Trial Outcomes & Findings for Safety and Pharmacokinetic Study of EMBEDA in Children Ages 7-17 With Pain (NCT NCT02101554)

Last Updated: 2020-07-10

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

19 participants

Primary outcome timeframe

Week 1 to Week 4

Results posted on

2020-07-10

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	6	10	3
Overall Study COMPLETED	3	5	2
Overall Study NOT COMPLETED	3	5	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Overall Study Protocol Violation	0	1	0
Overall Study Insufficient Clinical Response	0	2	0
Overall Study Adverse Event	2	1	1
Overall Study Lost to Follow-up	0	1	0
Overall Study Withdrawl by Parents/Guardians	1	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PF-06412528 <=20 mg n=6 Participants 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.	PF-06412528 >20-40 mg n=10 Participants 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.	PF-06412528 >40-80 mg n=3 Participants 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.	Total n=19 Participants Total of all reporting groups
Age, Continuous	14.3 years STANDARD_DEVIATION 2.34 • n=99 Participants	15.0 years STANDARD_DEVIATION 1.33 • n=107 Participants	15.3 years STANDARD_DEVIATION 1.53 • n=206 Participants	14.8 years STANDARD_DEVIATION 1.68 • n=7 Participants
Sex: Female, Male Female	3 Participants n=99 Participants	7 Participants n=107 Participants	3 Participants n=206 Participants	13 Participants n=7 Participants
Sex: Female, Male Male	3 Participants n=99 Participants	3 Participants n=107 Participants	0 Participants n=206 Participants	6 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=99 Participants	4 Participants n=107 Participants	0 Participants n=206 Participants	8 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=99 Participants	6 Participants n=107 Participants	3 Participants n=206 Participants	11 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	2 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants	6 Participants n=7 Participants
Race (NIH/OMB) White	3 Participants n=99 Participants	7 Participants n=107 Participants	1 Participants n=206 Participants	11 Participants n=7 Participants
Race (NIH/OMB) More than one race	1 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=6 Participants 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.	PF-06412528 >20-40 mg n=10 Participants 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.	PF-06412528 >40-80 mg n=3 Participants 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.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 1 to Week 4 AEs	4 Participants	9 Participants	3 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 1 to Week 4 SAEs	1 Participants	1 Participants	1 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=4 Participants 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.	PF-06412528 >20-40 mg n=8 Participants 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.	PF-06412528 >40-80 mg n=2 Participants 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.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 5 to Week 10 AEs	3 Participants	7 Participants	2 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Week 5 to Week 10 SAEs	1 Participants	2 Participants	1 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=6 Participants 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.	PF-06412528 >20-40 mg n=10 Participants 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.	PF-06412528 >40-80 mg n=3 Participants 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.
Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4 Mild	1 Participants	4 Participants	2 Participants
Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4 Moderate	0 Participants	3 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 1 to Week 4 Severe	3 Participants	2 Participants	1 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=4 Participants 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.	PF-06412528 >20-40 mg n=8 Participants 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.	PF-06412528 >40-80 mg n=2 Participants 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.
Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10 Mild	1 Participants	3 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10 Moderate	1 Participants	2 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events According to Severity: Week 5 to Week 10 Severe	1 Participants	2 Participants	2 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=6 Participants 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.	PF-06412528 >20-40 mg n=10 Participants 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.	PF-06412528 >40-80 mg n=3 Participants 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.
Number of Participants With Treatment Emergent Treatment Related Adverse Events: Week 1 to Week 4	2 Participants	4 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=4 Participants 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.	PF-06412528 >20-40 mg n=8 Participants 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.	PF-06412528 >40-80 mg n=2 Participants 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.
Number of Participants With Treatment Emergent Treatment Related Adverse Events: Week 5 to Week 10	2 Participants	4 Participants	1 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=6 Participants 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.	PF-06412528 >20-40 mg n=10 Participants 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.	PF-06412528 >40-80 mg n=3 Participants 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening Before Day 1 COWS Score < 5	6 Participants	9 Participants	3 Participants
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening Before Day 1 Mild (COWS Score 5-12)	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=6 Participants 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.	PF-06412528 >20-40 mg n=10 Participants 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.	PF-06412528 >40-80 mg n=3 Participants 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 COWS Score < 5	6 Participants	9 Participants	3 Participants
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 Mild (COWS Score 5-12)	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=6 Participants 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.	PF-06412528 >20-40 mg n=10 Participants 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.	PF-06412528 >40-80 mg n=3 Participants 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1 COWS Score < 5	6 Participants	8 Participants	3 Participants
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1 Mild (COWS Score 5-12)	0 Participants	1 Participants	0 Participants
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 1 Missing	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=6 Participants 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.	PF-06412528 >20-40 mg n=10 Participants 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.	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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 2 COWS Score < 5	1 Participants	9 Participants	—
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 2 Missing	5 Participants	1 Participants	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=6 Participants 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.	PF-06412528 >20-40 mg n=10 Participants 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.	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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 3 COWS Score <5	1 Participants	3 Participants	—
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 3 Missing	5 Participants	7 Participants	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	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.	PF-06412528 >20-40 mg n=10 Participants 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.	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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 4 COWS Score <5	—	2 Participants	—
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 4 Missing	—	8 Participants	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=6 Participants 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.	PF-06412528 >20-40 mg n=10 Participants 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.	PF-06412528 >40-80 mg n=3 Participants 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 4 COWS Score <5	2 Participants	2 Participants	1 Participants
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 4 Missing	4 Participants	8 Participants	2 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=4 Participants 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.	PF-06412528 >20-40 mg n=8 Participants 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.	PF-06412528 >40-80 mg n=2 Participants 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Screening on Week 5	4 Participants	8 Participants	2 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=4 Participants 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.	PF-06412528 >20-40 mg n=8 Participants 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.	PF-06412528 >40-80 mg n=2 Participants 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 of Week 5 COWS Score <5	4 Participants	7 Participants	2 Participants
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Day 1 of Week 5 Mild (COWS Score 5-12)	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=4 Participants 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.	PF-06412528 >20-40 mg n=8 Participants 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.	PF-06412528 >40-80 mg n=2 Participants 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 6 COWS Score <5	4 Participants	7 Participants	2 Participants
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 6 Mild (COWS Score 5-12)	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=4 Participants 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.	PF-06412528 >20-40 mg n=8 Participants 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.	PF-06412528 >40-80 mg n=2 Participants 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8 COWS Score <5	3 Participants	7 Participants	1 Participants
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8 Mild (COWS Score 5-12)	0 Participants	0 Participants	1 Participants
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 8 Missing	1 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	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.	PF-06412528 >20-40 mg n=8 Participants 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.	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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 10 COWS Score <5	—	1 Participants	—
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Week 10 Missing	—	7 Participants	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=4 Participants 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.	PF-06412528 >20-40 mg n=8 Participants 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.	PF-06412528 >40-80 mg n=2 Participants 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.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 COWS Score <5	3 Participants	6 Participants	1 Participants
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 Mild (COWS Score 5-12)	0 Participants	1 Participants	1 Participants
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) at Early Termination Before Week 10 Missing	1 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=6 Participants 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.	PF-06412528 >20-40 mg n=10 Participants 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.	PF-06412528 >40-80 mg n=3 Participants 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.
Number of Participants With Pre-defined Criteria of Vital Signs Supine DBP: Change >= 20 mmHg increase	0 Participants	2 Participants	0 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Supine DBP: Change >= 20 mmHg decrease	1 Participants	1 Participants	1 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Supine SBP: Change >= 30mmHg increase	1 Participants	0 Participants	0 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Supine SBP: Change >= 30 mmHg decrease	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	PF-06412528 <=20 mg n=6 Participants 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.	PF-06412528 >20-40 mg n=8 Participants 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.	PF-06412528 >40-80 mg n=3 Participants 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.
Number of Participants With Laboratory Test Abnormalities	3 Participants	7 Participants	3 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

