Trial Outcomes & Findings for Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study In Subjects With Osteoarthritic Pain Of The Knee (NCT NCT00689273)

NCT ID: NCT00689273

Last Updated: 2021-07-13

Results Overview

WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with osteoarthritis (OA) of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC pain domain consists of 5 questions scored on 5 point Likert scale (0=minimum pain to 4=maximum pain) where higher score indicates higher pain. It assesses amount of pain experienced due to OA in the study joint in past 48 hours. Total possible pain domain score calculated by addition of scores of each 5 questions ranged from: 0 (minimum) - 20 (maximum), higher scores indicate higher pain.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 159 participants
• Primary outcome timeframe: Baseline, Week 2
• Results posted on: 2021-07-13

Participant Flow

Participant milestones

Measure	PF-04136309 Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Overall Study STARTED	79	78
Overall Study Treated	78	78
Overall Study COMPLETED	66	73
Overall Study NOT COMPLETED	13	5

Reasons for withdrawal

Measure	PF-04136309 Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Overall Study Adverse Event	3	1
Overall Study Lack of Efficacy	3	0
Overall Study Lost to Follow-up	0	2
Overall Study Other	6	2
Overall Study Randomized but not Treated	1	0

Baseline Characteristics

Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study In Subjects With Osteoarthritic Pain Of The Knee

Baseline characteristics by cohort

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.	Total n=156 Participants Total of all reporting groups
Age, Customized Less than 18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized 18 to 44 years	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Age, Customized 45 to 64 years	49 Participants n=5 Participants	60 Participants n=7 Participants	109 Participants n=5 Participants
Age, Customized Greater than or equal to 65 years	26 Participants n=5 Participants	17 Participants n=7 Participants	43 Participants n=5 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	55 Participants n=7 Participants	111 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	23 Participants n=7 Participants	45 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	37 Participants n=5 Participants	37 Participants n=7 Participants	74 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants	31 Participants n=7 Participants	64 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with osteoarthritis (OA) of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC pain domain consists of 5 questions scored on 5 point Likert scale (0=minimum pain to 4=maximum pain) where higher score indicates higher pain. It assesses amount of pain experienced due to OA in the study joint in past 48 hours. Total possible pain domain score calculated by addition of scores of each 5 questions ranged from: 0 (minimum) - 20 (maximum), higher scores indicate higher pain.

Outcome measures

Measure	PF-04136309 n=69 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=74 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Domain Score at Week 2	-3.64 Units on a scale Standard Error 0.41	-3.15 Units on a scale Standard Error 0.40

SECONDARY outcome

Timeframe: Baseline, Week 1

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with OA of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC pain domain consists of 5 questions scored on 5 point Likert scale (0=minimum pain to 4=maximum pain) where higher score indicates higher pain. It assesses amount of pain experienced due to OA in the study joint in past 48 hours. Total possible pain domain score calculated by addition of scores of each 5 questions ranged from: 0 (minimum) - 20 (maximum), higher scores indicate higher pain.

Outcome measures

Measure	PF-04136309 n=76 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=76 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Change From Baseline in WOMAC Pain Domain Score at Week 1	-2.74 Units on a scale Standard Error 0.37	-2.49 Units on a scale Standard Error 0.37

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with OA of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC stiffness domain consist of 2 questions scored on 5 point Likert scale (0=minimum stiffness to 4= maximum stiffness), higher score indicates higher stiffness. It assesses stiffness (sensation of decreased ease) due to OA in study joint in past 48 hours. Total possible stiffness domain score calculated by addition of scores of each 2 questions ranged from: 0 (minimum) to 8 (maximum), higher scores indicate higher stiffness.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Change From Baseline in WOMAC Stiffness Domain Score at Week 1 and Week 2 Week 1	-0.95 Units on a scale Standard Error 0.19	-0.78 Units on a scale Standard Error 0.19
Change From Baseline in WOMAC Stiffness Domain Score at Week 1 and Week 2 Week 2	-1.39 Units on a scale Standard Error 0.20	-1.24 Units on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with OA of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC physical function consists of 17 questions scored on 5 point Likert scale (0=minimum physical impairment to 4=maximum physical impairment), higher score indicates worse function. It assesses worse function (ability to move/perform activity) due to OA in study joint in past 48 hours. Total possible score calculated by addition of scores of each 17 questions ranged from: 0 (minimum) to 68 (maximum), higher scores indicate worse function.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Change From Baseline in WOMAC Physical Function Domain Score at Week 1 and Week 2 Week 1	-8.63 Units on a scale Standard Error 1.26	-7.25 Units on a scale Standard Error 1.29
Change From Baseline in WOMAC Physical Function Domain Score at Week 1 and Week 2 Week 2	-11.32 Units on a scale Standard Error 1.41	-8.90 Units on a scale Standard Error 1.42

