Safety and Clinical Utility Study of SSEC Fentanyl 40 mcg for Acute Post-op Pain Management in Pediatric Participants

• ClinicalTrials.gov Identifier: NCT02395653
• Recruitment Status: Completed
• First Posted: March 23, 2015
• Results First Posted: September 18, 2017
• Last Update Posted: October 26, 2017
• Sponsor: The Medicines Company
• Collaborator: Incline Therapeutics, Inc.
• Information provided by (Responsible Party): The Medicines Company

Study Description

Brief Summary:

The objective of this study is to evaluate the safety and clinical utility of the active, SSEC fentanyl 40 micrograms (mcg) for the management of acute, postoperative pain in pediatric participants.

Condition or disease	Intervention/treatment	Phase
Pain, Postoperative	Drug: fentanyl	Phase 3

Detailed Description:

An open label evaluation of the safety and clinical utility of the active, SSEC fentanyl 40 mcg for the management of acute postoperative pain in pediatric participants 12 to less than 18 years of age.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 71 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: An Open Label Evaluation of the Safety and Clinical Utility of the Active, Separated System With Enhanced Controller (SSEC) Fentanyl 40 mcg for the Management of Acute Postoperative Pain in Pediatric Patients 12 to Less Than 18 Years of Age
• Actual Study Start Date: June 29, 2015
• Actual Primary Completion Date: September 12, 2016
• Actual Study Completion Date: September 12, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: SSEC Fentanyl; SSEC fentanyl iontophoretic transdermal system, 40 mcg fentanyl per activation.	Drug: fentanyl; An opioid that has been administered parenterally as an anesthetic and analgesic for more than 20 years.; Other Name: IONSYS

Outcome Measures

Primary Outcome Measures :

1. Assessment Of Participant's Ability To Use The SSEC [ Time Frame: Completed at the time of the participant's termination of study treatment (up to 72 hours after study drug administration) ]
   Investigator's assessment of participant's ability to use the SSEC system safely and effectively. The assessment consisted of a 4-level categorical evaluation (poor, fair, good, and excellent). Because of the descriptive nature of this study, no formal statistical hypothesis testing was performed.
2. Assessment Of Adherence Of The SSEC System To Skin [ Time Frame: Immediately prior to removal at each 24-hour time point, or at early withdrawal, for up to 3 consecutive days (up to 72 hours) ]
   The adhesion of each SSEC was evaluated immediately prior to removal at each 24-hour time point, or at early withdrawal. Adhesion was recorded using the following classification: System adhered to at least 90% of the application area with no edges unattached; System adhered between 75% and 89%; System was <75% adhered and not taped; System was secured with tape. The number of SSEC systems for all time points in each category is presented. Because of the descriptive nature of this study, no formal statistical hypothesis testing was performed.

Secondary Outcome Measures :

1. Change From Baseline To 1 Hour And 24 Hours In Skin Irritation Score After SSEC Removal [ Time Frame: Baseline, 1 hour and 24 hours after SSEC removal. ]
   Skin irritation at the SSEC application site was to be assessed immediately prior to placement of the study system and at 1 and 24 hours after removal of each study system. The application site was to be scored using the following scale: 0=No evidence of irritation; 1=Minimal erythema, barely perceptible; 2=Definite erythema, readily visible, minimal edema, or minimal papular response; 3=Erythema and papules; 4=Definite edema; 5=Erythema, edema, and papules; 6=Vesicular eruption; 7=Strong reaction spreading beyond the application site.
2. Number Of Participants To Experience Clinically Relevant Respiratory Depression (CRRD) [ Time Frame: From the time of application of the first system through 7 days following end of study drug administration. ]
   Respiratory function and occurrence of CRRD was defined as simultaneous occurrence of bradypnoea (respiratory rate <10 breaths per minute for participants 9-15 years of age and sustained for 1 minute, or <8 breaths per minute for participants 16-17 years of age), with excessive sedation (that is, the participant is not easily aroused).

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Participants whose parent(s) or guardian(s) have/has signed and dated an informed consent form for the participant to participate in the study, or participants who have provided written assent to participate in the study
• Male or female inpatients, age 12 to <18 years of age inclusive on the day of surgery
• Participants capable of understanding and cooperating with the requirements of the study, including being able to report their pain intensity using the 11-point Numeric Rating Scale and operate the SSEC
• American Society of Anesthesiologists physical status I, II or III
• Body weight of at least 40.0 kilogram (kg)
• Postoperative participants who have undergone general or regional anesthesia for abdominal, pelvic/genitourinary, orthopedic, or thoracic surgery
• Postoperative participants who have been observed during recovery and are expected to remain hospitalized and have pain requiring parenteral opioids (that is, intravenous [IV] patient-controlled anesthesia) for the next 24 hours or longer
• Participants who are awake and breathing spontaneously with a respiratory rate of 14 to 18 breaths per minute, peripheral capillary oxygen saturation ≥93% (with or without supplemental oxygen), and able to answer questions and follow commands
• Participants who have been observed during recovery, who are awake, able to answer questions and follow commands, and who have been comfortable for at least 30 minutes, with a pain intensity score ≤4 (numeric rating scale 0-10), with or without titration to comfort with IV opioids

Exclusion Criteria:

