Peripheral Vascular Disease, Raynaud's Disease
Conditions
Keywords
Raynaud's phenomenon, vasospasm, scleroderma, systemic sclerosis, CREST, phosphodiesterase inhibitor
Brief summary
The investigators propose that once daily administration of PF-00489791, a phosphodiesterase inhibitor, will reduce vasospasm and improve symptoms and signs associated with Primary and Secondary Raynaud's Phenomenon.
Interventions
DRUGPF-00489791
Subjects with Secondary Raynaud's Phenomenon will receive PF-00489791 4 mg once a day for the first 4 week cross over period and then placebo once a day for the second 4 week cross over period
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Active Raynaud's Phenomenon * Stable disease and medication requirements over the previous two months * For Secondary Raynaud's Phenomenon subjects, a diagnosis of scleroderma using the American College of Rheumatology criteria or by the presence of at least 3/5 features of CREST syndrome * both sexes
Exclusion criteria
* Uncontrolled hypertension, diabetes mellitus, angina, or using oral nitrates * Smoking within 3 months or smoking cessation using nicotine products * Subjects currently taking sildenafil, tadalafil or vardenafil * Subjects with ulnar arterial occlusive disease as shown by a modified Allen test * Pregnant or breast feeding or considering pregnancy in next 4 months * Participation in trial for investigational drug within 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Baseline, Week 4 | The Raynaud's Condition score (RCS) is participant's rating of difficulty considering number of attacks, duration, amount of pain, numbness, or other symptoms caused in the fingers (including painful sores) due to the Raynaud's phenomenon every day and impact of Raynaud's alone on use of hands every day. An 11 point Likert scale is used to rate the difficulty caused by the condition each day with 0 = no difficulty and 10 = extreme difficulty. Participants were asked to select the number that best describes their difficulty, with higher score indicating worse condition. Average daily score was considered for participants completing more than 1 Raynaud's pain score scale on a day. Baseline value was calculated as mean of the scores over 7 days prior to treatment start. Week 4 value was calculated as mean of the scores over the 7-day period prior to Week 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Baseline, Week 4 | Mean duration of Raynaud's attacks for a time period was calculated as sum of recorded durations of attacks in the time period divided by total number of attacks in the time period where duration was recorded. |
| Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Baseline, Week 1, 2, 3, 4 | Participants were asked to rate their worst Raynaud's pain in the past 24 hours using an 11 point Likert scale, with 0 = no Raynaud's pain and 10 = the worst possible pain. Highest (most severe) response was considered for participants responding at more than 1 point on the scale. Average daily score was considered for participants completing more than 1 Raynaud's pain score scale on a day. Baseline value was calculated as mean of the scores over 7 days prior to treatment start. Post-baseline value was calculated as mean of the scores over the 7-day period prior to the visit. |
| Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort | Baseline, Day 14, 28 | Presence of ulcer was assessed at baseline. At post-baseline visits, each ulcer was measured and scored: 1= smaller or improved compared to previous visit, 2= same as previous visit, 3= bigger or worse than previous visit, and 4= new. If a new digital ulcer develops during the course of the study, the measurement and scoring were initiated on this additional ulcer. Healed ulcers were not counted into the number of ulcers. Participants with SRP in the per-protocol population with at least 1 digital ulcer present at any assessment were evaluable for this measure. Results are reported for participants with presence of ulcer at baseline and decrease from baseline in ulcers at post-baseline visits. |
| Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Baseline, Week 1, Week 2, Week 3, Week 4 | Change from baseline in the number of Raynaud's attacks at Week 1, Week 2, Week 3 and Week 4 was calculated from the number of attacks reported over the 7-day period prior to each week from the patient diary, respectively. |
