Osteoarthritis, Knee
Conditions
Keywords
PF-04136309 CCR2 osteoarthritic pain knee, phase 2 placebo multicenter double-blind placebo-controlled
Brief summary
To evaluate the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics in patients with osteoarthritic pain of the knee. The most painful knee joint will be identified as the index joint at screening, and this joint will be used for all pain assessments throughout the study.
Interventions
DRUGPF-04136309
125 mg capsules. Dose will be 4 capsules BID for 2 weeks for a total of 500 mg for each dosing interval.
DRUGPlacebo
Placebo will be matched to PF-04136309. Dose, frequency, and duration same as PF-04136309.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female of any race, between the ages of 18 and 75 years inclusive * Female subjects must be of non-childbearing potential and have a negative pregnancy test at Screening. * Osteoarthritis of the knee of at least 6 months duration and meeting the American College of Rheumatology Criteria. For radiographic criteria the Xray must have been taken within the last 5 years. If none is available, one should be taken and the diagnostic criteria confirmed prior to randomization. * Willing and able to discontinue all current analgesic therapy, including OTC pain medications and topical analgesics for OA pain, for period beginning with washout phase (lasting 2 days or 5 half-lives of patient's current analgesic medication prior to Day -6) and continuing for the entire duration of study. As an exception, acetaminophen may be used for non-joint related pain at doses ≤1 g/day at the discretion of a qualified member of the study team. * If a subject has evidence or a history of clinically significant endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, renal, psychiatric, or neurological disease, the investigator must confirm that the disease is stable (at least 4 weeks) and under control. * QTc interval ≤450 msec and a PR interval ≤210 msec on Screening ECG.
Exclusion criteria
* Pregnant or lactating females, and females of childbearing potential. * Arthroscopy performed on index knee within 1 year of screening. * Active depression as defined by or meeting The Hospital Anxiety and Depression Scale (HADS) of \>10. * Unwillingness to refrain from consumption of grapefruit or grapefruit juice from 7 days prior to the first dose of study medication until completion of the study. * First degree or higher AV block, defined as PR interval \>210 msecs, bundle branch block, fascicular block or intraventricular conduction delay or clinically relevant abnormality on screening ECG. * Active malignancy of any type or history of a malignancy within 10 years (with the exception of subjects with a history of treated basal cell carcinoma). * Symptomatic OA of the hip ipsilateral to index knee which the patient considers more painful than the knee. * Use of prohibited medications as listed below, in the absence of appropriate washout period. The following analgesic agents must be discontinued within 48 hours or 5 half lives of the analgesic being washed out prior to the baseline period (Day -6 to Day 0); * NSAIDs and selective COX-2 inhibitors; * Acetaminophen ( as an exception acetaminophen may be used for non-joint related pain at doses ≤1g/day); * Opioids. * Oral or I/M corticosteroids within 4 weeks prior to screening. I/A steroids within 12 weeks prior to baseline in study joint or any other joints within 4 weeks prior to baseline, or I/A hyaluronic acid within 24 weeks prior to baseline; * Use of concomitant medications that are CYP3A inhibitors or CYP3A inducers, or that are P-glycoprotein substrates within 48 hours or 5 half lives prior to baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Domain Score at Week 2 | Baseline, Week 2 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in WOMAC Stiffness Domain Score at Week 1 and Week 2 | Baseline, Weeks 1, 2 | 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. |
| Change From Baseline in WOMAC Physical Function Domain Score at Week 1 and Week 2 | Baseline, Weeks 1, 2 | 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. |
| Change From Baseline in WOMAC Total Score at Week 1 and Week 2 | Baseline, Weeks 1, 2 | 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. |
| Change From Baseline in WOMAC Importance Weighted Total Score at Week 1 and Week 2 | Baseline, Weeks 1, 2 | 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. |
| Change From Baseline in WOMAC Pain Domain Score at Week 1 | Baseline, Week 1 | 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. |
| Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Baseline, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 | 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. |
| 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) | Baseline, Week 2 | 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. |
| Change From Baseline in Patient's Global Assessment of Arthritic Condition at Week 1 and Week 2 | Baseline, Weeks 1, 2 | 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. |
| Change From Baseline in 11 Point Numeric Pain Rating Scale (NRS) at Week 1 and Week 2 (Weekly Average) | Baseline, Weeks 1, 2 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Baseline up to 30 days after last dose of study drug (up to Day 44) | 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. |
| Change From Baseline in Percent Monocytes at Day 14 | Baseline, Day 14 | Monocytes (percent) were derived as monocyte absolute counts per white blood cell absolute counts\*100. |
