The Pharmacokinetics of Ketorolac Tromethamine Administered Intranasally (IN) for Postoperative Pain in Children Aged 12 Through 17 Years

February 7, 2017 updated by: Egalet Ltd

A Study of the Pharmacokinetics of Ketorolac Tromethamine Administered Intranasally (IN) for Postoperative Pain in Children Aged 12 Through 17 Years

This was an open-label PK study in pediatric subjects who had undergone general surgery. Each subject's study participation consisted of a screening visit, a single-dose treatment with intranasal ketorolac (IN) tromethamine, and a follow-up visit.

Following surgery, subjects received IN ketorolac 15 mg (weight < 50 kg) or 30 mg (weight > or = 50 kg) when pain relief was indicated. For pain not relieved by the study drug, the subjects had access to an opioid analgesic administered by patient-controlled analgesia (PCA). Blood samples for pharmacokinetic analysis were obtained at specified time points following the dose of ketorolac.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Stanford, California, United States, 94305
        • Stanford University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 17 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Children aged 12 through 17 years
  • Body weight > or = 30 kg and < or = 100 kg
  • Female subjects of childbearing potential must have a negative serum or urine pregnancy test result prior to entry into the study
  • A legal representative able to provide written informed consent
  • Willing and able to comply with all testing and requirements defined in the protocol
  • Willing and able to complete the posttreatment visit

Exclusion Criteria:

  • Allergy or sensitivity to ketorolac or ethylene diamine tetraacetic acid (EDTA)
  • Allergic reaction to aspirin or other NSAIDs
  • Had an upper respiratory tract infection or other respiratory tract condition (eg, active allergic rhinitis) that could interfere with the absorption of the nasal spray or with the assessment of AEs
  • Use of any IN product within 24 hours prior to study entry
  • Clinically significant abnormality on screening laboratory tests
  • History of cocaine use resulting in nasal mucosal damage
  • History of peptic ulcer disease or gastrointestinal bleeding
  • Had advanced renal impairment or a risk for renal failure due to volume depletion
  • A history of any other clinically significant medical problem, which in the opinion of the investigator would interfere with study participation
  • Participation within 30 days of study entry or within 5 times the half-life, whichever is longer, in another investigational drug study
  • Allergy or significant reaction to opioids
  • Was pregnant or breastfeeding
  • Previously participated in this study
  • The surgical procedure involved head, neck, oral, or nasal surgery

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Ketorolac Tromethamine (15 mg)
Ketorolac Tromethamine - single dose (15 mg) administered intranasally (IN) for subjects weighing <50 kg.
Single IN dose of 15 mg ketorolac tromethamine for subjects weighing <50 kg.
Single IN dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.
EXPERIMENTAL: Ketorolac Tromethamine (30 mg)
Ketorolac Tromethamine - single dose (30 mg) administered intranasally (IN) for subjects weighing ≥50 kg.
Single IN dose of 15 mg ketorolac tromethamine for subjects weighing <50 kg.
Single IN dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cmax (the Maximum Observed Plasma Concentration)
Time Frame: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
Tmax (The Time to Maximum Observed Plasma Concentration; ie. The Time at Which Cmax Occured)
Time Frame: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Pro. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac. Individual plasma ketorolac concentrations were summarized by dose level for the PK population at each sampling time using n, arithmetic mean, SD, CV(%), geometric mean, 95% confidence intervals (CI) for the arithmetic mean, median, minimum, and maximum.
All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
AUClast (the Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Quantifiable Timepoint Post-dose)
Time Frame: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
AUCinf (the AUC Time From Zero to Infinity, Where Possible)
Time Frame: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Pro. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac. AUCinf calculated as: AUCinf = AUC(0-24) + (concentration at 24 hr/elimination constant).
All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
AUC 0-24 (the AUC From Time Zero to 24 Hours Post-dose
Time Frame: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
t1/2 (the Terminal Half-life, Where Possible)
Time Frame: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
MRT (Mean Residence Time)
Time Frame: All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose
Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Chair: Lincoln Bynum, MD, ICON Developmental Solutions

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2007

Primary Completion (ACTUAL)

January 1, 2008

Study Completion (ACTUAL)

May 1, 2008

Study Registration Dates

First Submitted

May 27, 2011

First Submitted That Met QC Criteria

May 27, 2011

First Posted (ESTIMATE)

June 1, 2011

Study Record Updates

Last Update Posted (ACTUAL)

March 16, 2017

Last Update Submitted That Met QC Criteria

February 7, 2017

Last Verified

February 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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