Study to Determine the Pharmacokinetics and Pharmacodynamic Effects of Phenylephrine on BP Via IV

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the dose effect of Phenylephrine Hydrochloride Injection on the treatment of clinically relevant decreased blood pressure in the pediatric population, ≥12 to 16 year old patients undergoing general and neuraxial anesthesia. The secondary objectives are to describe changes in blood pressure and heart rate, time to onset and to maximal response, and the duration of response; to assess the safety of the product in this population; and to characterize the pharmacokinetics of phenylephrine hydrochloride.

Detailed Description
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This is a Phase 4 multi-center, randomized open-label study in 100 subjects aged ≥12 to 16 years who experience a decrease in blood pressure during a procedure requiring general or neuraxial anesthesia. At least 300 subjects will be enrolled in this study. It is anticipated that up to 33% of enrolled subjects will actually experience a decrease in blood pressure that requires treatment and so will receive Phenylephrine Hydrochloride Injection (PHI). There are 12 possible randomization assignments: one of six initial treatments PHI will be initially administered to approximately 50 subjects as an intravenous bolus (IV-B) at Low (1 μg/kg), Med (3 μg/kg), or High (5 μg/kg) level; PHI will be initially administered to approximately 50 subjects as a continuous intravenous infusion (IV-I) at Low (0.25 μg/kg/min), Med (0.75 μg/kg/min), or High (1.25 μg/kg/min) level]; each initial treatment group will have two pharmacokinetics (PK) sampling schedules.

Official Title
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Phase 4 Open Label Study to Determine Pharmacokinetics of Phenylephrine and Pharmacodynamic Effects on BP Via IV Admin of Phenylephrine Hydrochloride Inj in Ped Subjects (≥12 to 16 Years of Age) Undergoing Gen and Neuraxial Anesthesia

Conditions
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Hypotension

Intervention / Treatment
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* Drug: Phenylephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's age is between ≥12 and 16 years, inclusive Subject is scheduled for a procedure that requires general or neuraxial anesthesia Subjects must have normal or clinically acceptable physical exam Subjects with controlled diabetes prior to entry must have a mean systolic/diastolic office blood pressure ≤128/78 mmHg (sitting, after 5 minutes of rest) Females must have a urine or serum pregnancy test (Human Chorionic Gonadotropin) that is negative at Screening and Day 1 Subject's parent or legal guardian gives informed consent and subject gives assent. Exclusion Criteria: Subject has a contraindication to vasoconstrictor therapy for control of blood pressure Subject has participated in other clinical trials for investigational drugs and/or devices within 30 days prior to enrollment Subject has any serious medical condition which, in the opinion of the investigator, is likely to interfere with study procedures Subjects who have a history of any clinically significant local or systemic infectious disease within four weeks prior to initial treatment administration Subjects who are positive for hepatitis B surface antigen or hepatitis C antibody Subjects taking antihypertensive medication Subject is moribund (death is likely to occur in less than 48 hours) Females who are pregnant, nursing or unwilling to use/practice adequate contraception.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phenylephrine<br>Phenylephrine Hydrochloride Injection, USP (United States Pharmacopeia) 10 mg/mL label claim | Drug: Phenylephrine<br>* one of six initial treatments Phenylephrine Hydrochloride Injection (PHI) will be initially administered to approximately 50 subjects as an intravenous bolus (IV-B) at Low (1 μg/kg), Med (3 μg/kg), or High (5 μg/kg) level; PHI will be initially administered to approximately 50 subjects as a continuous intravenous infusion (IV-I) at Low (0.25 μg/kg/min), Med (0.75 μg/kg/min), or High (1.25 μg/kg/min) level]; each initial treatment group will have two PK sampling schedules.<br>* Other names: Phenylephrine Hydrochloride Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Phenylephrine (PE) concentrations will be measured using a validated liquid chromatography/mass spectrometry (LCMS/MS) assay. |  | Screening up to Day 3 |