| Number of Participants With Treatment Emergent Treatment Related AEs and SAEs | From Baseline up to 30 days after last dose of study drug (up to Day 44) | 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. |
| Number of Participants Who Discontinued Due to Treatment Emergent AEs and Treatment Emergent Treatment Related AEs | From Baseline up to 30 days after last dose of study drug (up to Day 44) | 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. |
| Number of Treatment-Emergent AEs by Severity | From Baseline up to 30 days after last dose of study drug (up to Day 44) | 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. |
| Number of Treatment-Emergent Treatment-Related AEs by Severity | From Baseline up to 30 days after last dose of study drug (up to Day 44) | 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. |
| Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity | From Baseline up to 30 days after last dose of study drug (up to Day 44) | 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. |
| Number of Participants With Clinically Significant Change From Baseline in Blood Pressure and Pulse Rate | From Baseline up to Week 2 | 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. |
| Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters | Baseline up to Week 2 | 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). |
| Plasma Concentration Versus Time of PF-04136309 | Day 1 and Day 14: Pre-dose and 6,7 hours post-dose | In this outcome measure data for reporting arm PF-04136309 was collected and reported as planned. |
| Change From Baseline in Absolute Monocyte Count at Day 14 | Baseline, Day 14 | — |
Countries
South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 78 |
| 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. | 78 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 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
| Characteristic | PF-04136309 | Placebo | Total |
|---|---|---|---|
| Age, Customized 18 to 44 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Customized 45 to 64 years | 49 Participants | 60 Participants | 109 Participants |
| Age, Customized Greater than or equal to 65 years | 26 Participants | 17 Participants | 43 Participants |
| Age, Customized Less than 18 years | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 37 Participants | 37 Participants | 74 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 7 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) White | 33 Participants | 31 Participants | 64 Participants |
| Sex: Female, Male Female | 56 Participants | 55 Participants | 111 Participants |
| Sex: Female, Male Male | 22 Participants | 23 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 78 | 0 / 78 |
| other Total, other adverse events | 22 / 78 | 21 / 78 |
| serious Total, serious adverse events | 0 / 78 | 0 / 78 |
Outcome results
Primary
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Domain Score at Week 2
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PF-04136309 | 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 |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Domain Score at Week 2 | -3.15 Units on a scale | Standard Error 0.4 |
Comparison: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect. One-sided alpha of 0.1 was used for the analysis.p-value: 0.3980% CI: [-1.23, 0.24]Mixed Models Analysis
Secondary
Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| PF-04136309 | 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 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 11 | -1.03 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 1 | -0.09 Units on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 8 | -1.04 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 2 | -0.22 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 14 | -1.36 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 3 | -0.46 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 9 | -1.03 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 4 | -0.58 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 12 | -1.23 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 5 | -0.80 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 10 | -0.84 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 6 | -0.97 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 13 | -1.43 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 | Day 7 | -1.04 Units on a scale | Standard Error 0.19 |
Comparison: Day 1: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.5580% CI: [-0.52, 0.19]Mixed Models Analysis
Comparison: Day 2: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.1180% CI: [-0.81, -0.09]Mixed Models Analysis
Comparison: Day 3: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.280% CI: [-0.71, 0]Mixed Models Analysis
Comparison: Day 4: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.2380% CI: [-0.69, 0.02]Mixed Models Analysis
Comparison: Day 5: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.4180% CI: [-0.58, 0.13]Mixed Models Analysis
Comparison: Day 6: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.6280% CI: [-0.49, 0.22]Mixed Models Analysis
Comparison: Day 7: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.4980% CI: [-0.55, 0.16]Mixed Models Analysis
Comparison: Day 8: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.180% CI: [-0.81, -0.1]Mixed Models Analysis
Comparison: Day 9: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.2480% CI: [-0.69, 0.03]Mixed Models Analysis
