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

Phase 1

Completed

Conditions: Postoperative Pain

Interventions: Drug: Ketorolac Tromethamine

Registration Number: NCT01363076

Lead Sponsor: Egalet Ltd

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ketorolac Tromethamine (30 mg)	Ketorolac Tromethamine	Ketorolac Tromethamine - single dose (30 mg) administered intranasally (IN) for subjects weighing ≥50 kg.
Ketorolac Tromethamine (15 mg)	Ketorolac Tromethamine	Ketorolac Tromethamine - single dose (15 mg) administered intranasally (IN) for subjects weighing \<50 kg.

Primary Outcome Measures

Name	Time	Method
Cmax (the Maximum Observed Plasma Concentration)	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.
Tmax (The Time to Maximum Observed Plasma Concentration; ie. The Time at Which Cmax Occured)	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.
AUClast (the Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Quantifiable Timepoint Post-dose)	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.
AUCinf (the AUC Time From Zero to Infinity, Where Possible)	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).
AUC 0-24 (the AUC From Time Zero to 24 Hours Post-dose	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.
t1/2 (the Terminal Half-life, Where Possible)	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.
MRT (Mean Residence Time)	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.