• Participants who have undergone any surgery on the airway, head, or neck
• Participants who received an extended-release opioid within 48 hours prior to Hour 0 or who are expected to have postoperative analgesia supplied by a continuous regional technique or participant-controlled epidural analgesia
• Participants with a history of allergy or hypersensitivity to fentanyl, skin adhesives, and/or cetylpyridinium chloride
• Participants who are expected to require intensive care or will likely require additional surgical procedures within 36 hours
• Participants who received intra-operative and/or postoperative administration of opioids other than morphine, hydromorphone, fentanyl, sufentanil, or alfentanil. Exception: If there are no medical contraindications, meperidine (pethidine) up to 0.5 milligram/kg IV is permitted during recovery for shivering
• Participants who require airway support (nasal or oropharyngeal airway intubation, or laryngeal mask airway at the time of final baseline assessments (that is, at the time of IONSYS application [Hour 0])
• Participants who are known or suspected to be opioid tolerant, have a history of opioid dependence within 3 months before the start of the study, or who are known to have used illicit drugs or alcohol within 14 days of the start of the study
• Participants with active generalized skin disorders or active local skin disease that precludes SSEC application to the chest or upper arm
• Participants with any coexisting major medical conditions that are likely to interfere with study procedures including, but not limited to, psychiatric conditions, chronic depression, suicidal ideation, autism
• Positive pregnancy test for any female

Contacts and Locations

Locations

United States, California

Packard Children's Hospital at Stanford

Palo Alto, California, United States, 94304

United States, Florida

University of Miami/Jackson Memorial Hospital

Miami, Florida, United States, 33136

United States, Georgia

Children's Healthcare of Atlanta

Atlanta, Georgia, United States, 30342

United States, Maryland

Johns Hopkins Hospital, Charlotte R. Bloomberg Children's Center

Baltimore, Maryland, United States, 21287

United States, Missouri

St. Louis Children's Hospital

Saint Louis, Missouri, United States, 63110

United States, Pennsylvania

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States, 15224

United States, Texas

Children's Medical Center of Dallas

Dallas, Texas, United States, 75235

United States, Washington

Harborview Medical Center

Seattle, Washington, United States, 98104

United States, Wisconsin

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

The Medicines Company

Incline Therapeutics, Inc.

Investigators

• Principal Investigator: Elliot J Krane, MD; Stanford Children's Health

More Information

Publications:

Chelly JE, Grass J, Houseman TW, Minkowitz H, Pue A. The safety and efficacy of a fentanyl patient-controlled transdermal system for acute postoperative analgesia: a multicenter, placebo-controlled trial. Anesth Analg. 2004 Feb;98(2):427-433. doi: 10.1213/01.ANE.0000093314.13848.7E.

Grond S, Hall J, Spacek A, Hoppenbrouwers M, Richarz U, Bonnet F. Iontophoretic transdermal system using fentanyl compared with patient-controlled intravenous analgesia using morphine for postoperative pain management. Br J Anaesth. 2007 Jun;98(6):806-15. doi: 10.1093/bja/aem102. Erratum In: Br J Anaesth. 2008 Jan;100(1):146.

Hartrick CT, Bourne MH, Gargiulo K, Damaraju CV, Vallow S, Hewitt DJ. Fentanyl iontophoretic transdermal system for acute-pain management after orthopedic surgery: a comparative study with morphine intravenous patient-controlled analgesia. Reg Anesth Pain Med. 2006 Nov-Dec;31(6):546-54. doi: 10.1016/j.rapm.2006.08.011.

Minkowitz HS, Rathmell JP, Vallow S, Gargiulo K, Damaraju CV, Hewitt DJ. Efficacy and safety of the fentanyl iontophoretic transdermal system (ITS) and intravenous patient-controlled analgesia (IV PCA) with morphine for pain management following abdominal or pelvic surgery. Pain Med. 2007 Nov-Dec;8(8):657-68. doi: 10.1111/j.1526-4637.2006.00257.x.

Minkowitz HS, Yarmush J, Donnell MT, Tonner PH, Damaraju CV, Skowronski RJ. Safety and tolerability of fentanyl iontophoretic transdermal system: findings from a pooled data analysis of four clinical trials. J Opioid Manag. 2010 May-Jun;6(3):203-10. doi: 10.5055/jom.2010.0018.

Viscusi ER, Reynolds L, Chung F, Atkinson LE, Khanna S. Patient-controlled transdermal fentanyl hydrochloride vs intravenous morphine pump for postoperative pain: a randomized controlled trial. JAMA. 2004 Mar 17;291(11):1333-41. doi: 10.1001/jama.291.11.1333.

Viscusi ER, Reynolds L, Tait S, Melson T, Atkinson LE. An iontophoretic fentanyl patient-activated analgesic delivery system for postoperative pain: a double-blind, placebo-controlled trial. Anesth Analg. 2006 Jan;102(1):188-94. doi: 10.1213/01.ane.0000183649.58483.77.

Viscusi ER, Siccardi M, Damaraju CV, Hewitt DJ, Kershaw P. The safety and efficacy of fentanyl iontophoretic transdermal system compared with morphine intravenous patient-controlled analgesia for postoperative pain management: an analysis of pooled data from three randomized, active-controlled clinical studies. Anesth Analg. 2007 Nov;105(5):1428-36, table of contents. doi: 10.1213/01.ane.0000281913.28623.fd.

• Responsible Party: The Medicines Company
• ClinicalTrials.gov Identifier: NCT02395653
• Other Study ID Numbers: PD2013-002; 2014-002405-37 ( EudraCT Number )
• First Posted: March 23, 2015
• Results First Posted: September 18, 2017
• Last Update Posted: October 26, 2017
• Last Verified: September 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by The Medicines Company:

Pediatric; Postoperative; Pain Management

Additional relevant MeSH terms:

Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Fentanyl; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adjuvants, Anesthesia; Anesthetics, Intravenous; Anesthetics, General; Anesthetics