Comparison: Day 10: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.0280% CI: [-1.01, -0.28]Mixed Models Analysis
Comparison: Day 11: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.0480% CI: [-0.93, -0.21]Mixed Models Analysis
Comparison: Day 12: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.0480% CI: [-0.95, -0.23]Mixed Models Analysis
Comparison: Day 13: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.2480% CI: [-0.7, 0.03]Mixed Models Analysis
Comparison: Day 14: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.1180% CI: [-0.82, -0.09]Mixed Models Analysis
Secondary
Change From Baseline in 11 Point Numeric Pain Rating Scale (NRS) at Week 1 and Week 2 (Weekly Average)
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04136309 | 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 |
| PF-04136309 | 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 0.2 |
| Placebo | Change From Baseline in 11 Point Numeric Pain Rating Scale (NRS) at Week 1 and Week 2 (Weekly Average) | Week 1 | -0.62 Units on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline in 11 Point Numeric Pain Rating Scale (NRS) at Week 1 and Week 2 (Weekly Average) | Week 2 | -1.14 Units on a scale | Standard Error 0.2 |
Comparison: Week 1: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.2880% CI: [-0.46, 0.04]Mixed Models Analysis
Comparison: Week 2: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.1480% CI: [-0.78, -0.06]Mixed Models Analysis
Secondary
Change From Baseline in Patient's Global Assessment of Arthritic Condition at Week 1 and Week 2
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04136309 | 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 |
| PF-04136309 | 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 |
| Placebo | Change From Baseline in Patient's Global Assessment of Arthritic Condition at Week 1 and Week 2 | Week 1 | -0.32 Units on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline in Patient's Global Assessment of Arthritic Condition at Week 1 and Week 2 | Week 2 | -0.44 Units on a scale | Standard Error 0.09 |
Comparison: Week 1: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.4580% CI: [-0.27, 0.07]Mixed Models Analysis
Comparison: Week 2: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.3780% CI: [-0.29, 0.05]Mixed Models Analysis
Secondary
Change From Baseline in WOMAC Importance Weighted Total Score at Week 1 and Week 2
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04136309 | 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 |
| PF-04136309 | 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 |
| Placebo | Change From Baseline in WOMAC Importance Weighted Total Score at Week 1 and Week 2 | Week 1 | -3.90 Units on a scale | Standard Error 0.65 |
| Placebo | Change From Baseline in WOMAC Importance Weighted Total Score at Week 1 and Week 2 | Week 2 | -4.84 Units on a scale | Standard Error 0.73 |
Comparison: Week 1: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.4880% CI: [-1.81, 0.52]Mixed Models Analysis
Comparison: Week 2: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.2880% CI: [-2.45, 0.2]Mixed Models Analysis
Secondary
Change From Baseline in WOMAC Pain Domain Score at Week 1
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PF-04136309 | Change From Baseline in WOMAC Pain Domain Score at Week 1 | -2.74 Units on a scale | Standard Error 0.37 |
| Placebo | Change From Baseline in WOMAC Pain Domain Score at Week 1 | -2.49 Units on a scale | Standard Error 0.37 |
Comparison: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.6380% CI: [-0.92, 0.42]Mixed Models Analysis
Secondary
Change From Baseline in WOMAC Physical Function Domain Score at Week 1 and Week 2
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04136309 | 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 |
| PF-04136309 | 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 |
| Placebo | Change From Baseline in WOMAC Physical Function Domain Score at Week 1 and Week 2 | Week 1 | -7.25 Units on a scale | Standard Error 1.29 |
| Placebo | Change From Baseline in WOMAC Physical Function Domain Score at Week 1 and Week 2 | Week 2 | -8.90 Units on a scale | Standard Error 1.42 |
Comparison: Week 1: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.4480% CI: [-3.69, 0.94]Mixed Models Analysis
Comparison: Week 2: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.2380% CI: [-5, 0.16]Mixed Models Analysis
Secondary
Change From Baseline in WOMAC Stiffness Domain Score at Week 1 and Week 2
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04136309 | 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 |
| PF-04136309 | Change From Baseline in WOMAC Stiffness Domain Score at Week 1 and Week 2 | Week 2 | -1.39 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in WOMAC Stiffness Domain Score at Week 1 and Week 2 | Week 1 | -0.78 Units on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline in WOMAC Stiffness Domain Score at Week 1 and Week 2 | Week 2 | -1.24 Units on a scale | Standard Error 0.2 |
Comparison: Week 1: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.5480% CI: [-0.51, 0.18]Mixed Models Analysis
Comparison: Week 2: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.680% CI: [-0.51, 0.21]Mixed Models Analysis
Secondary
Change From Baseline in WOMAC Total Score at Week 1 and Week 2
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04136309 | 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 |