| Number of Participants With Laboratory Test Abnormalities | Screening up to 28 days after last study dose (up to 98 days) | Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (less than \[\<\] 0.8\*lower limit of normal\[LLN\]); leukocytes (\<0.6 LLN /greater than \[\>\] 1.5\*upper LN \[ULN\]; platelets (\<0.5\*LLN/\>1.75\*ULN); neutrophils, lymphocytes (\<0.8\* LLN/\>1.2\*ULN); eosinophils, basophils, monocytes (\>1.2\*ULN); bilirubin (\>1.5\*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma GT, alkaline phosphatase (\>3\*ULN); BUN, creatinine (\>1.3\*ULN); glucose (\<0.6 LLN/\>1.5\*ULN); uric acid (\>1.2\*ULN); sodium (\<0.95\*LLN/\>1.05\*ULN); potassium, calcium, chloride, bicarbonate (\<0.9\*LLN/\>1.1\*ULN); albumin, total protein (\<0.8\*LLN/\>1.2\*ULN); creatine kinase (\>2.0\*ULN); Urine Specific Gravity, Urine pH, urine blood, urine glucose, urine protein, urine ketones, urine leukocytes esterase (\>=1 high-powered field). Total number of participants with any laboratory abnormalities was reported. |
| Number of Participants With Clinically Significant Changes in Vital Signs and Orthostatic Blood Pressure Measurements | Screening up to 28 days after last study dose (up to 98 days) | Vital signs assessment included measurement of supine and standing pulse rate, systolic and diastolic blood pressures. Criteria for clinically significant vital signs and orthostatic blood pressure measurements were based on investigator's judgement. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Values | Screening up to 28 days after last study dose (up to 98 days) | ECG assessment included measurement of PR, QRS, QT,corrected QT interval (QTc)values. Criteria for clinically significant ECG values were based on investigator's judgement. |
| Plasma Concentration of PF-00489791 and Its Metabolites | Day 1, 15, 29 (Day 1, 15, 29 for first intervention period), 43, 57, 71 (Day 1, 15, 29 for second intervention period) | Only participants receiving PF-00489791 were to be analyzed for this outcome. Data have been calculated by setting plasma concentration values below the lower limit of quantification to 0. The lower limit of quantification is 0.0100 microgram per milliliter (mcg/mL). Data for plasma concentration of PF-00489791 metabolites was not analyzed, as it was not intended to be a secondary endpoint and was deemed optional. |
Countries
Canada, Colombia, Czechia, Germany, Hungary, Mexico, Poland, South Korea, Spain, Sweden, United States
Participant flow
Pre-assignment details
A total of 243 participants were stratified into 2 cohorts (Primary Raynaud's phenomenon\[PRP\] and secondary RP\[SRP\]), who entered a 2-week placebo run-in period (to establish baseline), followed by a cross-over period (first 4 week treatment period,then a 2 week placebo washout,then 4 week treatment period) and then a 2-week placebo run-out period.
Participants by arm
| Arm | Count |
|---|---|
| PRP Cohort: Placebo First, Then PF-00489791 4 mg Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first intervention period and then PF-00489791 tablets 4 milligram (mg) (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in second intervention period to participants with PRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily. | 27 |
| PRP Cohort: PF-00489791 4mg First, Then Placebo PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first intervention DB period and 2 placebo tablets matched to PF-00489791 orally once daily for 4 weeks in second DB intervention period to participants with PRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily. | 29 |
| PRP Cohort: Placebo First, Then PF-00489791 20 mg Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first intervention period and then PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in second DB intervention period to participants with PRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily. | 29 |
| PRP Cohort: PF-00489791 20 mg First, Then Placebo PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first intervention period and then 2 placebo tablets matched to PF-00489791 orally once daily for 4 weeks in second intervention period to participants with PRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily. | 28 |
| SRP Cohort: Placebo First, Then PF-00489791 4 mg Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first intervention period and then PF-00489791 tablets 4 milligram (mg) (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in second intervention period to participants with SRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily. | 33 |
