Moderate-severe Pain
Conditions
Keywords
Pediatric, pain indication, controlled release morphine
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.
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.
Interventions
DRUGAges 7-11
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.
DRUGages 12-17
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.
Sponsors
Pfizer
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 | 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. |
| Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 of Week 5 | 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 | 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 | 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 | 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 | 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 | 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). |
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 1 to Week 4 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Laboratory Test Abnormalities | Week 1 up to Week 10 | 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). |
| Apparent Volume of Distribution (Vz/F) of PF-06412528 | Anytime post-dose on Visit 4 (Week 4) | 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. |
| Dose-Exposure Relationship of Metabolites of Morphine, Naltrexone and 6-β-Naltrexol | Anytime post-dose on Visit 4 (Week 4) | — |
| Number of Participants With Pre-defined Criteria of Vital Signs | Week 1 up to Week 10 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-06412528 <=20 mg Participants were converted from their pre-study standard of care opioid analgesic to PF-06412528; PF-06412528 oral dose was titrated and stabilized to less than or equal to (\<=) 20 milligram (mg) daily, up to a maximum of 4 weeks. Participants continued to receive stabilized PF-06412528 \<=20 mg oral daily dose up to a maximum of additional 6 weeks. | 6 |
| PF-06412528 >20-40 mg Participants were converted from their pre-study standard of care opioid analgesic to PF-06412528; PF-06412528 oral dose was titrated and stabilized to greater than (\>) 20 mg to 40 mg daily, up to a maximum of 4 weeks. Participants continued to receive stabilized PF-06412528 \>20 mg to 40 mg oral daily dose up to a maximum of additional 6 weeks. | 10 |
| PF-06412528 >40-80 mg Participants were converted from their pre-study standard of care opioid analgesic to PF-06412528; PF-06412528 oral dose was titrated and stabilized to \>40 mg to 80 mg daily, up to a maximum of 4 weeks. Participants continued to receive stabilized PF-06412528 \>40 mg to 80 mg oral daily dose up to a maximum of additional 6 weeks. | 3 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 1 |
| Overall Study | Insufficient Clinical Response | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Withdrawl by Parents/Guardians | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | PF-06412528 <=20 mg | PF-06412528 >20-40 mg | PF-06412528 >40-80 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 14.3 years STANDARD_DEVIATION 2.34 | 15.0 years STANDARD_DEVIATION 1.33 | 15.3 years STANDARD_DEVIATION 1.53 | 14.8 years STANDARD_DEVIATION 1.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 4 Participants | 0 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 6 Participants | 3 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 7 Participants | 1 Participants | 11 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 0 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 10 | 0 / 3 |
| other Total, other adverse events | 5 / 6 | 9 / 10 | 3 / 3 |
| serious Total, serious adverse events | 2 / 6 | 2 / 10 | 2 / 3 |
Outcome results
Primary
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)
Population: Data for this outcome measure was not collected, as there were insufficient pharmacokinetic samples due to early termination of the study by the sponsor.
Primary
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)
Population: Data for this outcome measure was not collected, as there were insufficient pharmacokinetic samples due to early termination of the study by the sponsor.
Primary
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)
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 1 to Week 4.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 | COWS Score < 5 | 6 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 | Mild (COWS Score 5-12) | 0 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 | COWS Score < 5 | 9 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 | Mild (COWS Score 5-12) | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 | Mild (COWS Score 5-12) | 0 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 | COWS Score < 5 | 3 Participants |
Primary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 5 to Week 10.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 of Week 5 | COWS Score <5 | 4 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 of Week 5 | Mild (COWS Score 5-12) | 0 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 of Week 5 | COWS Score <5 | 7 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 of Week 5 | Mild (COWS Score 5-12) | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 of Week 5 | COWS Score <5 | 2 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 of Week 5 | Mild (COWS Score 5-12) | 0 Participants |
Primary
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)
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 5 to Week 10.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 | Mild (COWS Score 5-12) | 0 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 | COWS Score <5 | 3 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 | Missing | 1 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 | Mild (COWS Score 5-12) | 1 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 | COWS Score <5 | 6 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 | Missing | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 | COWS Score <5 | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 | Missing | 0 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 | Mild (COWS Score 5-12) | 1 Participants |
Primary
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)
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 1 to Week 4.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 4 | COWS Score <5 | 2 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 4 | Missing | 4 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 4 | COWS Score <5 | 2 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 4 | Missing | 8 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 4 | COWS Score <5 | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 4 | Missing | 2 Participants |
Primary
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)
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 1 to Week 4.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening Before Day 1 | COWS Score < 5 | 6 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening Before Day 1 | Mild (COWS Score 5-12) | 0 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening Before Day 1 | COWS Score < 5 | 9 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening Before Day 1 | Mild (COWS Score 5-12) | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening Before Day 1 | COWS Score < 5 | 3 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening Before Day 1 | Mild (COWS Score 5-12) | 0 Participants |
Primary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 5 to Week 10.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening on Week 5 | 4 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening on Week 5 | 8 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening on Week 5 | 2 Participants |
Primary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 1 to Week 4.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1 | Missing | 0 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1 | COWS Score < 5 | 6 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1 | Mild (COWS Score 5-12) | 0 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1 | COWS Score < 5 | 8 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1 | Mild (COWS Score 5-12) | 1 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1 | Missing | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1 | COWS Score < 5 | 3 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1 | Mild (COWS Score 5-12) | 0 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1 | Missing | 0 Participants |
Primary
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
Population: Analysis population: all participants who were screened and received at least 1 dose of PF-06412528 from Week 5-10. Overall number of participants analyzed=0 for arm PF-06412528 \>40-80 mg as no participants were evaluable for this outcome measure at Week 10.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 10 | COWS Score <5 | 1 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 10 | Missing | 7 Participants |
Primary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 1 to Week 4. Overall number of participants analyzed=0 for arm PF-06412528 \>40-80 mg as no participants were evaluable for this outcome measure at Week 2.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 2 | COWS Score < 5 | 1 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 2 | Missing | 5 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 2 | COWS Score < 5 | 9 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 2 | Missing | 1 Participants |
Primary
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
Population: Analysis population: all participants who were screened and had received at least 1 dose of PF-06412528 from Week 1-4. Overall number of participants analyzed=0 for arm PF-06412528 \>40-80 mg as no participants were evaluable for this outcome measure at Week 3.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 3 | COWS Score <5 | 1 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 3 | Missing | 5 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 3 | Missing | 7 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 3 | COWS Score <5 | 3 Participants |
Primary
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
Population: Analysis population: all participants who were screened and received at least 1 dose of PF-06412528 from Week 1-4. Overall number of participants analyzed=0 for arm PF-06412528 \<=20 mg and PF-06412528 \>40-80 mg as no participants were evaluable for this outcome measure at Week 4.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 4 | COWS Score <5 | 2 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 4 | Missing | 8 Participants |
Primary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 5 to Week 10.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 6 | COWS Score <5 | 4 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 6 | Mild (COWS Score 5-12) | 0 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 6 | COWS Score <5 | 7 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 6 | Mild (COWS Score 5-12) | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 6 | COWS Score <5 | 2 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 6 | Mild (COWS Score 5-12) | 0 Participants |
Primary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 5 to Week 10.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8 | Mild (COWS Score 5-12) | 0 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8 | COWS Score <5 | 3 Participants |
| PF-06412528 <=20 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8 | Missing | 1 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8 | Mild (COWS Score 5-12) | 0 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8 | COWS Score <5 | 7 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8 | Missing | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8 | COWS Score <5 | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8 | Missing | 0 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8 | Mild (COWS Score 5-12) | 1 Participants |
Primary
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.
