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.
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 Type
INTERVENTIONAL
Purpose
TREATMENT
Masking
NONE
Enrollment
19
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.
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.
Gottschalk Medical Plaza
Irvine, California, United States
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.
Time frame: 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.
Time frame: 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.
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Children's Hospital Los Angeles
Los Angeles, California, United States
The University of California, Irvine Health - Medical Specialties
Orange, California, United States
UCI Medical Center- Outpatient Pharmacy
Orange, California, United States
University of California, Irvine Health-Inpatient Pharmacy
Orange, California, United States
University of California, Irvine Health-Medical Specialties
Orange, California, United States
Holtz Children Hospital/Jackson Memorial Hospital
Miami, Florida, United States
Jackson Memorial Hospital - Pharmacy Department Basement West
Miami, Florida, United States
Sylvester Comprehensive Cancer Center-Alex's Place
Miami, Florida, United States
University of Miami / Jackson Memorial Hospital
Miami, Florida, United States
...and 9 more locations
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: Anytime post-dose on Visit 4 (Week 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.
Time frame: 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).
Time frame: 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.
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)