SPRIX in 0 to 11 Year-Old Patients Undergoing Open Surgical Procedures

A Single Arm, Open Label Study of the Safety, Efficacy, and Pharmacokinetics of SPRIX (Intranasal Ketorolac Tromethamine) in 0 to 11 Year-Old Patients Undergoing Open Surgical Procedures

The purpose of this study is to evaluate the pharmacokinetics and safety of postoperative administration of SPRIX in pediatric patients (ages 0-11) undergoing open surgical procedures.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: SPRIX(intranasal ketorolac tromethamine)

Detailed Description

Evaluate the pharmacokinetics and safety of postoperative administration of SPRIX in pediatric patients (ages 0-11) undergoing open surgical procedures.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Lodz, Poland
    • Instytut "Centrum Zdrowia Matki Polki" (Institute "Mother's Memorial Hospital")
  • Lublin, Poland
    • Klinika Chirurgii i Traumatologii Dzieciecej - Dzieciecy Szpital Kliniczny im. prof. Antoniego Gebali
  • Torun, Poland
    • Regional Hospital of Ludwika Rydygiera in Torun
  • Wroclaw, Poland
    • Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu - Independent Public Clinical Hospital No. 1 in Wroclaw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 9 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients ages 0 to 11 years.
• Undergoing an open surgical procedure expected to result in at least moderate pain based on an age appropriate scale.
• Body mass index (BMI) ≤ 95th percentile of age.
• Surgical procedures that would allow the subject to likely remain in the hospital until the morning of post-operative day 3 (to complete PK sample collection).
• With parental assistance, willing and able to complete the study procedures and pain scales and to communicate meaningfully with the study personnel.
• In generally good health and capable of undergoing surgery.
• Females at risk of pregnancy were to use an acceptable form of birth control and have a negative serum or urine pregnancy test (although it is anticipated that all 0-11 year old subjects will be pre-menarchal).
• Willing to refrain from use of non-study analgesics for the duration of the study, from the day of surgery up to post-operative Day 4.
• Assents to participation and his/her parent or guardian is willing and able to sign the informed consent approved by the IRB.

Exclusion Criteria:

• Surgical procedure performed exclusively by laparoscopy.
• Known allergy or sensitivity to ketorolac, ethylene diamine tetraacetic acid (EDTA).
• Prior nasal-septal injury or surgery.
• History of peptic ulcer, gastro-esophageal reflux, or gastrointestinal bleeding.
• History of advanced renal impairment or a risk for renal failure due to volume depletion.
• Clinically significant (in the Investigator's opinion) laboratory test value outside the normal range.
• Use of either (a.) oxycodone at a dose of 30 mg/day or more or (b.) an equivalent dose of another opioid analgesic for a total of more than half of the days during the preceding month.
• The patient requires regular use (daily use in at least 25 days per month) in the 3 months prior to surgery of NSAID's , COX2 inhibitors, tramadol, or acetaminophen at daily dose of more than 2 g for the management of pain.
• Contraindication to the use of morphine, general anesthetics, bupivacaine, ropivacaine, lidocaine, other local anesthetics, muscle relaxants, hydrocodone, ondansetron, or acetaminophen (e.g., significant history of allergic reactions or intolerance to these or related substances).
• Known bleeding diathesis or other disorder or current use of agents affecting coagulation. Deep venous thrombosis prophylaxis of the surgeon's choice is permitted postoperatively.
• Current use of Central Nervous System (CNS) active drugs such as benzodiazepines, tricyclic antidepressants, or Selective Serotonin Reuptake Inhibitors (SSRIs) for pain. These drugs are permitted for non-pain indications if the dose has been stable for at least 30 days. The use of lorazepam and other sleep medications, except those containing analgesic properties, are permitted.
• Current diabetes mellitus and HbA1C > 9.5 or a history of prolonged uncontrolled diabetes.
• Use of an antihypertensive agent or diabetic regimen at a dose that has not been stable for at least 30 days.
• Any medical condition that in the investigator's opinion could adversely impact the patient's participation or safety, conduct of the study, or interfere with the pain assessments, including active infection.
• History of drug, prescription medicine, or alcohol abuse that would interfere with the subject's safety or the assessments of efficacy in this trial, in the judgement of the investigator.
• History of nasal mucosal damage or active seasonal allergies, nasal congestion or upper respiratory tract infection sufficient to interfere with intranasal drug delivery.
• Administration of an investigational product within 3 months prior to the first dose of study drug, or scheduled to receive an investigational product, while participating in the study.
• Use of Toradol (ketorolac tromethamine) in any formulation within the past 30 days prior to study entry and throughout study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SPRIX(intranasal ketorolac tromethamine); Based on subject weight