Time frame: Week 1 to Week 4
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 1 to Week 4.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4 | Moderate | 0 Participants |
| PF-06412528 <=20 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4 | Mild | 1 Participants |
| PF-06412528 <=20 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4 | Severe | 3 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4 | Moderate | 3 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4 | Mild | 4 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4 | Severe | 2 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4 | Mild | 2 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4 | Severe | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4 | Moderate | 0 Participants |
Primary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 5 to Week 10.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10 | Moderate | 1 Participants |
| PF-06412528 <=20 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10 | Mild | 1 Participants |
| PF-06412528 <=20 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10 | Severe | 1 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10 | Moderate | 2 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10 | Mild | 3 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10 | Severe | 2 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10 | Mild | 0 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10 | Severe | 2 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10 | Moderate | 0 Participants |
Primary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 1 to Week 4.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 1 to Week 4 | AEs | 4 Participants |
| PF-06412528 <=20 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 1 to Week 4 | SAEs | 1 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 1 to Week 4 | AEs | 9 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 1 to Week 4 | SAEs | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 1 to Week 4 | AEs | 3 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 1 to Week 4 | SAEs | 1 Participants |
Primary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 5 to Week 10.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 5 to Week 10 | AEs | 3 Participants |
| PF-06412528 <=20 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 5 to Week 10 | SAEs | 1 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 5 to Week 10 | AEs | 7 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 5 to Week 10 | SAEs | 2 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 5 to Week 10 | AEs | 2 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 5 to Week 10 | SAEs | 1 Participants |
Primary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 1 to Week 4.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Treatment Emergent Treatment Related Adverse Events: Week 1 to Week 4 | 2 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Treatment Emergent Treatment Related Adverse Events: Week 1 to Week 4 | 4 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Treatment Emergent Treatment Related Adverse Events: Week 1 to Week 4 | 0 Participants |
Primary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 from Week 5 to Week 10.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Treatment Emergent Treatment Related Adverse Events: Week 5 to Week 10 | 2 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Treatment Emergent Treatment Related Adverse Events: Week 5 to Week 10 | 4 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Treatment Emergent Treatment Related Adverse Events: Week 5 to Week 10 | 1 Participants |
Secondary
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)
Population: Data for this outcome measure was not collected, as there were insufficient pharmacokinetic samples due to early termination of the study by the sponsor.
Secondary
Dose-Exposure Relationship of Metabolites of Morphine, Naltrexone and 6-β-Naltrexol
Time frame: Anytime post-dose on Visit 4 (Week 4)
Population: Data for this outcome measure was not collected, as there were insufficient pharmacokinetic samples due to early termination of the study by the sponsor.
Secondary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 in the study and evaluated for laboratory abnormalities.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Laboratory Test Abnormalities | 7 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Laboratory Test Abnormalities | 3 Participants |
Secondary
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
Population: Analysis population included all participants who were screened and had received at least 1 dose of PF-06412528 in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06412528 <=20 mg | Number of Participants With Pre-defined Criteria of Vital Signs | Supine DBP: Change >= 20 mmHg increase | 0 Participants |
| PF-06412528 <=20 mg | Number of Participants With Pre-defined Criteria of Vital Signs | Supine DBP: Change >= 20 mmHg decrease | 1 Participants |
| PF-06412528 <=20 mg | Number of Participants With Pre-defined Criteria of Vital Signs | Supine SBP: Change >= 30mmHg increase | 1 Participants |
| PF-06412528 <=20 mg | Number of Participants With Pre-defined Criteria of Vital Signs | Supine SBP: Change >= 30 mmHg decrease | 0 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Pre-defined Criteria of Vital Signs | Supine SBP: Change >= 30 mmHg decrease | 0 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Pre-defined Criteria of Vital Signs | Supine DBP: Change >= 20 mmHg increase | 2 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Pre-defined Criteria of Vital Signs | Supine SBP: Change >= 30mmHg increase | 0 Participants |
| PF-06412528 >20-40 mg | Number of Participants With Pre-defined Criteria of Vital Signs | Supine DBP: Change >= 20 mmHg decrease | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Pre-defined Criteria of Vital Signs | Supine SBP: Change >= 30 mmHg decrease | 0 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Pre-defined Criteria of Vital Signs | Supine DBP: Change >= 20 mmHg decrease | 1 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Pre-defined Criteria of Vital Signs | Supine SBP: Change >= 30mmHg increase | 0 Participants |
| PF-06412528 >40-80 mg | Number of Participants With Pre-defined Criteria of Vital Signs | Supine DBP: Change >= 20 mmHg increase | 0 Participants |