| PF-04136309 | 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 |
| Placebo | Change From Baseline in WOMAC Total Score at Week 1 and Week 2 | Week 1 | -10.54 Units on a scale | Standard Error 1.76 |
| Placebo | Change From Baseline in WOMAC Total Score at Week 1 and Week 2 | Week 2 | -13.22 Units on a scale | Standard Error 1.98 |
Comparison: Week 1: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.4880% CI: [-4.94, 1.41]Mixed Models Analysis
Comparison: Week 2: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.p-value: 0.2880% CI: [-6.61, 0.57]Mixed Models Analysis
Secondary
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)
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-04136309 | 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 |
| PF-04136309 | 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 |
| Placebo | 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 | 20 Participants |
| Placebo | 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 | 10 Participants |
Comparison: 30% Reductionp-value: 0.22Cochran-Mantel-Haenszel
Comparison: 50% Reductionp-value: 0.38Cochran-Mantel-Haenszel
Other Pre-specified
Change From Baseline in Absolute Monocyte Count at Day 14
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-04136309 | Change From Baseline in Absolute Monocyte Count at Day 14 | -0.13 Thousand cells per millimeter cube |
| Placebo | Change From Baseline in Absolute Monocyte Count at Day 14 | -0.01 Thousand cells per millimeter cube |
Other Pre-specified
Change From Baseline in Percent Monocytes at Day 14
Monocytes (percent) were derived as monocyte absolute counts per white blood cell absolute counts\*100.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-04136309 | Change From Baseline in Percent Monocytes at Day 14 | -1.7 Percent monocytes |
| Placebo | Change From Baseline in Percent Monocytes at Day 14 | 0.0 Percent monocytes |
Other Pre-specified
Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-04136309 | Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity | Mild | 1 Participants |
| PF-04136309 | Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity | Moderate | 1 Participants |
| PF-04136309 | Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity | Severe | 1 Participants |
| Placebo | Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity | Mild | 1 Participants |
| Placebo | Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity | Moderate | 0 Participants |
| Placebo | Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity | Severe | 0 Participants |
Other Pre-specified
Number of Participants Who Discontinued Due to Treatment Emergent AEs and Treatment Emergent Treatment Related AEs
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-04136309 | Number of Participants Who Discontinued Due to Treatment Emergent AEs and Treatment Emergent Treatment Related AEs | Treatment Emergent AEs | 3 Participants |
| PF-04136309 | Number of Participants Who Discontinued Due to Treatment Emergent AEs and Treatment Emergent Treatment Related AEs | Treatment Emergent Treatment Related AEs | 1 Participants |
| Placebo | Number of Participants Who Discontinued Due to Treatment Emergent AEs and Treatment Emergent Treatment Related AEs | Treatment Emergent AEs | 1 Participants |
| Placebo | Number of Participants Who Discontinued Due to Treatment Emergent AEs and Treatment Emergent Treatment Related AEs | Treatment Emergent Treatment Related AEs | 1 Participants |
Other Pre-specified
Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters
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).
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-04136309 | Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters | Maximum PR Interval increase from baseline; change >=25% | 0 Participants |
| PF-04136309 | Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters | Maximum QRS Complex increase from baseline; change >=25% | 0 Participants |
| PF-04136309 | 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 |
| PF-04136309 | Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters | Maximum QTc Interval increase from baseline; Change >=60 msec | 1 Participants |
| PF-04136309 | 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 |
| PF-04136309 | Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters | Maximum QTcF Interval increase from baseline; Change >=60 msec | 1 Participants |
| Placebo | Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters | Maximum QTcF Interval increase from baseline; Change >=30 msec and < 60 msec | 0 Participants |
| Placebo | Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters | Maximum PR Interval increase from baseline; change >=25% | 0 Participants |
| Placebo | Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters | Maximum QTc Interval increase from baseline; Change >=60 msec | 0 Participants |
| Placebo | Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters | Maximum QRS Complex increase from baseline; change >=25% | 0 Participants |
| Placebo | Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters | Maximum QTcF Interval increase from baseline; Change >=60 msec | 0 Participants |
| Placebo | Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters | Maximum QTc Interval increase from baseline; Change >=30 msec and < 60 msec | 0 Participants |
Other Pre-specified
Number of Participants With Clinically Significant Change From Baseline in Blood Pressure and Pulse Rate
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.