Drug: SPRIX(intranasal ketorolac tromethamine); Dose: Subjects weighing 3.0 kg received 3.15 mg (1 spray/1 nostril), subjects weighing 5.1 - 10.0 kg received 5.25 mg (1 spray/1 nostril), subjects weighing 10.1 - 15.4 kg received 10.5 mg (1 spray/1 nostril), subjects weighing 15.5 - 31.7 kg received 15.75 mg (1 spray/1 nostril), and subjects weighing >=31.8 kg received 31.5 mg (1 spray/2 nostrils). Duration of Treatment: Subjects received a dose of SPRIX every 6 hours from the day of surgery until the morning of post-operative Day 2. Dosing may have resumed after final PK assessment of the morning of post-operative Day 3 until post-operative Day 4. A follow-up phone interview took place 14 days after the final dose of study drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Blood samples will be collected for PK assessment pre-dose, at .25, .5, .75, 1, 2, and 4 hours after the first dose, at 6 hours immediately before the 2nd dose and before each of the next doses up to the dose to be administered on the morning of post operative Day 2. Blood samples will then be collected for PK assessment at 1, 2, 4, 6, 8, 12, and 24 hours after receiving the morning dose on Day 2.	Pre-dose, .25, .5, .75, 1, 2, 4, 6 hrs after the 1st dose then prior to each ensuing dose until morning of post-operative Day 2. After a single dose on morning of post-operative Day 2 PK samples will be collected @ 1, 2, 4, 6, 8, 12, & 24 hrs
Ctrough	Blood samples will be collected for PK assessment pre-dose, at .25, .5, .75, 1, 2, and 4 hours after the first dose, at 6 hours immediately before the 2nd dose and before each of the next doses up to the dose to be administered on the morning of post operative Day 2. Blood samples will then be collected for PK assessment at 1, 2, 4, 6, 8, 12, and 24 hours after receiving the morning dose on Day 2.	Pre-dose, .25, .5, .75, 1, 2, 4, 6 hrs after the 1st dose then prior to each ensuing dose until morning of post-operative Day 2. After a single dose on morning of post-operative Day 2 PK samples will be collected @ 1, 2, 4, 6, 8, 12, & 24 hrs
tmax	Blood samples will be collected for PK assessment pre-dose, at .25, .5, .75, 1, 2, and 4 hours after the first dose, at 6 hours immediately before the 2nd dose and before each of the next doses up to the dose to be administered on the morning of post operative Day 2. Blood samples will then be collected for PK assessment at 1, 2, 4, 6, 8, 12, and 24 hours after receiving the morning dose on Day 2.	Pre-dose, .25, .5, .75, 1, 2, 4, 6 hrs after the 1st dose then prior to each ensuing dose until morning of post-operative Day 2. After a single dose on morning of post-operative Day 2 PK samples will be collected @ 1, 2, 4, 6, 8, 12, & 24 hrs

Collaborators and Investigators

• Sponsor: Egalet Ltd
• Investigators: Study Director: Linda M. Mundy, MD, PhD, American Regent, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: March 31, 2014
• First Submitted That Met QC Criteria: March 31, 2014
• First Posted (Estimate): April 3, 2014

Study Record Updates

• Last Update Posted (Actual): March 17, 2017
• Last Update Submitted That Met QC Criteria: March 15, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Post operative pain management
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac; Ketorolac Tromethamine
• Other Study ID Numbers: 1SPR11002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided