Safety and Pharmacokinetic Study of EMBEDA in Children Ages 7-17 With Pain

NCT02101554 | Terminated Phase 4 Results FDA Drug

• 2 other identifiers: B4541006EMBEDA
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 19

Brief Summary

Safety and pharmacokinetics of an abuse-deterrent, extended-release formulation of morphine sulfate with a sequestered naltrexone core in children 7-17 with moderate-severe pain.

Conditions

Moderate-severe Pain

Keywords

Pediatric; pain indication; controlled release morphine

Outcome Measures

Primary Outcomes (21)

• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 1 to Week 4

  An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious adverse events.

  Week 1 to Week 4

• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 5 to Week 10

  An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious adverse events.

  Week 5 to Week 10

• Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4

  An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity; mild (does not interfere with participant's usual function), moderate (interferes to some extent with participant's usual function) and severe (interferes significantly with participant's usual function).A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious adverse events.

  Week 1 to Week 4

• Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10

  An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity; mild (does not interfere with participant's usual function), moderate (interferes to some extent with participant's usual function) and severe (interferes significantly with participant's usual function). A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious adverse events.

  Week 5 to Week 10

• Number of Participants With Treatment Emergent Treatment Related Adverse Events: Week 1 to Week 4

  An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. Relatedness to PF-06412528 was assessed by the investigator.

  Week 1 to Week 4

• Number of Participants With Treatment Emergent Treatment Related Adverse Events: Week 5 to Week 10

  An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. Relatedness to PF-06412528 was assessed by the investigator.

  Week 5 to Week 10

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening Before Day 1

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  At Screening (2 weeks before Day 1 of study)

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  Day 1 (Pre-dose)

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  Week 1

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 2

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  Week 2

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 3

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  Week 3

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 4

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  Week 4

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 4

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  Early Termination before Week 4 (anytime between Week 1 to Week 4)

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening on Week 5

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  Screening before treatment started at Week 5

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 of Week 5

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  Day 1 of Week 5

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 6

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  Week 6

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  Week 8

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 10

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  Week 10

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10

  COWS is a clinician-administered instrument, to assess participants' clinical opiate withdrawal level. The scale ranges from 0 (none symptoms) to 48 (severe symptoms), higher score = more severe withdrawal. Scores category: 0 to 4 = none to minimal, 5 to 12 = mild, 13 to 24 = moderate, 25 to 36 = moderately severe withdrawal and 37 to 48 = severe withdrawal. Participants experiencing a COWS score greater than equal to (\>=) 13 is treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. In this outcome measure, participants as per COWS score categories are reported. Only those COWS categories are presented which had at least 1 participant for any reporting arm.

  Early Termination before Week 10 (anytime between Week 5 to Week 10)

• Apparent Oral Clearance (CL/F) of PF-06412528

  Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

  Anytime post-dose on Visit 4 (Week 4)

• Average Concentration at Steady-state (Css, av) of PF-06412528

  Css, av was defines as the average steady state concentration of a drug ("steady state" has been achieved when the rate of drug administration and the rate of drug elimination are equal).

  Anytime post-dose on Visit 4 (Week 4)

Secondary Outcomes (4)

• Number of Participants With Pre-defined Criteria of Vital Signs

  Week 1 up to Week 10

• Number of Participants With Laboratory Test Abnormalities

  Week 1 up to Week 10

• Apparent Volume of Distribution (Vz/F) of PF-06412528

  Anytime post-dose on Visit 4 (Week 4)

• Dose-Exposure Relationship of Metabolites of Morphine, Naltrexone and 6-β-Naltrexol

  Anytime post-dose on Visit 4 (Week 4)

Study Arms (1)

Embeda

EXPERIMENTAL

One arm, open label, active

Drug: Ages 7-11; Drug: ages 12-17

Interventions

Ages 7-11 DRUG

Oral/Capsule, once per day or twice per day dosing; Treatment duration consists of a 1 to 4 week Conversion/Titration Phase leading to a 2 to 6 week Maintenance Treatment duration.

Embeda

ages 12-17 DRUG

Oral/Capsule, once per day or twice per day dosing; Treatment duration consists of a 1 to 4 week Conversion/Titration Phase leading to a 2 to 6 week Maintenance Treatment duration.

Embeda

Eligibility Criteria

• Age: 7 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children 7-17 with moderate to severe pain requiring around the clock treatment with an opioid analgesic.
• Be an experienced opioid user, defined as any subject treated with opioid therapy, equivalent or equal to \>20 mg per day of morphine, for a period of 3 consecutive days immediately prior to first day of dosing.

You may not qualify if:

• Columbia-Suicide Severity Rating Scale (C-SSRS) for suicidal ideation and behavior in past year.
• Hypersensitivity to morphine, naltrexone.
• A life expectancy (assessed by investigator) of less than 6 months or is no longer capable of taking medication orally.
• Undergone surgery within 3 days prior to the first day of dosing.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (19)

Gottschalk Medical Plaza

Irvine, California, 92697, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

The University of California, Irvine Health - Medical Specialties

Orange, California, 92868, United States

Location

UCI Medical Center- Outpatient Pharmacy

Orange, California, 92868, United States

Location

University of California, Irvine Health-Inpatient Pharmacy

Orange, California, 92868, United States

Location

University of California, Irvine Health-Medical Specialties

Orange, California, 92868, United States

Location

Holtz Children Hospital/Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Jackson Memorial Hospital - Pharmacy Department Basement West

Miami, Florida, 33136, United States

Location

Sylvester Comprehensive Cancer Center-Alex's Place

Miami, Florida, 33136, United States

Location

University of Miami / Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Veritas Research Corp.

Miami Lakes, Florida, 33014, United States

Location

University of Illinois at Chicago Clinical Research Center

Chicago, Illinois, 60612, United States

Location

University of Illinois at the Med Center, University of Illinois

Chicago, Illinois, 60612, United States

Location

University of Illinois Hospital and Health Sciences System

Chicago, Illinois, 60612, United States

Location

East Carolina University Brody School of Medicine(ECU)

Greenville, North Carolina, 27834, United States

Location

Leo Jenkins Cancer Center Pharmacy Attn: Rebecca Turnage

Greenville, North Carolina, 27834, United States

Location

Primary Children's Hospital Outpatient Services

Salt Lake City, Utah, 84113, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

Limitations and Caveats

Data for pharmacokinetic outcome measures was not collected, as there were insufficient pharmacokinetic samples due to early termination of the study by the sponsor.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2014
• First Posted: April 2, 2014
• Study Start: April 24, 2015
• Primary Completion: June 26, 2019
• Study Completion: June 26, 2019
• Last Updated: July 10, 2020
• Results First Posted: July 10, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share

Locations

US (19)