Moderate-severe PainPhase 4NCT02101554

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

A Phase 4 study testing Ages 7-11 and ages 12-17 in people with Moderate-severe Pain, run by Pfizer at 19 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 7 to 17 years
Conditions the study is for: Moderate-severe Pain
What is being tested?: Ages 7-11 and ages 12-17
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 19 sitesUnited States
Study dates: 24 Apr 2015to 26 Jun 2019
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 7 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

19 sites in 1 country.

City, postcode or hospital

19 sites in 1 country

United States19 sites

University of Illinois at Chicago Clinical Research Center
Chicago, Illinois, 60612
University of Illinois at the Med Center, University of Illinois
Chicago, Illinois, 60612
University of Illinois Hospital and Health Sciences System
Chicago, Illinois, 60612
East Carolina University Brody School of Medicine(ECU)
Greenville, North Carolina, 27834
Leo Jenkins Cancer Center Pharmacy Attn: Rebecca Turnage
Greenville, North Carolina, 27834
Gottschalk Medical Plaza
Irvine, California, 92697
Children's Hospital Los Angeles
Los Angeles, California, 90027
Holtz Children Hospital/Jackson Memorial Hospital
Miami, Florida, 33136
Jackson Memorial Hospital - Pharmacy Department Basement West
Miami, Florida, 33136
Sylvester Comprehensive Cancer Center-Alex's Place
Miami, Florida, 33136
University of Miami / Jackson Memorial Hospital
Miami, Florida, 33136
Nicklaus Children's Hospital
Miami, Florida, 33155
Veritas Research Corp.
Miami Lakes, Florida, 33014
The University of California, Irvine Health - Medical Specialties
Orange, California, 92868
UCI Medical Center- Outpatient Pharmacy
Orange, California, 92868
University of California, Irvine Health-Inpatient Pharmacy
Orange, California, 92868
University of California, Irvine Health-Medical Specialties
Orange, California, 92868
Primary Children's Hospital Outpatient Services
Salt Lake City, Utah, 84113
Primary Children's Hospital
Salt Lake City, Utah, 84113

Other trials in United States

About this study

Official title: AN OPEN-LABEL STUDY TO EVALUATE THE SAFETY AND PHARMACOKINETICS OF PF-06412528 IN CHILDREN 7-17 YEARS FOR THE TREATMENT OF MODERATE-TO-SEVERE PAIN

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.

Read the detailed description

Subjects, once stabilized to Embeda, need only complete a minimum of 2 of the 6 week study duration to satisfy the PK endpoint. A safety follow-up visit is required at 1 week post-last dose.

Conditions: Moderate-severe Pain
Being tested: Ages 7-11, ages 12-17
Keywords: Pediatric, pain indication, controlled release morphine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ages 7-11Drug
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.
ages 12-17Drug
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.

Study groups in NCT02101554
Study group	Role	What they receive
Embeda	Experimental	One arm, open label, active Receives: Drug: Ages 7-11; Drug: ages 12-17

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: Anytime post-dose on Visit 4 (Week 4)

Secondary outcomes (4)

Number of Participants With Pre-defined Criteria of Vital Signs
Pre-defined criteria of vital signs included supine diastolic blood pressure (DBP) change from baseline greater than or equal to (>=) 20 millimeter of mercury (mmHg): increase and decrease; supine systolic blood pressure (SBP) change from baseline >=30 mmHg: increase and decrease.
Measured: Week 1 up to Week 10
Number of Participants With Laboratory Test Abnormalities
Laboratory parameters included: hematology (hemoglobin: <0.8*LLN, hematocrit: <0.8*LLN, red blood cell: <0.8* LLN, platelet <0.5*LLN; >1.75*ULN and white blood cell count <0.6*LLN, neutrophils <0.8* LLN, eosinophils >1.2*ULN, monocytes >1.2*ULN, basophils >1.2*ULN and lymphocytes <0.8* LLN), chemistry (blood urea nitrogen >1.3*ULN, creatinine>1.3*ULN, sodium <0.95*LLN, potassium <0.9*LLN, >1.1*ULN, aspartate aminotransferase >3.0*ULN, alanine aminotransferase >3.0*ULN, total bilirubin >1.5*ULN, alkaline phosphatase >3.0*ULN, albumin <0.8*LLN, total protein<0.8*LLN, >1.2*ULN, Albumin <0.8*LLN, Blood Urea Nitrogen >1.3*ULN, Creatinine >1.3*ULN, HDL Cholesterol <0.8*LLN, Chloride <0.9*LLN, Phosphate <0.8*LLN, Bicarbonate <0.9*LLN, Glucose <0.6*LLN, Creatine Kinase >2.0*ULN, Urobilinogen >=1) and urinalysis (specific gravity <1.003, pH <4.5 urine glucose >=1, ketones >=1 urine protein >=1, urine bilirubin >=1, nitrite >=1, urine leukocytes >=20).
Measured: Week 1 up to Week 10
Apparent Volume of Distribution (Vz/F) of PF-06412528
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Measured: Anytime post-dose on Visit 4 (Week 4)
Dose-Exposure Relationship of Metabolites of Morphine, Naltrexone and 6-β-Naltrexol
Measured: Anytime post-dose on Visit 4 (Week 4)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Apr 201526 Jun 2019

First posted2 Apr 2014 (estimated)
Study start24 Apr 2015
Primary completion26 Jun 2019
Study completion26 Jun 2019

