| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective is to compare the change from baseline in insulin resistance (IR, as measured by the Matsuda Index) in patients with hypertension and metabolic syndrome after 16 Weeks of monotherapy treatment with irbesartan relative to HCTZ. |
|
| E.2.2 | Secondary objectives of the trial |
1) To compare the change from baseline in insulin resistance (IR, as measured by the
Quicki Index) after 16 Weeks of monotherapy treatment with irbesartan relative to
HCTZ.
2) To compare the change from baseline in triglycerides, in BP, in hs-CRP after 16 Weeks of monotherapy treatment with irbesartan relative to HCTZ.
3) To compare the change from baseline in albumin/creatinine ratio after 16 Weeks of
monotherapy treatment with irbesartan relative to HCTZ.
4) To describe the changes from baseline in Matsuda Index, Quicki index, BP,
triglycerides, hs-CRP, and albumin/creatinine ratio after 28 Weeks of treatment with
a regimen of irbesartan + HCTZ.
5) To describe the changes from Week 16 to Week 28 in Matsuda Index, Quicki index,
BP, and triglycerides in the two randomized treatment groups.
6) To assess the safety and tolerability of irbesartan and HCTZ alone and in
combination.
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1) Subjects must be willing and able to provide written informed consent.
2) Uncontrolled hypertension defined as an averaged SeSBP ≥140 mmHg and/or an
averaged SeDBP ≥90 mmHg. Applies to both drug naive, and subjects receiving antihypertensive monotherapy.
3) Presenting at least 2 characteristics of metabolic syndrome other than BP, defined
according to the modified ATPIII* criteria and confirmed prior to randomization.
• Obesity confirmed by Waist circumference:
Men >94 cm (>37 in)
Women >80 cm (>32 in)
• Triglycerides >150 mg/dL
• HDL cholesterol
Men <40 mg/dL
Women <50 mg/dL
• Fasting plasma glucose ≥100 mg/dL (5.6 mmol/L) additionally, <126 mg/dL (7.0 mmol/L)
4) Men and women, ages ≥18 years
Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and up to four Weeks after the study in such a manner that the risk of pregnancy is minimized. |
|
| E.4 | Principal exclusion criteria |
1) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 4 Weeks after the study or Women who are pregnant or breastfeeding.
2) Subjects treated with any antidiabetic/antihyperglycemic medication, or with a fasting blood glucose ≥126 mg/dL.
3) SeSBP ≥180 mmHg and/or SeDBP ≥110 mmHg and/or evidence of malignant or
accelerated hypertension or clinical evidence that the subject requires immediate
lowering of their blood pressure within hours.
4) Known or suspected secondary hypertension.
5) Previous treatment with an ARB or ACE inhibitors within 4 months prior to
enrollment.
6) Hypertensive encephalopathy, stroke, or transient ischemic attack within the past
12 months.
7) Myocardial infarction, percutaneous transluminal coronary revascularization,
coronary artery bypass graft, or unstable angina pectoris within the past six months.
8) New York Heart Association (NYHA) functional class III-IV congestive heart failure,
or LV dysfunction requiring an ACE inhibitor or ARB.
9) Hemodynamically significant cardiac valvular disease
10) Heart block greater than first degree atrioventricular block, or preexcitation
syndrome, sick sinus syndrome, chronic atrial fibrillation, or chronic atrial flutter, or
other significant arrhythmias that may interfere with the blood pressure
measurements.
11) Significant chronic renal impairment, or renovascular disease
12) Significant liver disease
13) Systemic lupus erythematosus or other chromic autoimmune disease (with exception of Graves-Basadov disease).
14) Gastrointestinal disease or surgery that may interfere with drug absorption
15) Malignancy during the past five years (with exception of localized squamous cell or basal cell carcinoma of the skin, and/or local papillomas requiring no systemic
treatment).
16) Drug or alcohol abuse within the last five years
17) Non-fasting serum glucose ≥200 mg/dL (11.1 mmol/L), fasting serum glucose ≥126 mg/dL (6.9 mmol/L) [Analysis may be repeated once, if initial result is out of
range.]
18) Serum potassium < 3.3 or > 5.5 mmol/L [Analysis may be repeated once, if initial
result is out of range.]
19) Positive appearance of blood in the urine
20) Known hypersensitivity to irbesartan (or any other ARB), or HCTZ.
21) Oral or intramuscular corticosteroids and anabolic steroids are prohibited. (Only
short-term use of topical steroids and inhaled corticosteroids are allowed. No chronic
use permitted)
22) Any open-label antihypertensive medications (registered for the treatment of HTN
regardless of actual current indication)
23) Nitrates, and other vasodilators
24) Phosphodiesterase inhibitors for the treatment of erectile dysfunction (sildenafil,
tadalafil, and vardenafil) should not be taken in the 24 hours prior to any study visits
25) Chronic sympathomimetic drugs including bronchodilators, nasal sprays and oral
decongestants
26) Other bronchodilators
27) Potassium supplements
28) Lithium
29) Psychotropic drug therapy, anticonvulsant and antidepressant drugs
30) Antibiotics other than short (≤ 2 Week) courses
31) Protease inhibitors and reverse transcriptase inhibitors
32) Chronic NSAIDs, including COX-2 inhibitors (chronic defined as for seven days or
more) with the exception of low-dose aspirin therapy and occasional aspirin or NSAID use in customary doses
33) The use of fibrates within 12 months prior to entry into the Lead-In Phase are
prohibited, as well as during the course of the study
34) Statins and any other hypolipidemic medications must be initiated at least 2 months prior to enrollment into the study, and no dose modifications are allowed.
35) Antacid ingestion within two hours of study treatment
36) Herbal medications, food supplements, vitamin or mineral supplements are permitted unless the specific preparation is reviewed by the Investigator and found to have ingredients which have the potential to effect blood pressure, electrolyte, or glucose levels.
37) Immunosuppressant medication
38) Prisoners or subjects who are compulsorily detained (involuntarily incarceration) for the treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy outcome measure is the change in insulin resistance (IR) from
baseline to Week 16. The change in insulin resistance from baseline will be evaluated
again at Week 28. Other efficacy measures will be to compare the change from baseline in other metabolic parameters, and seated systolic (SeSBP) and diastolic (SeDBP) blood pressures at Weeks 16 and 28 between treatment groups. Clinical adverse events and laboratory measurements will assess safety outcomes. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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