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

• Sponsor: The Medicines Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02395653
• Collaborator: Incline Therapeutics, Inc. (Industry)
• Enrollment: 71
• Locations: 10
• Arm: 1
• Actual Duration (Months): 14.5
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.5

Study Details

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
• 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: Jun 29, 2015
• Actual Primary Completion Date: Sep 12, 2016
• Actual Study Completion Date: Sep 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 Names: IONSYS

Outcome Measures

Primary Outcome Measures

1. Assessment Of Participant's Ability To Use The SSEC [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 [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 [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) [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

Criteria

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

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

	Site	City	State	Country	Postal Code
1	Packard Children's Hospital at Stanford	Palo Alto	California	United States	94304
2	University of Miami/Jackson Memorial Hospital	Miami	Florida	United States	33136
3	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30342
4	Johns Hopkins Hospital, Charlotte R. Bloomberg Children's Center	Baltimore	Maryland	United States	21287
5	St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
6	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
7	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
8	Children's Medical Center of Dallas	Dallas	Texas	United States	75235
9	Harborview Medical Center	Seattle	Washington	United States	98104
10	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

Study Documents (Full-Text)

None provided.

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. 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.
• 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.
• 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.
• 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.
• 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.
• 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.

• Responsible Party: The Medicines Company
• ClinicalTrials.gov Identifier: NCT02395653
• Other Study ID Numbers: PD2013-002; 2014-002405-37
• First Posted: Mar 23, 2015
• Last Update Posted: Oct 26, 2017
• Last Verified: Sep 1, 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; Fentanyl

Study Results

Participant Flow

Recruitment Details	Pediatric participants from 12 to less than 18 years of age who had undergone general or regional anesthesia for elective abdominal, pelvic/genitourinary, orthopedic, or thoracic surgery.
Pre-assignment Detail	Screening within 3 weeks of study start included review of inclusion/exclusion criteria, informed consent signature, medical history, height, weight, vital signs, American Society of Anesthesiologists physical status, and a review of the Separated System With Enhanced Controller (SSEC) for delivery of 40 micrograms (mcg) fentanyl/dose.

Arm/Group Title	SSEC Fentanyl
Arm/Group Description	Post-surgery, participants received fentanyl via the active IONSYS® SSEC fentanyl iontophoretic transdermal system that provided on-demand systemic delivery of 40 mcg fentanyl per dose for up to 24 hours, or a maximum of 80 doses, whichever came first, for up to 3 consecutive days (up to 72 hours).
Period Title: Overall Study
STARTED	71
Received at Least 1 Dose of Study Drug	61
COMPLETED	59
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	SSEC Fentanyl
Arm/Group Description	Post-surgery, participants received fentanyl via the active IONSYS® SSEC fentanyl iontophoretic transdermal system that provided on-demand systemic delivery of 40 mcg fentanyl per dose for up to 24 hours, or a maximum of 80 doses, whichever came first, for up to 3 consecutive days (up to 72 hours).
Overall Participants	61
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.7 (1.54)
Sex: Female, Male (Count of Participants)
Female	45 73.8%
Male	16 26.2%

Outcome Measures

1. Primary Outcome

Title	Assessment Of Participant's Ability To Use The SSEC
Description	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.
Time Frame	Completed at the time of the participant's termination of study treatment (up to 72 hours after study drug administration)

Outcome Measure Data

Analysis Population Description

The Evaluable Population consists of all participants who received fentanyl from the SSEC for at least 3 hours.

Arm/Group Title	SSEC Fentanyl
Arm/Group Description	Post-surgery, participants received fentanyl via the active IONSYS® SSEC fentanyl iontophoretic transdermal system that provided on-demand systemic delivery of 40 mcg fentanyl per dose for up to 24 hours, or a maximum of 80 doses, whichever came first, for up to 3 consecutive days (up to 72 hours).
Measure Participants	61
Poor	1 1.6%
Fair	2 3.3%
Good	10 16.4%
Excellent	48 78.7%
Missing	0 0%

2. Primary Outcome

Title	Assessment Of Adherence Of The SSEC System To Skin
Description	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.
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)

Outcome Measure Data

Analysis Population Description

The Evaluable Population consists of all participants who received fentanyl from the SSEC for at least 3 hours.

