groups |
OLM/AML - FAS v PER/AML - FAS
|
||||||||||||
Number of subjects included in analysis |
245
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [27] | ||||||||||||
P-value |
= 0.5827 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||
Point estimate |
0.0373
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.0789 | ||||||||||||
upper limit |
0.1536 | ||||||||||||
Notes [27] - The statistical analyses were aimed to assess the non-inferiority and safety of combination Olmesartan + Amlodipine in comparison with Perindopril + Amlodipine. |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
Safety measurements are recorded at each visit from Visit 2 to Visit 6b.
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.4
|
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Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
OLM/AML - safety
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PER/AML - safety
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
24 Jan 2011 |
Amendment 1 was implemented in order to:
- clarify how to manage the inclusion of patients taking Beta-blockers;
- clarify how to perform PWV;
- modify the exclusion criterion based on creatinine values, adding correct values;
- correct definition of responder patients;
- notify the change of the responsible person for co-ordination of monitoring activities at CRO |
||
29 Jun 2011 |
Amendment 2 was implemented in order to:
- allow inclusion of patients already treated with a combination therapy;
- withdraw patients with SBP/DBP lower than 120/70;
- clarify that previous HbA1c assessment was not necessary and that it could be analysed at V1 to be available at V2 before randomization;
- correct typing errors. |
||
09 Jul 2012 |
Amendment 3 was implemented in order to:
- modify study phase from III to IV, Olmesartan + Amlodipine at all different dosages used in the study being available on Italian market;
- add 30 Italian sites in the study, after the closure of all other sites located in France, Germany, Greece, Switzerland and Spain, due to low recruitment rate;
- better describe Perindopril treatment and placebo;
- change formulation for Perindopril + Amlodipine and related placebo from encapsulated in DB capsules size AA for oral use to tablets;
- better describe study drugs packaging and labelling;
- remind placebo administration at V6a;
- turn CBP into optional assessment at V2, V4, V5, V6a and V6b or withdrawal, maintaining centralized reading;
- correct typing errors;
- notify the change of the responsible person for co-ordination of monitoring activities at CRO |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
No limitations or caveats are applicable to this summary. |