Time frame: From Baseline up to Week 2
Population: FAS included all randomized participants who took at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-04136309 | Number of Participants With Clinically Significant Change From Baseline in Blood Pressure and Pulse Rate | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Change From Baseline in Blood Pressure and Pulse Rate | 0 Participants |
Other Pre-specified
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-04136309 | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment Emergent AEs | 22 Participants |
| PF-04136309 | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment Emergent SAEs | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment Emergent AEs | 21 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment Emergent SAEs | 0 Participants |
Other Pre-specified
Number of Participants With Treatment Emergent Treatment Related AEs and SAEs
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-04136309 | Number of Participants With Treatment Emergent Treatment Related AEs and SAEs | Treatment Emergent Treatment Related AEs | 13 Participants |
| PF-04136309 | Number of Participants With Treatment Emergent Treatment Related AEs and SAEs | Treatment Emergent Treatment Related SAEs | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Treatment Related AEs and SAEs | Treatment Emergent Treatment Related AEs | 16 Participants |
| Placebo | Number of Participants With Treatment Emergent Treatment Related AEs and SAEs | Treatment Emergent Treatment Related SAEs | 0 Participants |
Other Pre-specified
Number of Treatment-Emergent AEs by Severity
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04136309 | Number of Treatment-Emergent AEs by Severity | Moderate | 2 Events |
| PF-04136309 | Number of Treatment-Emergent AEs by Severity | Severe | 2 Events |
| PF-04136309 | Number of Treatment-Emergent AEs by Severity | Mild | 24 Events |
| Placebo | Number of Treatment-Emergent AEs by Severity | Mild | 29 Events |
| Placebo | Number of Treatment-Emergent AEs by Severity | Moderate | 9 Events |
| Placebo | Number of Treatment-Emergent AEs by Severity | Severe | 1 Events |
Other Pre-specified
Number of Treatment-Emergent Treatment-Related AEs by Severity
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04136309 | Number of Treatment-Emergent Treatment-Related AEs by Severity | Mild | 13 Events |
| PF-04136309 | Number of Treatment-Emergent Treatment-Related AEs by Severity | Moderate | 1 Events |
| PF-04136309 | Number of Treatment-Emergent Treatment-Related AEs by Severity | Severe | 1 Events |
| Placebo | Number of Treatment-Emergent Treatment-Related AEs by Severity | Mild | 18 Events |
| Placebo | Number of Treatment-Emergent Treatment-Related AEs by Severity | Moderate | 4 Events |
| Placebo | Number of Treatment-Emergent Treatment-Related AEs by Severity | Severe | 1 Events |
Other Pre-specified
Plasma Concentration Versus Time of PF-04136309
In this outcome measure data for reporting arm PF-04136309 was collected and reported as planned.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04136309 | Plasma Concentration Versus Time of PF-04136309 | Day 1: pre-dose | 257.90 Nanogram per milliliter | Standard Deviation 276.38 |
| PF-04136309 | Plasma Concentration Versus Time of PF-04136309 | Day 1: 6 hours post-dose | 587.54 Nanogram per milliliter | Standard Deviation 626.53 |
| PF-04136309 | Plasma Concentration Versus Time of PF-04136309 | Day 1: 7 hours post-dose | 590.85 Nanogram per milliliter | Standard Deviation 615.06 |
| PF-04136309 | Plasma Concentration Versus Time of PF-04136309 | Day 14: 0 hours pre-dose | 227.42 Nanogram per milliliter | Standard Deviation 259.21 |
| PF-04136309 | Plasma Concentration Versus Time of PF-04136309 | Day 14: 6 hours post-dose | 388.00 Nanogram per milliliter | Standard Deviation 244.98 |
| PF-04136309 | Plasma Concentration Versus Time of PF-04136309 | Day 14: 7 hours post-dose | 426.14 Nanogram per milliliter | Standard Deviation 266.11 |