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

Postoperative Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01363076
• Other study ID #: ROX 2006-02
• Status: Completed
• Phase: Phase 1
• First received: May 27, 2011
• Last updated: August 20, 2012
• Start date: June 2007
• Est. completion date: May 2008

Study information

• Verified date: August 2012
• Source: Luitpold Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 17 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Pain

Intervention

Drug:
• Ketorolac Tromethamine
Single IN dose of 15 mg ketorolac tromethamine for subjects weighing <50 kg.
• Ketorolac Tromethamine
Single IN dose of 30 mg ketorolac tromethamine for subjects weighing =50 kg.

Locations

Country	Name	City	State
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Luitpold Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No