Arm/Group Title	SSEC Fentanyl
Arm/Group Description	Post-surgery, participants received fentanyl via the active IONSYS® SSEC fentanyl iontophoretic transdermal system that provided on-demand systemic delivery of 40 mcg fentanyl per dose for up to 24 hours, or a maximum of 80 doses, whichever came first, for up to 3 consecutive days (up to 72 hours).
Measure Participants	61
Measure SSEC systems used by 61 participants	107
≥90% of area with no edges unattached	97
75% to 89%	6
<75% adhered and not taped	3
System was secured with tape	1
Not assessed	0

3. Secondary Outcome

Title	Change From Baseline To 1 Hour And 24 Hours In Skin Irritation Score After SSEC Removal
Description	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.
Time Frame	Baseline, 1 hour and 24 hours after SSEC removal.

Outcome Measure Data

Analysis Population Description

The Evaluable Population consists of all participants who received fentanyl from the SSEC for at least 3 hours.

Arm/Group Title	SSEC Fentanyl
Arm/Group Description	Post-surgery, participants received fentanyl via the active IONSYS® SSEC fentanyl iontophoretic transdermal system that provided on-demand systemic delivery of 40 mcg fentanyl per dose for up to 24 hours, or a maximum of 80 doses, whichever came first, for up to 3 consecutive days (up to 72 hours).
Measure Participants	61
System 1, Hour 1	1.1 (0.94)
System 1, Hour 24	1.8 (1.43)
System 2, Hour 1	1.0 (0.61)
System 2, Hour 24	1.6 (1.33)
System 3, Hour 1	1.0 (1.22)
System 3, Hour 24	0.8 (1.26)

4. Secondary Outcome

Title	Number Of Participants To Experience Clinically Relevant Respiratory Depression (CRRD)
Description	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).
Time Frame	From the time of application of the first system through 7 days following end of study drug administration.

Outcome Measure Data

Analysis Population Description

The Evaluable Population consists of all participants who received fentanyl from the SSEC for at least 3 hours.

Arm/Group Title	SSEC Fentanyl
Arm/Group Description	Post-surgery, participants received fentanyl via the active IONSYS® SSEC fentanyl iontophoretic transdermal system that provided on-demand systemic delivery of 40 mcg fentanyl per dose for up to 24 hours, or a maximum of 80 doses, whichever came first, for up to 3 consecutive days (up to 72 hours).
Measure Participants	61
Bradypnoea	0 0%
Excessive Sedation	0 0%
Simultaneous Bradypnoea and Excessive Sedation	0 0%

Adverse Events

Time Frame	Adverse events were collected from the time of application of the first system through 7 days following the end of study drug administration.
Arm/Group Title	SSEC Fentanyl
Arm/Group Description	Post-surgery, participants received fentanyl via the active IONSYS® SSEC fentanyl iontophoretic transdermal system that provided on-demand systemic delivery of 40 mcg fentanyl per dose for up to 24 hours, or a maximum of 80 doses, whichever came first, for up to 3 consecutive days (up to 72 hours).
All Cause Mortality
	SSEC Fentanyl
	Affected / at Risk (%)	# Events
Total	0/61 (0%)
Serious Adverse Events
	SSEC Fentanyl
	Affected / at Risk (%)	# Events
Total	1/61 (1.6%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/61 (1.6%)	1
Other (Not Including Serious) Adverse Events
	SSEC Fentanyl
	Affected / at Risk (%)	# Events
Total	44/61 (72.1%)
Gastrointestinal disorders
Vomiting	19/61 (31.1%)	23
Nausea	18/61 (29.5%)	19
Constipation	11/61 (18%)	11
General disorders
Application site erythema	10/61 (16.4%)	10
Application site papules	10/61 (16.4%)	10
Pyrexia	7/61 (11.5%)	7
Nervous system disorders
Dizziness	7/61 (11.5%)	9
Skin and subcutaneous tissue disorders
Pruritus generalised	5/61 (8.2%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.