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

This study has been completed.
Sponsor:
Information provided by:
Luitpold Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01363076
First received: May 27, 2011
Last updated: August 20, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Postoperative Pain
Drug: Ketorolac Tromethamine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of the Pharmacokinetics of Ketorolac Tromethamine Administered Intranasally (IN) for Postoperative Pain in Children Aged 12 Through 17 Years

Resource links provided by NLM:


Further study details as provided by Luitpold Pharmaceuticals:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 20
Study Start Date: June 2007
Study Completion Date: May 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketorolac Tromethamine (15 mg)
Ketorolac Tromethamine - single dose (15 mg) administered intranasally (IN) for subjects weighing <50 kg.
Drug: Ketorolac Tromethamine
Single IN dose of 15 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.
Drug: Ketorolac Tromethamine
Single IN dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01363076

Locations
United States, California
Stanford University Medical Center
Stanford, California, United States
Sponsors and Collaborators
Luitpold Pharmaceuticals
Investigators
Study Chair: Lincoln Bynum, MD ICON Developmental Solutions
  More Information

No publications provided

Responsible Party: David Bregman, M.D., Ph.D., Luitpold Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01363076     History of Changes
Other Study ID Numbers: ROX 2006-02
Study First Received: May 27, 2011
Results First Received: March 8, 2012
Last Updated: August 20, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Ketorolac Tromethamine
Ketorolac
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014