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

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

Study Overview

• Status: Withdrawn
• Conditions: Hypertension
• Intervention / Treatment: Drug: Cardene® I.V.

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
  • Florida
    • Miami, Florida, United States, 33145

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

    1. a medical history of non-menstruation or
    2. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1	Drug: Cardene® I.V.; 5 mcg/kg/min Cardene I.V.; 2.5 mcg/kg/min Cardene I.V.; 0.5 mcg/kg/min Cardene I.V.
Experimental: 2; 5 mcg	Drug: Cardene® I.V.; 5 mcg/kg/min Cardene I.V.; 2.5 mcg/kg/min Cardene I.V.; 0.5 mcg/kg/min Cardene I.V.
Experimental: 3; 2.5	Drug: Cardene® I.V.; 5 mcg/kg/min Cardene I.V.; 2.5 mcg/kg/min Cardene I.V.; 0.5 mcg/kg/min Cardene I.V.
Experimental: 4; 0.5	Drug: Cardene® I.V.; 5 mcg/kg/min Cardene I.V.; 2.5 mcg/kg/min Cardene I.V.; 0.5 mcg/kg/min Cardene I.V.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Facet Biotech

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: September 10, 2007
• First Submitted That Met QC Criteria: September 11, 2007
• First Posted (Estimate): September 12, 2007

Study Record Updates

• Last Update Posted (Estimate): March 16, 2012
• Last Update Submitted That Met QC Criteria: March 15, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Hypertension, High Blood Pressure, Pediatric Hypertension, High blood pressure in children
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Nicardipine
• Other Study ID Numbers: Cardene® I.V. 1406