A Randomized, Double-blinded, Placebo-controlled, Dose-ranging Study of Cardene® I.V. in Pediatric Subjects With Hypertension

Study Overview
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Brief Summary
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To define the relationship between Cardene I.V. dose, serum concentrations, and blood pressure reduction in pediatric subjects with hypertension.

Detailed Description
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Children with acute hypertensive episodes are frequently treated with the same marketed drugs as adults. Few drugs are specifically indicated for use in children with severe hypertension. Cardene I.V. has been widely used in children with severe hypertension without specific dosing recommendations for children in the labeling. This study is designed to examine the pharmacokinetics, pharmacodynamics, safety, and efficacy of using Cardene I.V. to reduce blood pressure (BP) in children with hypertension and will provide important information to guide use in pediatric patients.

Official Title
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A Randomized, Double-blinded, Placebo-controlled, Dose-ranging Study of Cardene® I.V. in Pediatric Subjects With Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Cardene® I.V.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of Stage 1 or Stage 2 systolic hypertension at the time of screening. Male or female subjects, ages ≥2 to ≤16 years. Females who meet either of the following criteria: Non-childbearing potential , as documented by: a medical history of non-menstruation or surgical sterility from oophorectomy and/or hysterectomy. * A history of tubal ligation or evidence of a sterile sexual partner is insufficient evidence of non-childbearing potential. Childbearing potential: provide a negative urine pregnancy test within 24 hours of administration of study drug and agree to utilize effective contraception or remain abstinent during the entire treatment and follow-up periods of the study. Signed informed consent provided by an authorized subject representative and assent from subject, if feasible (based on local Institutional Review Board (IRB)/ethics panel requirements). Exclusion Criteria: Subjects with seizures, altered state of consciousness, chest pain, facial palsy or intracranial hemorrhage at the time of screening. Receiving antihypertensive medication within a duration specified prior to screening. Treatment with cimetidine within 10 hours prior to dosing with study drug. Any known or suspected allergy to nicardipine hydrochloride. A calculated Glomerular Filtration Rate (GFR) under 30 mL/min/ 1.73 m2 as calculated using the Schwartz formula and the associated K values. Known history of severe aortic stenosis. Known history of severe left ventricular dysfunction. Known history of severely impaired hepatic function with portal hypertension. Liver function test (AST or ALT) results greater than or equal to twice the upper limit of normal. Receiving maintenance hemodialysis at screening or anticipated to require hemodialysis within 12 hours following initiation of treatment with study drug. Receiving a blood transfusion at screening or anticipated to require blood transfusions within 12 hours following initiation of treatment with study drug. Lack of appropriate intravenous (I.V.) access. Inability to tolerate a large-volume I.V. infusion. Any other condition or prior therapy, which, in the opinion of the investigator, would make the subject unsuitable for this study. Participation in any phase of another clinical research study involving the evaluation of another investigational drug or device within 30 days before randomization.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: Cardene® I.V.<br>* 5 mcg/kg/min Cardene I.V. 2.5 mcg/kg/min Cardene I.V. 0.5 mcg/kg/min Cardene I.V.<br>|
| Experimental: 2<br>5 mcg | Drug: Cardene® I.V.<br>* 5 mcg/kg/min Cardene I.V. 2.5 mcg/kg/min Cardene I.V. 0.5 mcg/kg/min Cardene I.V.<br>|
| Experimental: 3<br>2.5 | Drug: Cardene® I.V.<br>* 5 mcg/kg/min Cardene I.V. 2.5 mcg/kg/min Cardene I.V. 0.5 mcg/kg/min Cardene I.V.<br>|
| Experimental: 4<br>0.5 | Drug: Cardene® I.V.<br>* 5 mcg/kg/min Cardene I.V. 2.5 mcg/kg/min Cardene I.V. 0.5 mcg/kg/min Cardene I.V.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean percent change in SBP (Systolic Blood Pressure) from baseline during the 30-minute Randomized, Placebo-controlled Infusion Phase for each dose level of Cardene I.V. compared to placebo. |  | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1) Mean percent change in SBP and DBP between various phases of dosing. 2) Proportion of subjects requiring additional antihypertensive medications during the treatment period. 3) Mean effective dose of Cardene I.V. |  | 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, High Blood Pressure, Pediatric Hypertension, High blood pressure in children