| SRP Cohort: PF-00489791 4 mg First, Then Placebo PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first intervention period and then 2 placebo tablets matched to PF-00489791 orally once daily for 4 weeks in second intervention period to participants with SRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily. | 32 |
| SRP Cohort: Placebo First, Then PF-00489791 20 mg Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first intervention period and then PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in second intervention period to participants with SRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily. | 32 |
| SRP Cohort: PF-00489791 20 mg First, Then Placebo PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first intervention period and then 2 placebo tablets matched to PF-00489791 orally once daily for 4 weeks in second intervention period to participants with SRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily. | 33 |
| Total | 243 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| First Intervention Period (4 Weeks) | Adverse Event | 0 | 2 | 0 | 3 | 1 | 2 | 0 | 5 |
| First Intervention Period (4 Weeks) | Did not meet inclusion criteria | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 1 |
| First Intervention Period (4 Weeks) | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| First Intervention Period (4 Weeks) | Other | 0 | 0 | 1 | 1 | 2 | 0 | 0 | 0 |
| First Intervention Period (4 Weeks) | Pregnancy | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| First Intervention Period (4 Weeks) | Protocol Violation | 1 | 1 | 1 | 2 | 0 | 0 | 1 | 0 |
| Second Intervention Period (4 Weeks) | Adverse Event | 0 | 0 | 1 | 0 | 1 | 1 | 7 | 1 |
| Second Intervention Period (4 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Second Intervention Period (4 Weeks) | Non-compliance | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Second Intervention Period (4 Weeks) | Other | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Second Intervention Period (4 Weeks) | Protocol Violation | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | PRP Cohort: Placebo First, Then PF-00489791 4 mg | PRP Cohort: PF-00489791 4mg First, Then Placebo | PRP Cohort: Placebo First, Then PF-00489791 20 mg | PRP Cohort: PF-00489791 20 mg First, Then Placebo | SRP Cohort: Placebo First, Then PF-00489791 4 mg | SRP Cohort: PF-00489791 4 mg First, Then Placebo | SRP Cohort: Placebo First, Then PF-00489791 20 mg | SRP Cohort: PF-00489791 20 mg First, Then Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized Between 18 to 44 years | 14 Participants | 12 Participants | 14 Participants | 14 Participants | 10 Participants | 6 Participants | 16 Participants | 9 Participants | 95 Participants |
| Age, Customized Between 45 to 64 years | 13 Participants | 16 Participants | 15 Participants | 14 Participants | 22 Participants | 26 Participants | 16 Participants | 24 Participants | 146 Participants |
| Age, Customized Greater than or equal to (>=) 65 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Female | 25 Participants | 25 Participants | 25 Participants | 26 Participants | 30 Participants | 30 Participants | 31 Participants | 28 Participants | 220 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 4 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 5 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 54 | 0 / 102 | 0 / 61 | 0 / 64 | 1 / 122 |
| other Total, other adverse events | 27 / 55 | 34 / 54 | 43 / 102 | 34 / 61 | 51 / 64 | 60 / 122 |
| serious Total, serious adverse events | 0 / 55 | 0 / 54 | 0 / 102 | 0 / 61 | 0 / 64 | 1 / 122 |
Outcome results
Primary
Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4
The Raynaud's Condition score (RCS) is participant's rating of difficulty considering number of attacks, duration, amount of pain, numbness, or other symptoms caused in the fingers (including painful sores) due to the Raynaud's phenomenon every day and impact of Raynaud's alone on use of hands every day. An 11 point Likert scale is used to rate the difficulty caused by the condition each day with 0 = no difficulty and 10 = extreme difficulty. Participants were asked to select the number that best describes their difficulty, with higher score indicating worse condition. Average daily score was considered for participants completing more than 1 Raynaud's pain score scale on a day. Baseline value was calculated as mean of the scores over 7 days prior to treatment start. Week 4 value was calculated as mean of the scores over the 7-day period prior to Week 4.