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

WOMAC: self-administered, disease-specific instrument assessing clinically important, participant-relevant symptoms for pain, stiffness, physical function in participants with OA of the hip and/or knee. Index consists of 24 questions: 5 (pain), 2 (stiffness), 17 (physical function). Each question was assessed on a 5-point Likert scale (0= none to 4=extreme), higher score indicates worse function. Total WOMAC Score: summation of 24 component item scores, without any correction for relative importance of different subscales. Total score range 0 (minimum) to 96 (maximum), higher score indicate higher symptoms.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Change From Baseline in WOMAC Total Score at Week 1 and Week 2 Week 1	-12.31 Units on a scale Standard Error 1.72	-10.54 Units on a scale Standard Error 1.76
Change From Baseline in WOMAC Total Score at Week 1 and Week 2 Week 2	-16.24 Units on a scale Standard Error 1.96	-13.22 Units on a scale Standard Error 1.98

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

WOMAC: self-administered, disease-specific instrument assessing clinically important, participant-relevant symptoms for pain, stiffness, physical function in participants with OA of hip or knee. Index consists of 24 questions: 5 (pain), 2 (stiffness), 17 (physical function). Each question was assessed on a 5-point Likert scale; score range: 0 (none) to 4 (extreme) where higher score indicates worse function. Importance-weighted total WOMAC score weighs 3 subscales of pain, stiffness, physical function using factors of 0.42, 0.21, and 0.37 to account for relative importance. Total score calculated by applying factors and summing all domains ranged from 0 (minimum) to 35.24 (maximum), higher score indicate higher symptoms.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Change From Baseline in WOMAC Importance Weighted Total Score at Week 1 and Week 2 Week 1	-4.54 Units on a scale Standard Error 0.63	-3.90 Units on a scale Standard Error 0.65
Change From Baseline in WOMAC Importance Weighted Total Score at Week 1 and Week 2 Week 2	-5.97 Units on a scale Standard Error 0.72	-4.84 Units on a scale Standard Error 0.73

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

NRS: participant rated their daily pain on 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Change From Baseline in 11 Point Numeric Pain Rating Scale (NRS) at Week 1 and Week 2 (Weekly Average) Week 1	-0.83 Units on a scale Standard Error 0.14	-0.62 Units on a scale Standard Error 0.14
Change From Baseline in 11 Point Numeric Pain Rating Scale (NRS) at Week 1 and Week 2 (Weekly Average) Week 2	-1.56 Units on a scale Standard Error 0.20	-1.14 Units on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

NRS: participant rated their daily pain on 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 10	-1.49 Units on a scale Standard Error 0.20	-0.84 Units on a scale Standard Error 0.20
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 1	-0.26 Units on a scale Standard Error 0.20	-0.09 Units on a scale Standard Error 0.19
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 2	-0.67 Units on a scale Standard Error 0.20	-0.22 Units on a scale Standard Error 0.20
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 3	-0.81 Units on a scale Standard Error 0.20	-0.46 Units on a scale Standard Error 0.20
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 4	-0.91 Units on a scale Standard Error 0.20	-0.58 Units on a scale Standard Error 0.20
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 5	-1.02 Units on a scale Standard Error 0.20	-0.80 Units on a scale Standard Error 0.20
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 6	-1.11 Units on a scale Standard Error 0.20	-0.97 Units on a scale Standard Error 0.20
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 7	-1.23 Units on a scale Standard Error 0.20	-1.04 Units on a scale Standard Error 0.19
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 8	-1.50 Units on a scale Standard Error 0.20	-1.04 Units on a scale Standard Error 0.20
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 9	-1.35 Units on a scale Standard Error 0.20	-1.03 Units on a scale Standard Error 0.20
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 11	-1.60 Units on a scale Standard Error 0.20	-1.03 Units on a scale Standard Error 0.20
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 12	-1.82 Units on a scale Standard Error 0.20	-1.23 Units on a scale Standard Error 0.20
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 13	-1.76 Units on a scale Standard Error 0.20	-1.43 Units on a scale Standard Error 0.20
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 Day 14	-1.82 Units on a scale Standard Error 0.20	-1.36 Units on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline, Week 2

Population: FAS included all randomized participants who took at least 1 dose of study drug. LOCF method was used to impute missing values.

