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

NCT01363076 | Completed Phase 1 Results

• 1 other identifier: ROX 2006-02
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postoperative Pain

Outcome Measures

Primary Outcomes (7)

• Cmax (the Maximum Observed Plasma Concentration)

  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)

  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)

  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)

  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

  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)

  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)

  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

Study Arms (2)

Ketorolac Tromethamine (15 mg)

EXPERIMENTAL

Ketorolac Tromethamine - single dose (15 mg) administered intranasally (IN) for subjects weighing \<50 kg.

Drug: Ketorolac Tromethamine

Ketorolac Tromethamine (30 mg)

EXPERIMENTAL

Ketorolac Tromethamine - single dose (30 mg) administered intranasally (IN) for subjects weighing ≥50 kg.

Drug: Ketorolac Tromethamine

Interventions

Ketorolac Tromethamine DRUG

Single IN dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.

Ketorolac Tromethamine (15 mg)

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Egalet Ltd: lead

Study Sites (1)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Ketorolac Tromethamine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: David Bregman, M.D., Ph.D.
• Organization: Luitpold Pharmaceuticals, Inc.

dbregman@lpicrd.com

610-650-4200

Study Officials

• Lincoln Bynum, MD

  ICON Developmental Solutions

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2011
• First Posted: June 1, 2011
• Study Start: June 1, 2007
• Primary Completion: January 1, 2008
• Study Completion: May 1, 2008
• Last Updated: March 16, 2017
• Results First Posted: April 9, 2012

Record last verified: 2017-02

Locations

US (1)