Time frame: Baseline, Week 4
Population: Per-protocol analysis set (PPAS) included all randomized participants compliant with diary completion and were not amongst serious protocol violators, receiving study medication till the study completion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00489791 4 mg (PRP) | Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Baseline | 3.04 units on a scale | Standard Deviation 1.899 |
| PF-00489791 4 mg (PRP) | Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Change at Week 4 | -0.76 units on a scale | Standard Deviation 1.901 |
| PF-00489791 20 mg (PRP) | Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Baseline | 2.90 units on a scale | Standard Deviation 2.16 |
| PF-00489791 20 mg (PRP) | Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Change at Week 4 | -1.05 units on a scale | Standard Deviation 1.771 |
| Placebo (PRP) | Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Baseline | 2.98 units on a scale | Standard Deviation 1.958 |
| Placebo (PRP) | Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Change at Week 4 | -0.61 units on a scale | Standard Deviation 1.404 |
| PF-00489791 4 mg (SRP) | Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Baseline | 3.14 units on a scale | Standard Deviation 2.431 |
| PF-00489791 4 mg (SRP) | Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Change at Week 4 | -0.82 units on a scale | Standard Deviation 1.624 |
| PF-00489791 20 mg (SRP) | Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Baseline | 2.53 units on a scale | Standard Deviation 1.833 |
| PF-00489791 20 mg (SRP) | Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Change at Week 4 | -0.15 units on a scale | Standard Deviation 1.09 |
| Placebo (SRP) | Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Baseline | 2.97 units on a scale | Standard Deviation 2.492 |
| Placebo (SRP) | Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 | Change at Week 4 | -0.24 units on a scale | Standard Deviation 1.437 |
Comparison: PRP: Adjusted mean difference analysis was based on Analysis of Covariance (ANCOVA) model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.651380% CI: [-0.21, 0.44]ANCOVA
Comparison: PRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.005780% CI: [-0.99, -0.38]ANCOVA
Comparison: SRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.115780% CI: [-0.8, -0.08]ANCOVA
Comparison: SRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.628680% CI: [-0.56, 0.25]ANCOVA
Secondary
Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4
Mean duration of Raynaud's attacks for a time period was calculated as sum of recorded durations of attacks in the time period divided by total number of attacks in the time period where duration was recorded.
Time frame: Baseline, Week 4
Population: PPAS included all randomized participants compliant with diary completion and were not amongst serious protocol violators, receiving study medication till the study completion. Here, number analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00489791 4 mg (PRP) | Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Baseline | 17.69 minutes per attack | Standard Deviation 13.184 |
| PF-00489791 4 mg (PRP) | Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Change at Week 4 | -2.89 minutes per attack | Standard Deviation 7.48 |
| PF-00489791 20 mg (PRP) | Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Baseline | 22.23 minutes per attack | Standard Deviation 36.562 |
| PF-00489791 20 mg (PRP) | Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Change at Week 4 | -5.63 minutes per attack | Standard Deviation 43.067 |
| Placebo (PRP) | Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Baseline | 19.61 minutes per attack | Standard Deviation 40.603 |
| Placebo (PRP) | Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Change at Week 4 | -1.41 minutes per attack | Standard Deviation 12.348 |
| PF-00489791 4 mg (SRP) | Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Baseline | 19.37 minutes per attack | Standard Deviation 18.929 |
| PF-00489791 4 mg (SRP) | Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Change at Week 4 | -3.92 minutes per attack | Standard Deviation 11.336 |
| PF-00489791 20 mg (SRP) | Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Baseline | 19.07 minutes per attack | Standard Deviation 18.196 |
| PF-00489791 20 mg (SRP) | Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Change at Week 4 | -2.61 minutes per attack | Standard Deviation 9.593 |
| Placebo (SRP) | Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Baseline | 19.91 minutes per attack | Standard Deviation 19.886 |
| Placebo (SRP) | Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 | Change at Week 4 | -1.65 minutes per attack | Standard Deviation 10.609 |
Comparison: PRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.7980% CI: [-4.61, 7.03]ANCOVA
Comparison: PRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.146380% CI: [-11.61, -0.73]ANCOVA
Comparison: SRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.144680% CI: [-4.44, -0.29]ANCOVA
Comparison: SRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.549780% CI: [-3.45, 1.26]ANCOVA
Secondary
Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4
Participants were asked to rate their worst Raynaud's pain in the past 24 hours using an 11 point Likert scale, with 0 = no Raynaud's pain and 10 = the worst possible pain. Highest (most severe) response was considered for participants responding at more than 1 point on the scale. Average daily score was considered for participants completing more than 1 Raynaud's pain score scale on a day. Baseline value was calculated as mean of the scores over 7 days prior to treatment start. Post-baseline value was calculated as mean of the scores over the 7-day period prior to the visit.