Participant rated their daily pain on 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain. In this outcome measure number of participants with at least 30% and 50% reduction in average weekly pain score at Week 2 from Baseline are reported. Average weekly score at Week 2 was average of daily pain scores from Day 8 to Day 14 and at Baseline it was average of daily pain scores from Day -6 to Day 0.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Number of Participants With at Least a 30 Percent (%) and 50% Reduction in Average Weekly Pain Score at Week 2: Last Observation Carried Forward (LOCF) 30% Reduction	27 Participants	20 Participants
Number of Participants With at Least a 30 Percent (%) and 50% Reduction in Average Weekly Pain Score at Week 2: Last Observation Carried Forward (LOCF) 50% Reduction	14 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

Participants answered the following question: "Considering all the ways your arthritis affects you, how are you doing today?" Participants rated their condition using the scale assessing the symptoms and limitations to carry out normal daily activities. Score ranged from 1 to 5; where 1= very good (No symptoms and limitations); 2= good (mild symptoms and no limitations); 3= fair (moderate symptoms and some limitations); 4= poor (severe symptoms and inability to carry out most activities); and 5= very Poor (very severe, intolerable symptoms and inability to carry out all activities). Higher scores indicated more limitations in carrying out normal activities.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Change From Baseline in Patient's Global Assessment of Arthritic Condition at Week 1 and Week 2 Week 1	-0.42 Units on a scale Standard Error 0.09	-0.32 Units on a scale Standard Error 0.09
Change From Baseline in Patient's Global Assessment of Arthritic Condition at Week 1 and Week 2 Week 2	-0.56 Units on a scale Standard Error 0.09	-0.44 Units on a scale Standard Error 0.09

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to 30 days after last dose of study drug (up to Day 44)

Population: FAS included all randomized participants who took at least 1 dose of study drug.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. SAE was defined as any untoward medical occurrence at any dose that: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Treatment emergent AEs included both SAEs and all non-SAEs.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Treatment Emergent AEs	22 Participants	21 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Treatment Emergent SAEs	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to 30 days after last dose of study drug (up to Day 44)

Population: FAS included all randomized participants who took at least 1 dose of study drug.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Treatment emergent AEs included both SAEs and all non-SAEs. A treatment-related SAE was a treatment-related AE and was defined as any untoward medical occurrence at any dose that: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. Relatedness to study drug was assessed by the investigator.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Number of Participants With Treatment Emergent Treatment Related AEs and SAEs Treatment Emergent Treatment Related AEs	13 Participants	16 Participants
Number of Participants With Treatment Emergent Treatment Related AEs and SAEs Treatment Emergent Treatment Related SAEs	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to 30 days after last dose of study drug (up to Day 44)

Population: FAS included all randomized participants who took at least 1 dose of study drug.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Number of Participants Who Discontinued Due to Treatment Emergent AEs and Treatment Emergent Treatment Related AEs Treatment Emergent AEs	3 Participants	1 Participants
Number of Participants Who Discontinued Due to Treatment Emergent AEs and Treatment Emergent Treatment Related AEs Treatment Emergent Treatment Related AEs	1 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to 30 days after last dose of study drug (up to Day 44)

Population: FAS included all randomized participants who took at least 1 dose of study drug.

Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. The severity grades (mild, moderate and severe) were defined as - Mild: did not interfere with participant's usual function, Moderate: Interfered to some extent with participant's usual function and Severe: Interfered significantly with participant's usual function.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Number of Treatment-Emergent AEs by Severity Mild	24 Events	29 Events
Number of Treatment-Emergent AEs by Severity Moderate	2 Events	9 Events
Number of Treatment-Emergent AEs by Severity Severe	2 Events	1 Events

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to 30 days after last dose of study drug (up to Day 44)

Population: FAS included all randomized participants who took at least 1 dose of study drug.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. The severity grades (mild, moderate and severe) were defined as - Mild: did not interfere with participant's usual function, Moderate: Interfered to some extent with participant's usual function and Severe: Interfered significantly with participant's usual function.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Number of Treatment-Emergent Treatment-Related AEs by Severity Mild	13 Events	18 Events
Number of Treatment-Emergent Treatment-Related AEs by Severity Moderate	1 Events	4 Events
Number of Treatment-Emergent Treatment-Related AEs by Severity Severe	1 Events	1 Events

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to 30 days after last dose of study drug (up to Day 44)

Population: FAS included all randomized participants who took at least 1 dose of study drug.

Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. The severity grades (mild, moderate and severe) were defined as - Mild: did not interfere with participant's usual function, Moderate: Interfered to some extent with participant's usual function and Severe: Interfered significantly with participant's usual function.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity Mild	1 Participants	1 Participants
Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity Moderate	1 Participants	0 Participants
Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity Severe	1 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to Week 2

Population: FAS included all randomized participants who took at least 1 dose of study drug.