Why it stopped: Pfizer released from post-marketing commitment and study terminated because too few patients in the age group; not because of efficacy or safety issues.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Moderate-severe PainStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Masking: None (open label)
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02101554
Sponsor's protocol ID: B4541006
Other IDs: EMBEDA
Status last verified: Jun 2020
First submitted: 5 Mar 2014
Last updated: 10 Jul 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 10 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: AN OPEN-LABEL STUDY TO EVALUATE THE SAFETY AND PHARMACOKINETICS OF PF-06412528 IN CHILDREN 7-17 YEARS FOR THE TREATMENT OF MODERATE-TO-SEVERE PAIN
ClinicalTrials.gov ID: NCT02101554
Acronym / sponsor ID: B4541006
Conditions: Moderate-severe Pain
Keywords: Pediatric, pain indication, controlled release morphine
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Pfizer released from post-marketing commitment and study terminated because too few patients in the age group; not because of efficacy or safety issues.
Enrolment: 19 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: 24 Apr 2015 (actual)
Primary completion: 26 Jun 2019 (actual)
Study completion: 26 Jun 2019 (actual)
First posted: 2 Apr 2014 (estimated)
Results: Posted 10 Jul 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Detailed description

Subjects, once stabilized to Embeda, need only complete a minimum of 2 of the 6 week study duration to satisfy the PK endpoint. A safety follow-up visit is required at 1 week post-last dose.

Study design

Primary purpose: Treatment
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Embeda	Experimental	Drug: Ages 7-11, Drug: ages 12-17One arm, open label, active

Who may qualify

Ages: 7 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (2 listed)

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.

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ages 7-11Oral/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.	Drug	Embeda
ages 12-17Oral/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.	Drug	Embeda

Primary outcome

Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 1 to Week 4
Time frame: 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.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 5 to Week 10
Time frame: 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.
Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4
Time frame: 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.
Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10
Time frame: 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.
Number of Participants With Treatment Emergent Treatment Related Adverse Events: Week 1 to Week 4
Time frame: 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.
Number of Participants With Treatment Emergent Treatment Related Adverse Events: Week 5 to Week 10
Time frame: 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening Before Day 1
Time frame: At Screening (2 weeks before Day 1 of study)
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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1
Time frame: Day 1 (Pre-dose)
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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1
Time frame: 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 2
Time frame: 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 3
Time frame: 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 4
Time frame: 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 4
Time frame: Early Termination before Week 4 (anytime between Week 1 to 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening on Week 5
Time frame: Screening before treatment started at 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 of Week 5
Time frame: 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 6
Time frame: 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8
Time frame: 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 10
Time frame: 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10
Time frame: Early Termination before Week 10 (anytime between Week 5 to 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.
Apparent Oral Clearance (CL/F) of PF-06412528
Time frame: Anytime post-dose on Visit 4 (Week 4)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Average Concentration at Steady-state (Css, av) of PF-06412528
Time frame: Anytime post-dose on Visit 4 (Week 4)
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).

4 secondary outcomes

Number of Participants With Pre-defined Criteria of Vital Signs
Time frame: Week 1 up to Week 10
Number of Participants With Laboratory Test Abnormalities
Time frame: Week 1 up to Week 10
Apparent Volume of Distribution (Vz/F) of PF-06412528
Time frame: Anytime post-dose on Visit 4 (Week 4)
Dose-Exposure Relationship of Metabolites of Morphine, Naltrexone and 6-β-Naltrexol
Time frame: Anytime post-dose on Visit 4 (Week 4)

Results and safety

Results posted to the registry on 10 Jul 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PF-06412528 <=20 mg	6	3
PF-06412528 >20-40 mg	10	5
PF-06412528 >40-80 mg	3	2

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

Time frame: Week 1 to Week 4. Count of participants. Unit: Participants

Measure	PF-06412528 <=20 mg n = 6	PF-06412528 >20-40 mg n = 10	PF-06412528 >40-80 mg n = 3
AEs	4	9	3
SAEs	1	1	1

Population analysed: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 1 to Week 4.

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

Time frame: Week 5 to Week 10. Count of participants. Unit: Participants

Measure	PF-06412528 <=20 mg n = 4	PF-06412528 >20-40 mg n = 8	PF-06412528 >40-80 mg n = 2
AEs	3	7	2
SAEs	1	2	1

Population analysed: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 5 to Week 10.

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

Time frame: Week 1 to Week 4. Count of participants. Unit: Participants

Measure	PF-06412528 <=20 mg n = 6	PF-06412528 >20-40 mg n = 10	PF-06412528 >40-80 mg n = 3
Mild	1	4	2
Moderate	0	3	0
Severe	3	2	1

Population analysed: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 1 to Week 4.

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

Time frame: Week 5 to Week 10. Count of participants. Unit: Participants

Measure	PF-06412528 <=20 mg n = 4	PF-06412528 >20-40 mg n = 8	PF-06412528 >40-80 mg n = 2
Mild	1	3	0
Moderate	1	2	0
Severe	1	2	2

Population analysed: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 5 to Week 10.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Week 1 up to Week 11 (including 1 week of follow-up). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PF-06412528 <=20 mg	2 of 6 (33.3%)	5 of 6 (83.3%)	0 of 6
PF-06412528 >20-40 mg	2 of 10 (20%)	9 of 10 (90%)	0 of 10
PF-06412528 >40-80 mg	2 of 3 (66.7%)	3 of 3 (100%)	0 of 3

Limitations and caveats (from the sponsor): Data for pharmacokinetic outcome measures was not collected, as there were insufficient pharmacokinetic samples due to early termination of the study by the sponsor.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

19 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ages 7-11 and ages 12-17 in people with Moderate-severe Pain, run by Pfizer at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 1 to Week 4 (time frame: Week 1 to Week 4). The study lists 21 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02101554.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2020.