Time frame: Baseline, Week 1, 2, 3, 4
Population: PPAS included all randomized participants compliant with diary completion and were not amongst serious protocol violators, receiving study medication till the study completion. Here, number analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00489791 4 mg (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 3 | -0.82 units on a scale | Standard Deviation 1.72 |
| PF-00489791 4 mg (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 1 | -0.72 units on a scale | Standard Deviation 1.525 |
| PF-00489791 4 mg (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Baseline | 2.84 units on a scale | Standard Deviation 2.074 |
| PF-00489791 4 mg (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 4 | -0.80 units on a scale | Standard Deviation 1.842 |
| PF-00489791 4 mg (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 2 | -0.94 units on a scale | Standard Deviation 1.745 |
| PF-00489791 20 mg (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 1 | -0.74 units on a scale | Standard Deviation 1.266 |
| PF-00489791 20 mg (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 3 | -1.12 units on a scale | Standard Deviation 1.664 |
| PF-00489791 20 mg (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Baseline | 2.78 units on a scale | Standard Deviation 2.348 |
| PF-00489791 20 mg (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 4 | -1.14 units on a scale | Standard Deviation 1.82 |
| PF-00489791 20 mg (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 2 | -0.61 units on a scale | Standard Deviation 1.524 |
| Placebo (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 1 | -0.26 units on a scale | Standard Deviation 1.205 |
| Placebo (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 3 | -0.62 units on a scale | Standard Deviation 1.262 |
| Placebo (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 4 | -0.63 units on a scale | Standard Deviation 1.423 |
| Placebo (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 2 | -0.48 units on a scale | Standard Deviation 1.337 |
| Placebo (PRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Baseline | 2.80 units on a scale | Standard Deviation 2.064 |
| PF-00489791 4 mg (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 2 | -0.68 units on a scale | Standard Deviation 1.74 |
| PF-00489791 4 mg (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Baseline | 3.33 units on a scale | Standard Deviation 2.614 |
| PF-00489791 4 mg (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 1 | -0.53 units on a scale | Standard Deviation 1.44 |
| PF-00489791 4 mg (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 3 | -0.80 units on a scale | Standard Deviation 1.836 |
| PF-00489791 4 mg (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 4 | -0.77 units on a scale | Standard Deviation 1.922 |
| PF-00489791 20 mg (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 3 | -0.55 units on a scale | Standard Deviation 1.081 |
| PF-00489791 20 mg (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Baseline | 2.54 units on a scale | Standard Deviation 1.895 |
| PF-00489791 20 mg (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 4 | -0.35 units on a scale | Standard Deviation 1.115 |
| PF-00489791 20 mg (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 1 | -0.32 units on a scale | Standard Deviation 1.276 |
| PF-00489791 20 mg (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 2 | -0.33 units on a scale | Standard Deviation 1.321 |
| Placebo (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Baseline | 3.10 units on a scale | Standard Deviation 2.753 |
| Placebo (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 3 | -0.33 units on a scale | Standard Deviation 1.269 |
| Placebo (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 1 | -0.17 units on a scale | Standard Deviation 1.272 |
| Placebo (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 4 | -0.27 units on a scale | Standard Deviation 1.466 |
| Placebo (SRP) | Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 | Change at Week 2 | -0.24 units on a scale | Standard Deviation 1.306 |
Comparison: Week 4 (PRP): Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.590980% CI: [-0.21, 0.52]ANCOVA
Comparison: Week 4 (PRP): Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.005380% CI: [-1.12, -0.43]ANCOVA
Comparison: Week 4 (SRP): Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.346280% CI: [-0.67, 0.1]ANCOVA
Comparison: Week 4 (SRP): Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.19480% CI: [-0.88, -0.01]ANCOVA
Secondary
Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4
Change from baseline in the number of Raynaud's attacks at Week 1, Week 2, Week 3 and Week 4 was calculated from the number of attacks reported over the 7-day period prior to each week from the patient diary, respectively.
