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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hypotension
• Intervention / Treatment: Drug: Phenylephrine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: J. Barton Kalis; Phone Number: 856-489-2247; Email: jkalis@hikma.com

Study Locations

• United States
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Withdrawn
      • Alfred I. DuPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Terminated
      • Children's National Medical Center
  • Florida
    • Miami, Florida, United States, 33136-1005
      • Recruiting
      • Jackson Memorial Hospital
      • Contact: J. Barton Kalis; Phone Number: 856-489-2247; Email: jkalis@hikma.com
  • Georgia
    • Atlanta, Georgia, United States, 30322-1062
      • Terminated
      • Children's Healthcare of Atlanta at Egleston
  • Mississippi
    • Jackson, Mississippi, United States, 39126
      • Terminated
      • University of Mississippi Medical Center
  • New York
    • Stony Brook, New York, United States, 11794
      • Terminated
      • Stony Brook Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: J. Barton Kalis; Phone Number: 856-489-2247; Email: jkalis@hikma.com
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • Children's Medical Center of Dallas
      • Contact: J.Barton Kalis; Phone Number: 856-489-2247; Email: jkalis@hikma.com
  • Washington
    • Seattle, Washington, United States, 98105
      • Withdrawn
      • Seattle Children's Hospital
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Terminated
      • Ruby Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 16 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Subject's age is between ≥12 and 16 years, inclusive
2. Subject is scheduled for a procedure that requires general or neuraxial anesthesia
3. Subjects must have normal or clinically acceptable physical exam
4. 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)
5. Females must have a urine or serum pregnancy test (Human Chorionic Gonadotropin) that is negative at Screening and Day 1
6. Subject's parent or legal guardian gives informed consent and subject gives assent.

Exclusion Criteria:

1. Subject has a contraindication to vasoconstrictor therapy for control of blood pressure
2. Subject has participated in other clinical trials for investigational drugs and/or devices within 30 days prior to enrollment
3. Subject has any serious medical condition which, in the opinion of the investigator, is likely to interfere with study procedures
4. Subjects who have a history of any clinically significant local or systemic infectious disease within four weeks prior to initial treatment administration
5. Subjects who are positive for hepatitis B surface antigen or hepatitis C antibody
6. Subjects taking antihypertensive medication
7. Subject is moribund (death is likely to occur in less than 48 hours)
8. Females who are pregnant, nursing or unwilling to use/practice adequate contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Phenylephrine; Phenylephrine Hydrochloride Injection, USP (United States Pharmacopeia) 10 mg/mL label claim

Drug: Phenylephrine; 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.; Other Names: Phenylephrine Hydrochloride Injection

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: West-Ward Pharmaceutical
• Investigators: Study Director: Cesar Ormeno, MD, PRA Health Sciences

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 17, 2014
• First Submitted That Met QC Criteria: December 22, 2014
• First Posted (Estimated): December 23, 2014

Study Record Updates

• Last Update Posted (Actual): July 23, 2024
• Last Update Submitted That Met QC Criteria: July 22, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: 1420RDP009