Criteria for clinical significance: sitting, standing or supine pulse rate <40 beats per minute (bpm) or >120 bpm; sitting, standing or supine diastolic blood pressure < 50 millimeter of mercury (mmHg); sitting, standing or supine systolic blood pressure < 90 mmHg. Clinical significance was judged by the investigator.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Number of Participants With Clinically Significant Change From Baseline in Blood Pressure and Pulse Rate	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 2

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified rows.

Change (increase) from baseline of greater than or equal to (>=) 25% in maximum PR Interval and maximum QRS complex in milliseconds (msec). Change (increase) from baseline of >= 30 msec and less than (<) 60 msec or change >= 60 msec in maximum QTc and maximum QT interval with Fridericia's Correction (QTcF).

Outcome measures

Measure	PF-04136309 n=77 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=77 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters Maximum PR Interval increase from baseline; change >=25%	0 Participants	0 Participants
Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters Maximum QRS Complex increase from baseline; change >=25%	0 Participants	0 Participants
Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters Maximum QTc Interval increase from baseline; Change >=30 msec and < 60 msec	1 Participants	0 Participants
Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters Maximum QTc Interval increase from baseline; Change >=60 msec	1 Participants	0 Participants
Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters Maximum QTcF Interval increase from baseline; Change >=30 msec and < 60 msec	1 Participants	0 Participants
Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters Maximum QTcF Interval increase from baseline; Change >=60 msec	1 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 and Day 14: Pre-dose and 6,7 hours post-dose

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

In this outcome measure data for reporting arm PF-04136309 was collected and reported as planned.

Outcome measures

Measure	PF-04136309 n=78 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Plasma Concentration Versus Time of PF-04136309 Day 1: pre-dose	257.90 Nanogram per milliliter Standard Deviation 276.38	—
Plasma Concentration Versus Time of PF-04136309 Day 1: 6 hours post-dose	587.54 Nanogram per milliliter Standard Deviation 626.53	—
Plasma Concentration Versus Time of PF-04136309 Day 1: 7 hours post-dose	590.85 Nanogram per milliliter Standard Deviation 615.06	—
Plasma Concentration Versus Time of PF-04136309 Day 14: 0 hours pre-dose	227.42 Nanogram per milliliter Standard Deviation 259.21	—
Plasma Concentration Versus Time of PF-04136309 Day 14: 6 hours post-dose	388.00 Nanogram per milliliter Standard Deviation 244.98	—
Plasma Concentration Versus Time of PF-04136309 Day 14: 7 hours post-dose	426.14 Nanogram per milliliter Standard Deviation 266.11	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 14

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Outcome measures

Measure	PF-04136309 n=77 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=77 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Change From Baseline in Absolute Monocyte Count at Day 14	-0.13 Thousand cells per millimeter cube Interval -0.19 to -0.04	-0.01 Thousand cells per millimeter cube Interval -0.06 to 0.06

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 14

Population: FAS included all randomized participants who took at least 1 dose of study drug. Here 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Monocytes (percent) were derived as monocyte absolute counts per white blood cell absolute counts*100.

Outcome measures

Measure	PF-04136309 n=77 Participants Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=77 Participants Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Change From Baseline in Percent Monocytes at Day 14	-1.7 Percent monocytes Interval -2.7 to -0.1	0.0 Percent monocytes Interval -0.8 to 1.0

Adverse Events

PF-04136309

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	PF-04136309 n=78 participants at risk Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Placebo n=78 participants at risk Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Cardiac disorders Atrial fibrillation	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Sinus tachycardia	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Eye disorders Eye pain	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Eye disorders Vision blurred	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	2.6% 2/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	5.1% 4/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dry mouth	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	2.6% 2/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	3.8% 3/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
General disorders Chest pain	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
General disorders Fatigue	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	2.6% 2/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
General disorders Oedema peripheral	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	2.6% 2/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
General disorders Pain	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
General disorders Ulcer	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Influenza	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Contusion	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fall	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Joint injury	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Periorbital haematoma	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Investigations Blood creatinine increased	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	2.6% 2/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Investigations Blood glucose increased	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Investigations Creatinine renal clearance decreased	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Investigations Electrocardiogram QT prolonged	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Investigations Electrocardiogram T wave amplitude decreased	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Investigations Hepatic enzyme increased	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypercalcaemia	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	2.6% 2/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	2.6% 2/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	2.6% 2/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Headache	7.7% 6/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	3.8% 3/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Somnolence	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	2.6% 2/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Acne	2.6% 2/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Flushing	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	0.00% 0/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.	1.3% 1/78 • From Baseline up to 30 days after last dose of study drug (up to Day 44) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.

Additional Information

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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.
• Publication restrictions are in place

Restriction type: OTHER