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4
Population: PPAS included all randomized participants compliant with diary completion and were not amongst serious protocol violators, receiving study medication till the study completion. Here, number analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00489791 4 mg (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 3 | -4.66 Raynaud's attacks | Standard Deviation 10.559 |
| PF-00489791 4 mg (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 1 | -3.75 Raynaud's attacks | Standard Deviation 7.494 |
| PF-00489791 4 mg (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Baseline | 22.06 Raynaud's attacks | Standard Deviation 20.587 |
| PF-00489791 4 mg (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 4 | -4.85 Raynaud's attacks | Standard Deviation 13.008 |
| PF-00489791 4 mg (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 2 | -5.30 Raynaud's attacks | Standard Deviation 9.487 |
| PF-00489791 20 mg (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 1 | -2.47 Raynaud's attacks | Standard Deviation 6.477 |
| PF-00489791 20 mg (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 3 | -4.86 Raynaud's attacks | Standard Deviation 5.681 |
| PF-00489791 20 mg (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Baseline | 16.31 Raynaud's attacks | Standard Deviation 10.885 |
| PF-00489791 20 mg (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 4 | -3.07 Raynaud's attacks | Standard Deviation 7.118 |
| PF-00489791 20 mg (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 2 | -2.36 Raynaud's attacks | Standard Deviation 8.371 |
| Placebo (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 1 | -1.41 Raynaud's attacks | Standard Deviation 7.934 |
| Placebo (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 3 | -4.03 Raynaud's attacks | Standard Deviation 10.396 |
| Placebo (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 4 | -3.65 Raynaud's attacks | Standard Deviation 10.46 |
| Placebo (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 2 | -2.45 Raynaud's attacks | Standard Deviation 11.107 |
| Placebo (PRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Baseline | 20.19 Raynaud's attacks | Standard Deviation 17.802 |
| PF-00489791 4 mg (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 2 | -3.76 Raynaud's attacks | Standard Deviation 9.028 |
| PF-00489791 4 mg (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Baseline | 22.80 Raynaud's attacks | Standard Deviation 16.27 |
| PF-00489791 4 mg (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 1 | -3.17 Raynaud's attacks | Standard Deviation 7.994 |
| PF-00489791 4 mg (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 3 | -4.25 Raynaud's attacks | Standard Deviation 11.408 |
| PF-00489791 4 mg (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 4 | -3.89 Raynaud's attacks | Standard Deviation 8.326 |
| PF-00489791 20 mg (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 3 | -3.75 Raynaud's attacks | Standard Deviation 8.601 |
| PF-00489791 20 mg (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Baseline | 23.70 Raynaud's attacks | Standard Deviation 20.909 |
| PF-00489791 20 mg (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 4 | -2.68 Raynaud's attacks | Standard Deviation 10.002 |
| PF-00489791 20 mg (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 1 | -4.49 Raynaud's attacks | Standard Deviation 14.692 |
| PF-00489791 20 mg (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 2 | -4.43 Raynaud's attacks | Standard Deviation 17.312 |
| Placebo (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Baseline | 23.08 Raynaud's attacks | Standard Deviation 20.698 |
| Placebo (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 3 | -1.93 Raynaud's attacks | Standard Deviation 9.487 |
| Placebo (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 1 | -2.36 Raynaud's attacks | Standard Deviation 11.85 |
| Placebo (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 4 | -2.25 Raynaud's attacks | Standard Deviation 10.624 |
| Placebo (SRP) | Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 | Change at Week 2 | -1.87 Raynaud's attacks | Standard Deviation 11.051 |
Comparison: At Week 4 - PRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.950480% CI: [-2.43, 2.68]ANCOVA
Comparison: At Week 4 - PRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.465180% CI: [-3.74, 1.03]ANCOVA
Comparison: At Week 4 - SRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.742380% CI: [-2.92, 1.73]ANCOVA
Comparison: At Week 4 - SRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.p-value: 0.352480% CI: [-4.55, 0.73]ANCOVA
Secondary
Number of Participants With Abnormal Electrocardiogram (ECG) Values
ECG assessment included measurement of PR, QRS, QT,corrected QT interval (QTc)values. Criteria for clinically significant ECG values were based on investigator's judgement.
Time frame: Screening up to 28 days after last study dose (up to 98 days)
Population: Safety analysis set consisted of all participants who took at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-00489791 4 mg (PRP) | Number of Participants With Abnormal Electrocardiogram (ECG) Values | 0 participants |
| PF-00489791 20 mg (PRP) | Number of Participants With Abnormal Electrocardiogram (ECG) Values | 0 participants |
| Placebo (PRP) | Number of Participants With Abnormal Electrocardiogram (ECG) Values | 0 participants |
| PF-00489791 4 mg (SRP) | Number of Participants With Abnormal Electrocardiogram (ECG) Values | 0 participants |
| PF-00489791 20 mg (SRP) | Number of Participants With Abnormal Electrocardiogram (ECG) Values | 0 participants |
| Placebo (SRP) | Number of Participants With Abnormal Electrocardiogram (ECG) Values | 0 participants |
Secondary
Number of Participants With Clinically Significant Changes in Vital Signs and Orthostatic Blood Pressure Measurements
Vital signs assessment included measurement of supine and standing pulse rate, systolic and diastolic blood pressures. Criteria for clinically significant vital signs and orthostatic blood pressure measurements were based on investigator's judgement.