PF-06412528 <=20 mg

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

PF-06412528 >20-40 mg

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

PF-06412528 >40-80 mg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PF-06412528 <=20 mg n=6 participants at risk 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.	PF-06412528 >20-40 mg n=10 participants at risk 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.	PF-06412528 >40-80 mg n=3 participants at risk 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.
Blood and lymphatic system disorders Sickle cell anaemia with crisis	0.00% 0/6 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	10.0% 1/10 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	33.3% 1/3 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	0.00% 0/10 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	0.00% 0/3 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.
General disorders Pyrexia	0.00% 0/6 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	0.00% 0/10 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	33.3% 1/3 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.
Hepatobiliary disorders Cholecystitis acute	16.7% 1/6 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	0.00% 0/10 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	0.00% 0/3 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.
Infections and infestations Osteomyelitis	0.00% 0/6 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	10.0% 1/10 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	0.00% 0/3 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.
Infections and infestations Pneumonia	0.00% 0/6 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	0.00% 0/10 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	33.3% 1/3 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.
Musculoskeletal and connective tissue disorders Bone infarction	0.00% 0/6 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	0.00% 0/10 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	33.3% 1/3 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/6 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	0.00% 0/10 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.	33.3% 1/3 • Week 1 up to Week 11 (including 1 week of follow-up) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The study was terminated early therefore the number of participants is small and safety data (all-cause mortality, SAE and other AEs) are presented by dose group.

Other adverse events

Additional Information

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Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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Restriction type: OTHER