| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10015488 |
|
| 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 |
Main objective :
To identify the oral doses of PST2238 that are able to show a statistically significant difference on office sitting SBP in comparison to placebo. PST2238 will be administered at the oral doses of 0.05-0.15-0.5-1.5 and 5 mg to a target population of patients with mild hypertension |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives:
to compare the doses of PST2238 able to show a significant difference from placebo in the primary analysis, and to determine a responder profile, if any.
to identify the oral doses of PST2238 able to show a statistically significant difference on office sitting DBP versus placebo;
to identify, and eventually to compare, the oral doses of PST2238 which lead to statistically significant differences in overall 24-hour ambulatory SBP and/or DBP, day-time, night-time, awake and asleep, peak effect, trough effect, trough-to-peak ratio and time to peak effect, in comparison to placebo;
to verify if, at low doses, the BP lowering activity of PST2238 might be different according to the genetic variations in the enzyme precursors leading up to the Ouabain production and the level of Ouabain, whereas, at high doses, the activity of PST2238 might be different according to the adducin genotypes.
to determine the safety profile of a wide range of doses of PST2238.
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Run-in Period·
Age between 30 and 59 years.·
Patients with grade 1 or 2 of essential hypertension (according to the 2003 ESH/ESC Hypertension guidelines) with less than 3 of the following additional risk factors:
1)age > 55 years if male;
2)smoking;
3)dyslipidemia (total cholesterol ³250 mg/dl or LDL cholesterol ³155 mg/dl);
4)family history of cardiovascular disease occurring before 55 years in men or 65 years in women.·
Naive patients (never treated) or currently on antihypertensive monotherapy or on one combination tablet per day containing no more than two antihypertensive agents.·
Mean value of the last of 3 sitting systolic blood pressure (SBP) must range between 140 and 169 mmHg, when measured by OBP.·
Written informed consent.
Randomised Treatment Period·
Documented essential hypertension
At Visit 2 the mean of the last 3 consecutive readings must be SBP ³ 140, when measured by OBP.
At Visit 3, the mean of the last 3 consecutive readings must be SBP ³ 140 mmHg £ 169 mmHg, when measured by OBP. |
|
| E.4 | Principal exclusion criteria |
Run-in Period·
Secondary hypertension.·
Severe or malignant hypertension.·
Atrial Fibrillation·
Left and/or Right Ventricle Bundle Branch Block·
First degree AV-block exceeding 240 msec·
Electrocardiographic evidence of left ventricular hypertrophy, defined either as a Cornell voltage (6 mm adjustment in women) x QRS duration product exceeding 2440 mm x ms or as a Sokolow-Lyon voltage index of more than 38 mm (for technical details, see Circulation 1987; 75: 565-72 & JACC 1995; 26: 1022-29).
Cardiac disease requiring prohibited pharmacological treatment (for details see section 6.5) or history of myocardial infarction within the last 6 months.·
History of renal artery disease.·
Pregnant or nursing women or women of childbearing potential not taking anti-contraceptive medication.·
Surgery or disease of the gastrointestinal tract, which might influence absorption or elimination of the drug.·
Any concomitant condition that may, in the judgement of the investigator, jeopardise participant adherence to the protocol or ability to complete the trial (e.g., alcohol or drug abuse, disabling or terminal illness, personality or mental disorders, etc.).·
Concomitant therapy with medications that may affect blood pressure (for details see section 6.5).·
Treatment with any investigational drug in the previous 6 months.·
Predictable lack of cooperation. ·
Significant renal (serum Creatinine ³ 1.3 mg/dl or microalbuminuria in excess of 2.5 mg/mmol of creatinine in men or 3.5 mg/mmol of creatinine in women) or hepatic disease (SGOT and/or SGPT greater than 2 times the upper limit of the normal range) according to laboratory tests performed at screening visit if a previous evaluation in the 6 months preceding the screening visit is not available.·
Obesity > 30 kg/m2.·
Overt medically treated Diabetes mellitus.
Randomised Treatment Period·
Secondary hypertension.·
Severe or malignant hypertension.·
Atrial Fibrillation·
Left and/or Right Ventricle Bundle Branch Block·
First degree AV-block exceeding 240 msec·
Electrocardiographic evidence of left ventricular hypertrophy, defined either as a Cornell voltage (6 mm adjustment in women) x QRS duration product exceeding 2440 mm x ms or as a Sokolow-Lyon voltage index of more than 38 mm (for technical details, see Circulation 1987; 75: 565-72 & JACC 1995; 26: 1022-29). ·
Cardiac disease requiring prohibited pharmacological treatment (for technical details section 6.5) or history of myocardial infarction within the last 6 months.·
History of renal artery disease.·
Pregnant or nursing women or women of childbearing potential not taking anti-contraceptive medication.·
Surgery or disease of the gastrointestinal tract, which might influence absorption or elimination of the drug.·
Any concomitant condition that may, in the judgement of the investigator, jeopardise participant adherence to the protocol or ability to complete the trial (e.g., alcohol or drug abuse, disabling or terminal illness, personality or mental disorders, etc.).·
Concomitant therapy with medications that may affect blood pressure (for details see section 6.5).·
Prior or current autoimmune disease (leucopenia < 3500 / mm3 and/or neutropenia < 1000 / mm3·
Significant renal (serum Creatinine ³ 1.3 mg/dl or microalbuminuria in excess of 2.5 mg/mmol of creatinine in men or 3.5 mg/mmol of creatinine in women) or hepatic disease (SGOT and/or SGPT greater than 2 times the upper limit of the normal range) according to laboratory tests performed at screening visit if a previous evaluation in the 6 months preceding the screening visit is not available.·
Elevated values of sodium in urine (Na > 200 mmol/24 hours).·
Obesity > 30 kg/m2.·
Overt Medically Treated Diabetes mellitus.·
Predictable lack of cooperation. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The office sitting SBP will be the primary efficacy endpoint. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Information not present in EudraCT |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| 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 | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| The same medicinal product at different strengths |
|
| 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 | |
| E.8.9.1 | In the Member State concerned months | 18 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 18 |
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