Time frame: Screening up to 28 days after last study dose (up to 98 days)
Population: Safety analysis set consisted of all participants who took at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-00489791 4 mg (PRP) | Number of Participants With Clinically Significant Changes in Vital Signs and Orthostatic Blood Pressure Measurements | 0 participants |
| PF-00489791 20 mg (PRP) | Number of Participants With Clinically Significant Changes in Vital Signs and Orthostatic Blood Pressure Measurements | 0 participants |
| Placebo (PRP) | Number of Participants With Clinically Significant Changes in Vital Signs and Orthostatic Blood Pressure Measurements | 0 participants |
| PF-00489791 4 mg (SRP) | Number of Participants With Clinically Significant Changes in Vital Signs and Orthostatic Blood Pressure Measurements | 0 participants |
| PF-00489791 20 mg (SRP) | Number of Participants With Clinically Significant Changes in Vital Signs and Orthostatic Blood Pressure Measurements | 0 participants |
| Placebo (SRP) | Number of Participants With Clinically Significant Changes in Vital Signs and Orthostatic Blood Pressure Measurements | 0 participants |
Secondary
Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort
Presence of ulcer was assessed at baseline. At post-baseline visits, each ulcer was measured and scored: 1= smaller or improved compared to previous visit, 2= same as previous visit, 3= bigger or worse than previous visit, and 4= new. If a new digital ulcer develops during the course of the study, the measurement and scoring were initiated on this additional ulcer. Healed ulcers were not counted into the number of ulcers. Participants with SRP in the per-protocol population with at least 1 digital ulcer present at any assessment were evaluable for this measure. Results are reported for participants with presence of ulcer at baseline and decrease from baseline in ulcers at post-baseline visits.
Time frame: Baseline, Day 14, 28
Population: PPAS included all randomized participants compliant with diary completion and were not amongst serious protocol violators, receiving study medication till the study completion. Here, number analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-00489791 4 mg (PRP) | Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort | With Decrease at Day 14 | 7 participants |
| PF-00489791 4 mg (PRP) | Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort | Baseline | 10 participants |
| PF-00489791 4 mg (PRP) | Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort | With Decrease at Day 28 | 9 participants |
| PF-00489791 20 mg (PRP) | Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort | With Decrease at Day 14 | 1 participants |
| PF-00489791 20 mg (PRP) | Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort | Baseline | 7 participants |
| PF-00489791 20 mg (PRP) | Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort | With Decrease at Day 28 | 5 participants |
| Placebo (PRP) | Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort | Baseline | 16 participants |
| Placebo (PRP) | Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort | With Decrease at Day 28 | 7 participants |
| Placebo (PRP) | Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort | With Decrease at Day 14 | 6 participants |
Secondary
Number of Participants With Laboratory Test Abnormalities
Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (less than \[\<\] 0.8\*lower limit of normal\[LLN\]); leukocytes (\<0.6 LLN /greater than \[\>\] 1.5\*upper LN \[ULN\]; platelets (\<0.5\*LLN/\>1.75\*ULN); neutrophils, lymphocytes (\<0.8\* LLN/\>1.2\*ULN); eosinophils, basophils, monocytes (\>1.2\*ULN); bilirubin (\>1.5\*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma GT, alkaline phosphatase (\>3\*ULN); BUN, creatinine (\>1.3\*ULN); glucose (\<0.6 LLN/\>1.5\*ULN); uric acid (\>1.2\*ULN); sodium (\<0.95\*LLN/\>1.05\*ULN); potassium, calcium, chloride, bicarbonate (\<0.9\*LLN/\>1.1\*ULN); albumin, total protein (\<0.8\*LLN/\>1.2\*ULN); creatine kinase (\>2.0\*ULN); Urine Specific Gravity, Urine pH, urine blood, urine glucose, urine protein, urine ketones, urine leukocytes esterase (\>=1 high-powered field). Total number of participants with any laboratory abnormalities was reported.
Time frame: Screening up to 28 days after last study dose (up to 98 days)
Population: Analysis population included all randomized participants who took at least 1 dose of study medication along with at least 1 on-treatment laboratory test result.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-00489791 4 mg (PRP) | Number of Participants With Laboratory Test Abnormalities | 2 participants |
| PF-00489791 20 mg (PRP) | Number of Participants With Laboratory Test Abnormalities | 4 participants |
| Placebo (PRP) | Number of Participants With Laboratory Test Abnormalities | 14 participants |
| PF-00489791 4 mg (SRP) | Number of Participants With Laboratory Test Abnormalities | 5 participants |
| PF-00489791 20 mg (SRP) | Number of Participants With Laboratory Test Abnormalities | 13 participants |
| Placebo (SRP) | Number of Participants With Laboratory Test Abnormalities | 10 participants |
Secondary
Plasma Concentration of PF-00489791 and Its Metabolites
Only participants receiving PF-00489791 were to be analyzed for this outcome. Data have been calculated by setting plasma concentration values below the lower limit of quantification to 0. The lower limit of quantification is 0.0100 microgram per milliliter (mcg/mL). Data for plasma concentration of PF-00489791 metabolites was not analyzed, as it was not intended to be a secondary endpoint and was deemed optional.
Time frame: Day 1, 15, 29 (Day 1, 15, 29 for first intervention period), 43, 57, 71 (Day 1, 15, 29 for second intervention period)
Population: Analysis population included participants who received 1 dose of study drug and were analyzed for pharmacokinetic parameters. Here, Overall number of participants signifies participants evaluable for either first or second intervention period and number analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00489791 4 mg (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 1 | 0.0058 mcg/mL | Standard Deviation 0.0314 |
| PF-00489791 4 mg (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 15 | 0.1523 mcg/mL | Standard Deviation 0.0855 |
| PF-00489791 4 mg (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 29 | 0.1489 mcg/mL | Standard Deviation 0.0854 |
| PF-00489791 4 mg (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 43 | NA mcg/mL | — |
| PF-00489791 4 mg (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 57 | 0.1088 mcg/mL | Standard Deviation 0.0629 |
| PF-00489791 4 mg (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 71 | 0.1178 mcg/mL | Standard Deviation 0.0614 |
| PF-00489791 20 mg (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 71 | 0.6337 mcg/mL | Standard Deviation 0.3745 |
| PF-00489791 20 mg (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 43 | NA mcg/mL | — |
| PF-00489791 20 mg (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 1 | NA mcg/mL | — |
| PF-00489791 20 mg (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 29 | 0.6525 mcg/mL | Standard Deviation 0.3822 |
| PF-00489791 20 mg (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 15 | 0.5907 mcg/mL | Standard Deviation 0.3736 |
| PF-00489791 20 mg (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 57 | 0.6890 mcg/mL | Standard Deviation 0.4318 |
| Placebo (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 15 | 0.1756 mcg/mL | Standard Deviation 0.09038 |
| Placebo (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 29 | 0.1776 mcg/mL | Standard Deviation 0.08508 |
| Placebo (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 43 | NA mcg/mL | — |
| Placebo (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 71 | 0.1224 mcg/mL | Standard Deviation 0.0638 |
| Placebo (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 57 | 0.1167 mcg/mL | Standard Deviation 0.05644 |
| Placebo (PRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 1 | NA mcg/mL | — |
| PF-00489791 4 mg (SRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 57 | 0.7565 mcg/mL | Standard Deviation 0.6224 |
| PF-00489791 4 mg (SRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 71 | 0.6639 mcg/mL | Standard Deviation 0.5834 |
| PF-00489791 4 mg (SRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 15 | 0.7718 mcg/mL | Standard Deviation 0.4991 |
| PF-00489791 4 mg (SRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 43 | NA mcg/mL | — |
| PF-00489791 4 mg (SRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 1 | NA mcg/mL | — |
| PF-00489791 4 mg (SRP) | Plasma Concentration of PF-00489791 and Its Metabolites | Day 29 | 0.7577 mcg/mL | Standard Deviation 0.4137 |