E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020772 |
E.1.2 | Term | Hypertension |
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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 |
Primary objective: To evaluate a dose dependent reduction in MSSBP when comparing three doses of valsartan (0.25 mg,/kg, 1 mg/kg and 4 mg/kg ) over a 6 week period in children 1-5 years old with hypertension ( >= 95th percentile for age, gender, and height). |
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E.2.2 | Secondary objectives of the trial |
Secondary objective(s): To evaluate the overall safety and tolerability of valsartan in 1 to 5 year old hypertensive children when treated for up to 6 weeks. To evaluate blood pressure change at the end of Period 2 from end of Period 1, when comparing pooled valsartan patients versus pooled placebo patients |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
The investigator must ensure that all patients who meet all the inclusion criteria and none of the exclusion criteria are offered enrollment in the study. No additional exclusions can be applied by the investigator, in order that the study population will be representative of all eligible patients. 1. Patients who are eligible and able to participate in the study and whose parent(s)/guardian(s) consent in writing (written informed consent) to their doing so after the purpose and nature of the investigation has been clearly explained. 2. Male or female between the ages of 1 to 5 years, at visit 1 with a documented history of hypertension. 3. Must be able to swallow the liquid formulation of the study medication 4. Must be >=8 kg or <= 40 kg 5. Patients, either naïve or treated, must have a documented history of a mean seated systolic blood pressure (mean of three measurements), equal to or greater than 95th percentile for age, gender and height (Appendix 3). 6. Patients with uncontrolled blood pressure, receiving background antihypertensive therapy, may continue on this therapy provided there is no change in dosing regimen. 7. Patient that has had a previous solid organ transplantation more than 1 year ago. Patient must be on stable doses of immunosuppressive therapy and deemed clinically stable by the clinician. Stable doses of immunosuppressive therapy are defined as no change in frequency or total daily doses of immunosuppressive therapy for at least 3 months prior to screening. Doses of immunosuppressive therapy must be maintained throughout Periods 1 and 2 of the study. 8. Parent(s)/guardian(s) are able to follow verbal and/or written instructions in the local language |
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E.4 | Principal exclusion criteria |
Patients whose mean seated systolic blood pressure (mean of three measurements), at the baseline visit (Visit # 2) is >= 25% higher than the 95th percentile for age, gender and height see Appendix 3. 2. Physical examination of patient demonstrates abnormalities that would make this study medically hazardous to the patient. 3. Patients with background ARB therapy. 4. Patients that demonstrate any clinically significant abnormalities or clinically noteworthy abnormal laboratory values (other than those relating to renal function), including but not limited to the following: a. AST/SGOT or ALT/SGPT > 3 times the upper limit of the reference range b. Total bilirubin > 2 times the upper limit of the reference range c. Creatinine clearance < 30 mL/min/1.73m² (calculated using Modified Schwartz formula to estimate glomerular filtration rate [GFR], see section 7.5.5 for formula, based on the serum creatinine concentration obtained at Visit 1 (Screening). d. WBC count < 3000/mm³ e. Platelet count < 100,000/mm³ f. Serum potassium > upper limit of the reference range 5. Patients that demonstrate clinically significant ECG abnormalities other than those associated with left ventricular hypertrophy and AV block controlled with a pacemaker. Examples of clinically significant ECG abnormalities considered exclusionary are as follows: a. Heart Rate out of Range i. Rate < 60 BPM ii. Rate > 165 BPM b. Arrhythmia c. Supraventricular Tachycardia d. Ventricular Tachycardia e. Atrial Tachycardia (Fibrillation, Flutter, etc.) f. Conduction Abnormality g. Complete Atrioventricular Block (without Pacemaker) h. Second Degree AV Block, Type II (without Pacemaker) i. Sinus Node Dysfunction (Pause > 3 seconds or Bradycardia <45BPM) j. Sick Sinus Syndrome k. Repolarization Abnormality l. Prolonged rate-corrected QT (QTc) interval > 460 ms m. Acute Ischemia or Infarction 6. Patients that have coarctation of the aorta with a gradient of >= 30 mm Hg, or renal artery stenosis 7. Patient that has any clinically significant unstable medical condition or chronic disease that would put the patient at risk of experiencing an adverse event associated with the expected pharmacodynamic effects of the study medication. 8. Patient that has experienced a significant clinical illness within 10 days prior to baseline visit. 9. Patient that is known to have tested positive for the hepatitis B surface antigen or hepatitis C antibody. 10. Patient that is known to have tested seropositive for the human immunodeficiency virus (HIV) or patient is concomitantly receiving anti-retroviral therapy. 11. Patient that has a clinically significant abnormality of the hepatic system, or a history of malabsorption or previous gastrointestinal surgery that could affect drug absorption or metabolism. 12. Patient that has a known sensitivity to valsartan or other angiotensin II receptor blockers (ARB). 13. Patient receiving any of the prohibited medications listed in protocol section 6.6.5 unless these medications may be withdrawn ethically, prior to visit 1. 14. Patient has taken an investigational drug within 30 days prior to study drug administration |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is: - Change from baseline in MSSBP (mean sitting systolic blood pressure) The primary analysis is for change from baseline at the Period I endpoint in a dose dependent manner. Baseline is defined as the Week 0 value. The Period I endpoint is defined as the Week 6 value or the last post-baseline observation during Period I carried forward (LOCF). |
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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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |