Huntington's Disease
Conditions
Keywords
Huntington; chorea; total motor score; CAG repeat: total functional capacity; motor cognitive and behavioral symptoms
Brief summary
This study is a 26 week, randomized, parallel group, double blind comparison of PF-02545920 5 mg, PF-02545920 20 mg, and placebo dosed BID in the treatment of motor impairment of subjects with Huntington's Disease. A total of approximately 260 subjects are planned to be randomized in the study. Primary endpoint is the change from baseline in the Total Motor Score (TMS) assessment of the Unified Huntington Disease Rating Scale (UHDRS) after 26 weeks of treatment. secondary endpoints will include change from baseline in the Total Maximum Chorea (TMC) score of the UHDRS after 13 and 26 weeks of treatment and Clinical Global Impression-Improvement score after 13 and 26 weeks of treatment.
Interventions
DRUGPF-02545920
20 mg twice a day (BID) for 26 weeks. Each 20 mg dose will be taken as 4 tablets of 5 mg. The 20mg dose will be titrated as follow: 5mg BID for 7 days, 10mg BID for 7 days, 15 mg BID for 7 days and 20 mg BID to week 26. Study drug will be provided in weekly blister cards.
OTHERPlacebo
Matching Placebo twice a day (BID) for 26 weeks. Each placebo dose will be taken as 4 tablets of matching Placebo. The placebo dose will not be titrated. Matching placebo will be provided in weekly blister cards.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* CAG repeat equal or greater than 36; * Total motor score equal or greater than 10; * Total functional capacity equal or greater than 7.
Exclusion criteria
* Clinically significant neurologic disorder other than Huntington's disease; * Other severe acute psychiatric conditions, mania and/or psychosis; * History of neutropenia, and myeloproliferative disorders;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Total Motor Score (TMS) Assessment of the Unified Huntington Disease Rating Scale (UHDRS) After 26 Weeks of Treatment. | Baseline, Week 26 | The UHDRS was a clinical rating scale which has been developed by the Huntington Disease Study Group (HSG) to provide a uniform assessment of the clinical features and course of Huntington's Disease (HD). The components of the full UHDRS assess motor function, cognition, behavior and functional abilities. The total motor score (TMS) assessed motor features of HD with standardized ratings of oculomotor function, dysarthria, chorea, dystonia, gait, and postural stability. Some items (such as chorea and dystonia) required grading each extremity (face, bucco-oral-lingual, and trunk) separately. Eye movements require both horizontal and vertical grades. The total motor impairment scores was the sum of all the individual 31 motor sub-items (each rated from 0 to 4), with higher scores indicating more severe motor impairment than lower scores. The range of TMS is 0-124. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192) | Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. |
| Number of Participants With Serious Adverse Events | Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192) | Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormalities) | Screening, Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192) | Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes);coagulation (PT international ratio); liver function (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma GT, LDH, alkaline phosphatase, total protein, albumin); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (calcium, sodium, potassium, chloride, total bicarbonate, magnesium, phosphate); clinical chemistry (glucose, glycosylated, hemoglobin, human chorionic gonadotropin, creatine kinase); urinalysis (decimal logarithm of reciprocal of hydrogen ion activity \[pH\], urine specific gravity, glucose, protein, blood, ketones, nitrite). |
| Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Screening, Day 1, 28, 91, and 182 | Number of participants with ECG meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)\>= 25/50%; Criterion B: maximum QRS complex increase from baseline PctChg \>=50%; Criterion C: maximum QTcF interval (Fridericia's correction) increase from baseline 30\<=change\<60 msec; Criterion D: maximum QTcF interval (Fridericia's correction) increase from baseline change \>=60 msec. |
| Number of Participants With Laboratory Test Abnormalities (With Normal Baseline) | Screening, Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192) | Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes);coagulation (PT international ratio); liver function (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma GT, LDH, alkaline phosphatase, total protein, albumin); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (calcium, sodium, potassium, chloride, total bicarbonate, magnesium, phosphate); clinical chemistry (glucose, glycosylated, hemoglobin, human chorionic gonadotropin, creatine kinase); urinalysis (decimal logarithm of reciprocal of hydrogen ion activity \[pH\], urine specific gravity, glucose, protein, blood, ketones, nitrite). |
| Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Screening, Day 1, 28, 91, and 182 | Absolute values were analyzed for supine systolic blood pressure (SBP), standing SBP, supine diastolic blood pressure (DBP), standing DBP, supine pulse rate, and standing pulse rate. Number of participants with vital signs data meeting the following criteria was reported: Criterion A: supine SBP less than (\<) 90 millimeter of mercury(mmHg); Criterion B: standing SBP \< 90 mmHg; Criterion C: supine DBP \<50 mmHg; Criterion D: standing DBP \<50 mmHg; Criterion E: supine pulse rate \< 40 beats per minute(BPM); Criterion F: supine pulse rate greater than (\>)120 BPM; Criterion G: standing pulse rate \< 40 beats per minute(BPM); Criterion H: standing pulse rate \>120 BPM; |
| Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Screening, Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192) | The criteria for temporary study suspension was as follow: Criterion A: WBC count \<=3000 cells/mm3 but \>= 2000 cells/mm3 or ANC \<= 1500 cells/mm3 but \>= 1000 cells/mm3; Criterion B: WBC \<= 2000 cells/mm3 or ANC \<= 1000 cells/mm3; Criterion C: participants who are discontinued or permanently suspended due to WBC or ANC findings; Criterion D: ANC \<= 500 cells/mm3 |
| Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Screening, Day 1, 28, 91, and 182 | The number of participants with vital signs data of maximum decrease from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in supine SBP \>= 30 mmHg; Criterion B: maximum decrease from baseline in standing SBP \>= 30 mmHg; Criterion C: maximum decrease from baseline in supine DBP \>=20 mmHg; Criterion D: maximum decrease from baseline in standing DBP \>=20 mmHg |
| Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Screening, Day 1, 28, 91, and 182 | The number of participants with ECG absolute values meeting the following criteria was reported: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) \>=300 msec; Criterion B: maximum QRS complex(time from Q wave to the end of S wave, corresponding to ventricle depolarization) \>=140 msec; Criterion C: maximum QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula) 450-\<480 msec; Criterion D: maximum QTcF interval 480-\<500 msec; Criterion E: maximum QTcF interval (Fridericia's correction) \>=500 msec |
| Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192) | Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity; mild (not causing any significant problem, dose adjustment not required), moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event) and severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event). EPS were reported AEs of dystonia and akathisia. |
| Change From Baseline in the Total Maximum Chorea (TMC) Score of the UHDRS After 13 and 26 Weeks of Treatment. | Baseline, Week 13, Week 26 | The UHDRS was a clinical rating scale which has been developed by the Huntington Disease Study Group (HSG) to provide a uniform assessment of the clinical features and course of HD. The components of the full UHDRS assess motor function, cognition, behavior and functional abilities. The Total Maximum Chorea (TMC) was a subset of the TMS assessment. It was composed of the scoring of 7 chorea assessments (face, orobuccolingual, trunk, right and left upper extremities, right and left lower extremities). Each assessment was rated from 0 to 4 (absent to prolonged). TMC is obtained by adding up each of the separate scores, leading to max score of 28. The minimum score is 0. The higher the score, the worse the symptoms. n is the number of evaluable subjects in each visit. |
| Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192) | The C-SSRS captured the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt; preparatory acts towards imminent suicidal behavior; suicidal ideation; self-injurious behavior, no suicidal intent. The results presented are the number of participants with completed suicide or non-fatal suicide events or behaviors. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline. |
| Clinical Global Impression of Improvement (CGI-I) Scale Score After 13 and 26 Weeks of Treatment. | Week 13 & Week 26 | CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Clinician responded to a question: Compared to your subject's condition at the beginning of treatment, how much has your subject changed?. Improvement was compared to baseline and was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. n is the number of evaluable participants in each visit. |
| Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Screening, Day 1, 28, 91, and 182 | The number of participants with vital signs data of maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in supine SBP greater than or equal to (\>=) 30 mmHg; Criterion B: maximum increase from baseline in standing SBP \>= 30 mmHg; Criterion C: maximum increase from baseline in supine DBP \>=20 mmHg; Criterion D: maximum increase from baseline in standing DBP \>=20 mmHg |
Countries
Canada, Germany, Poland, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 272 subjects (133 males and 139 females) were randomized and assigned study treatment.
Participants by arm
| Arm | Count |
|---|---|
| PF-02545920 5 mg BID Participants took 4 tablets packaged in blister packs (3 placebo tablets and one 5 mg PF-02545920) twice a day approximately every 12 hours from Baseline Day 1 (V2) to Week 26 (V9), at approximately the same time of day throughout the study. Study medication was swallowed whole, and was not manipulated or chewed prior to swallowing. | 95 |
| Placebo Participants took 4 tablets of placebo packaged in blister packs twice a day approximately every 12 hours, at approximately the same time of day throughout the study. Study medication was swallowed whole, and was not manipulated or chewed prior to swallowing. | 88 |
| PF-02545920 20 mg BID The 20 mg BID dose of PF-02545920 was titrated as follows: 5 mg BID for 7 days, 10 mg BID for 7 days, 15 mg BID for 7 days, then 20 mg BID for the remainder of the treatment phase. Participants took 4 tablets packaged in blister packs twice a day approximately every 12 hours, at approximately the same time of day throughout the study. The blister packs contained 3 placebo tablets and one 5 mg PF-02545920 tablet for Days 1-7, 2 placebo tablets and two 5 mg PF-02545920 tablets for Days 8-14, 1 placebo tablet and three 5 mg PF-02545920 tablets for Days 15-21, and four 5 mg PF-02545920 tablets from Day 22 through Day 182. Study medication was swallowed whole, and was not manipulated or chewed prior to swallowing. | 87 |
| Total | 270 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 13 | 4 | 23 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Does not meet entrance criteria | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 |
| Overall Study | Other | 1 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 4 |
Baseline characteristics
| Characteristic | PF-02545920 5 mg BID | Placebo | PF-02545920 20 mg BID | Total |
|---|---|---|---|---|
| Age, Continuous | 48.3 years STANDARD_DEVIATION 8.6 | 50.2 years STANDARD_DEVIATION 9.4 | 48.4 years STANDARD_DEVIATION 9.2 | 48.9 years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 42 Participants | 54 Participants | 43 Participants | 139 Participants |
| Sex: Female, Male Male | 53 Participants | 34 Participants | 44 Participants | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 71 / 95 | 42 / 88 | 65 / 87 |
| serious Total, serious adverse events | 2 / 95 | 7 / 88 | 8 / 87 |
Outcome results
Primary
Change From Baseline in the Total Motor Score (TMS) Assessment of the Unified Huntington Disease Rating Scale (UHDRS) After 26 Weeks of Treatment.
The UHDRS was a clinical rating scale which has been developed by the Huntington Disease Study Group (HSG) to provide a uniform assessment of the clinical features and course of Huntington's Disease (HD). The components of the full UHDRS assess motor function, cognition, behavior and functional abilities. The total motor score (TMS) assessed motor features of HD with standardized ratings of oculomotor function, dysarthria, chorea, dystonia, gait, and postural stability. Some items (such as chorea and dystonia) required grading each extremity (face, bucco-oral-lingual, and trunk) separately. Eye movements require both horizontal and vertical grades. The total motor impairment scores was the sum of all the individual 31 motor sub-items (each rated from 0 to 4), with higher scores indicating more severe motor impairment than lower scores. The range of TMS is 0-124.
Time frame: Baseline, Week 26
Population: All participants who have been randomized and have taken at least one dose of PF-02545920 or placebo. Participants without post-dose measurements did not contribute to the analysis, except in the description of the baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02545920 20 mg BID | Change From Baseline in the Total Motor Score (TMS) Assessment of the Unified Huntington Disease Rating Scale (UHDRS) After 26 Weeks of Treatment. | 0.4 units on a scale | Standard Deviation 8.63 |
| PF-02545920 5 mg BID | Change From Baseline in the Total Motor Score (TMS) Assessment of the Unified Huntington Disease Rating Scale (UHDRS) After 26 Weeks of Treatment. | -0.8 units on a scale | Standard Deviation 7.3 |
| Placebo | Change From Baseline in the Total Motor Score (TMS) Assessment of the Unified Huntington Disease Rating Scale (UHDRS) After 26 Weeks of Treatment. | -1.4 units on a scale | Standard Deviation 6.67 |
p-value: 0.203390% CI: [-0.45, 3.49]MMRM
p-value: 0.754990% CI: [-2.2, 1.5]MMRM
Secondary
Change From Baseline in the Total Maximum Chorea (TMC) Score of the UHDRS After 13 and 26 Weeks of Treatment.
The UHDRS was a clinical rating scale which has been developed by the Huntington Disease Study Group (HSG) to provide a uniform assessment of the clinical features and course of HD. The components of the full UHDRS assess motor function, cognition, behavior and functional abilities. The Total Maximum Chorea (TMC) was a subset of the TMS assessment. It was composed of the scoring of 7 chorea assessments (face, orobuccolingual, trunk, right and left upper extremities, right and left lower extremities). Each assessment was rated from 0 to 4 (absent to prolonged). TMC is obtained by adding up each of the separate scores, leading to max score of 28. The minimum score is 0. The higher the score, the worse the symptoms. n is the number of evaluable subjects in each visit.
Time frame: Baseline, Week 13, Week 26
Population: All participants who have been randomized and have taken at least one dose of PF-02545920 or placebo. Participants without post-dose measurements did not contribute to the analysis, except in the description of the baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-02545920 20 mg BID | Change From Baseline in the Total Maximum Chorea (TMC) Score of the UHDRS After 13 and 26 Weeks of Treatment. | Week 13 | 1.1 units on a scale | Standard Deviation 3.92 |
| PF-02545920 20 mg BID | Change From Baseline in the Total Maximum Chorea (TMC) Score of the UHDRS After 13 and 26 Weeks of Treatment. | Week 26 | 0.7 units on a scale | Standard Deviation 3.81 |
| PF-02545920 5 mg BID | Change From Baseline in the Total Maximum Chorea (TMC) Score of the UHDRS After 13 and 26 Weeks of Treatment. | Week 13 | -0.2 units on a scale | Standard Deviation 3.5 |
| PF-02545920 5 mg BID | Change From Baseline in the Total Maximum Chorea (TMC) Score of the UHDRS After 13 and 26 Weeks of Treatment. | Week 26 | -0.4 units on a scale | Standard Deviation 2.84 |
| Placebo | Change From Baseline in the Total Maximum Chorea (TMC) Score of the UHDRS After 13 and 26 Weeks of Treatment. | Week 13 | -0.9 units on a scale | Standard Deviation 2.56 |
| Placebo | Change From Baseline in the Total Maximum Chorea (TMC) Score of the UHDRS After 13 and 26 Weeks of Treatment. | Week 26 | -0.8 units on a scale | Standard Deviation 2.79 |
Comparison: Week 13p-value: 0.00390% CI: [0.69, 2.39]MMRM
Comparison: Week 13p-value: 0.465690% CI: [-0.45, 1.17]MMRM
Comparison: Week 26p-value: 0.014990% CI: [0.39, 2.02]MMRM
Comparison: Week 26p-value: 0.823390% CI: [-0.66, 0.86]MMRM
Secondary
Clinical Global Impression of Improvement (CGI-I) Scale Score After 13 and 26 Weeks of Treatment.
CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Clinician responded to a question: Compared to your subject's condition at the beginning of treatment, how much has your subject changed?. Improvement was compared to baseline and was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. n is the number of evaluable participants in each visit.
Time frame: Week 13 & Week 26
Population: All participants who have been randomized and have taken at least one dose of PF-02545920 or placebo. Participants without post-dose measurements will not contribute to the analysis, except in the description of the baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-02545920 20 mg BID | Clinical Global Impression of Improvement (CGI-I) Scale Score After 13 and 26 Weeks of Treatment. | Week 26 | 3.9 units on a scale | Standard Deviation 1.13 |
| PF-02545920 20 mg BID | Clinical Global Impression of Improvement (CGI-I) Scale Score After 13 and 26 Weeks of Treatment. | Week 13 | 4.0 units on a scale | Standard Deviation 1 |
| PF-02545920 5 mg BID | Clinical Global Impression of Improvement (CGI-I) Scale Score After 13 and 26 Weeks of Treatment. | Week 13 | 3.7 units on a scale | Standard Deviation 0.9 |
| PF-02545920 5 mg BID | Clinical Global Impression of Improvement (CGI-I) Scale Score After 13 and 26 Weeks of Treatment. | Week 26 | 3.8 units on a scale | Standard Deviation 0.99 |
| Placebo | Clinical Global Impression of Improvement (CGI-I) Scale Score After 13 and 26 Weeks of Treatment. | Week 13 | 3.6 units on a scale | Standard Deviation 0.83 |
| Placebo | Clinical Global Impression of Improvement (CGI-I) Scale Score After 13 and 26 Weeks of Treatment. | Week 26 | 3.8 units on a scale | Standard Deviation 0.91 |
Comparison: Week 13p-value: 0.018190% CI: [0.11, 0.6]MMRM
Comparison: Week 13p-value: 0.713390% CI: [-0.18, 0.28]MMRM
Comparison: Week 26p-value: 0.465790% CI: [-0.15, 0.39]MMRM
Comparison: Week 26p-value: 0.833990% CI: [-0.22, 0.28]MMRM
Secondary
Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria
The criteria for temporary study suspension was as follow: Criterion A: WBC count \<=3000 cells/mm3 but \>= 2000 cells/mm3 or ANC \<= 1500 cells/mm3 but \>= 1000 cells/mm3; Criterion B: WBC \<= 2000 cells/mm3 or ANC \<= 1000 cells/mm3; Criterion C: participants who are discontinued or permanently suspended due to WBC or ANC findings; Criterion D: ANC \<= 500 cells/mm3
Time frame: Screening, Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Population: All participants with at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| PF-02545920 20 mg BID | Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Criterion A | 0 participants | 8.63 |
| PF-02545920 20 mg BID | Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Criterion B | 0 participants | — |
| PF-02545920 20 mg BID | Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Criterion C | 0 participants | — |
| PF-02545920 20 mg BID | Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Criterion D | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Criterion D | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Criterion A | 1 participants | 7.3 |
| PF-02545920 5 mg BID | Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Criterion C | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Criterion B | 0 participants | — |
| Placebo | Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Criterion D | 0 participants | — |
| Placebo | Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Criterion B | 0 participants | — |
| Placebo | Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Criterion C | 0 participants | — |
| Placebo | Number of Participants That Met White Blood Count (WBC) and Absolute Neutrophil Count (ANC) Stopping Criteria | Criterion A | 0 participants | 6.67 |
Secondary
Number of Participants With Adverse Events
Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time frame: Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Population: All participants with at least one dose of study medication.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| PF-02545920 20 mg BID | Number of Participants With Adverse Events | 76 participants | 8.63 |
| PF-02545920 5 mg BID | Number of Participants With Adverse Events | 82 participants | 7.3 |
| Placebo | Number of Participants With Adverse Events | 63 participants | 6.67 |
Secondary
Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values)
The number of participants with ECG absolute values meeting the following criteria was reported: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) \>=300 msec; Criterion B: maximum QRS complex(time from Q wave to the end of S wave, corresponding to ventricle depolarization) \>=140 msec; Criterion C: maximum QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula) 450-\<480 msec; Criterion D: maximum QTcF interval 480-\<500 msec; Criterion E: maximum QTcF interval (Fridericia's correction) \>=500 msec
Time frame: Screening, Day 1, 28, 91, and 182
Population: All participants with at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| PF-02545920 20 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion D | 0 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion C | 5 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion A | 0 participants | 8.63 |
| PF-02545920 20 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion B | 0 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion E | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion C | 2 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion A | 0 participants | 7.3 |
| PF-02545920 5 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion B | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion D | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion E | 0 participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion E | 0 participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion D | 0 participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion A | 0 participants | 6.67 |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion C | 7 participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Absolute Values) | Criterion B | 0 participants | — |
Secondary
Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline)
Number of participants with ECG meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)\>= 25/50%; Criterion B: maximum QRS complex increase from baseline PctChg \>=50%; Criterion C: maximum QTcF interval (Fridericia's correction) increase from baseline 30\<=change\<60 msec; Criterion D: maximum QTcF interval (Fridericia's correction) increase from baseline change \>=60 msec.
Time frame: Screening, Day 1, 28, 91, and 182
Population: All participants with at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| PF-02545920 20 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Criterion A | 0 participants | 8.63 |
| PF-02545920 20 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Criterion B | 0 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Criterion C | 4 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Criterion D | 1 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Criterion D | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Criterion A | 0 participants | 7.3 |
| PF-02545920 5 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Criterion C | 4 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Criterion B | 0 participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Criterion D | 0 participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Criterion B | 0 participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Criterion C | 6 participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data That Met Criteria for Potential Clinical Concern(Increase From Baseline) | Criterion A | 0 participants | 6.67 |
Secondary
Number of Participants With Laboratory Test Abnormalities (With Normal Baseline)
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes);coagulation (PT international ratio); liver function (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma GT, LDH, alkaline phosphatase, total protein, albumin); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (calcium, sodium, potassium, chloride, total bicarbonate, magnesium, phosphate); clinical chemistry (glucose, glycosylated, hemoglobin, human chorionic gonadotropin, creatine kinase); urinalysis (decimal logarithm of reciprocal of hydrogen ion activity \[pH\], urine specific gravity, glucose, protein, blood, ketones, nitrite).
Time frame: Screening, Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Population: All participants with at least one dose of study medication.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| PF-02545920 20 mg BID | Number of Participants With Laboratory Test Abnormalities (With Normal Baseline) | 40 participants | 8.63 |
| PF-02545920 5 mg BID | Number of Participants With Laboratory Test Abnormalities (With Normal Baseline) | 36 participants | 7.3 |
| Placebo | Number of Participants With Laboratory Test Abnormalities (With Normal Baseline) | 41 participants | 6.67 |
Secondary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormalities)
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes);coagulation (PT international ratio); liver function (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma GT, LDH, alkaline phosphatase, total protein, albumin); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (calcium, sodium, potassium, chloride, total bicarbonate, magnesium, phosphate); clinical chemistry (glucose, glycosylated, hemoglobin, human chorionic gonadotropin, creatine kinase); urinalysis (decimal logarithm of reciprocal of hydrogen ion activity \[pH\], urine specific gravity, glucose, protein, blood, ketones, nitrite).
Time frame: Screening, Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Population: All participants with at least one dose of study medication.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| PF-02545920 20 mg BID | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormalities) | 47 participants | 8.63 |
| PF-02545920 5 mg BID | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormalities) | 46 participants | 7.3 |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormalities) | 48 participants | 6.67 |
Secondary
Number of Participants With Serious Adverse Events
Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly.
Time frame: Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Population: All participants with at least one dose of study medication.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| PF-02545920 20 mg BID | Number of Participants With Serious Adverse Events | 8 participants | 8.63 |
| PF-02545920 5 mg BID | Number of Participants With Serious Adverse Events | 2 participants | 7.3 |
| Placebo | Number of Participants With Serious Adverse Events | 7 participants | 6.67 |
Secondary
Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit
The C-SSRS captured the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt; preparatory acts towards imminent suicidal behavior; suicidal ideation; self-injurious behavior, no suicidal intent. The results presented are the number of participants with completed suicide or non-fatal suicide events or behaviors. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.
Time frame: Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Population: All participants with at least one dose of study medication.n is the number of evaluable participants in each visit
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| PF-02545920 20 mg BID | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Imminent Suicidal Behavior | 1 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Suicide Attempt | 1 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Self-Injurious Behavior, No Suicidal Attempt | 1 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Completed Suicide | 0 participants | 8.63 |
| PF-02545920 20 mg BID | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Suicidal Ideation | 7 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Suicide Attempt | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Self-Injurious Behavior, No Suicidal Attempt | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Completed Suicide | 0 participants | 7.3 |
| PF-02545920 5 mg BID | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Imminent Suicidal Behavior | 1 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Suicidal Ideation | 5 participants | — |
| Placebo | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Suicidal Ideation | 4 participants | — |
| Placebo | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Imminent Suicidal Behavior | 0 participants | — |
| Placebo | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Self-Injurious Behavior, No Suicidal Attempt | 0 participants | — |
| Placebo | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Suicide Attempt | 0 participants | — |
| Placebo | Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Follow-up Visit | Completed Suicide | 0 participants | 6.67 |
Secondary
Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values)
Absolute values were analyzed for supine systolic blood pressure (SBP), standing SBP, supine diastolic blood pressure (DBP), standing DBP, supine pulse rate, and standing pulse rate. Number of participants with vital signs data meeting the following criteria was reported: Criterion A: supine SBP less than (\<) 90 millimeter of mercury(mmHg); Criterion B: standing SBP \< 90 mmHg; Criterion C: supine DBP \<50 mmHg; Criterion D: standing DBP \<50 mmHg; Criterion E: supine pulse rate \< 40 beats per minute(BPM); Criterion F: supine pulse rate greater than (\>)120 BPM; Criterion G: standing pulse rate \< 40 beats per minute(BPM); Criterion H: standing pulse rate \>120 BPM;
Time frame: Screening, Day 1, 28, 91, and 182
Population: All participants with at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion C | 2 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion G | 0 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion A | 1 participants | 8.63 |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion B | 3 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion D | 1 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion E | 0 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion F | 0 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion H | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion F | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion C | 1 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion D | 3 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion E | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion G | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion H | 0 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion A | 0 participants | 7.3 |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion B | 2 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion G | 0 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion B | 3 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion E | 0 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion C | 1 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion F | 1 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion A | 0 participants | 6.67 |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion D | 0 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Absolute Values) | Criterion H | 0 participants | — |
Secondary
Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline)
The number of participants with vital signs data of maximum decrease from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in supine SBP \>= 30 mmHg; Criterion B: maximum decrease from baseline in standing SBP \>= 30 mmHg; Criterion C: maximum decrease from baseline in supine DBP \>=20 mmHg; Criterion D: maximum decrease from baseline in standing DBP \>=20 mmHg
Time frame: Screening, Day 1, 28, 91, and 182
Population: All participants with at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Criterion C | 8 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Criterion B | 9 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Criterion D | 10 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Criterion A | 1 participants | 8.63 |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Criterion B | 8 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Criterion D | 14 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Criterion A | 7 participants | 7.3 |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Criterion C | 6 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Criterion A | 3 participants | 6.67 |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Criterion D | 9 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Criterion C | 8 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Decrease From Baseline) | Criterion B | 9 participants | — |
Secondary
Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline)
The number of participants with vital signs data of maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in supine SBP greater than or equal to (\>=) 30 mmHg; Criterion B: maximum increase from baseline in standing SBP \>= 30 mmHg; Criterion C: maximum increase from baseline in supine DBP \>=20 mmHg; Criterion D: maximum increase from baseline in standing DBP \>=20 mmHg
Time frame: Screening, Day 1, 28, 91, and 182
Population: All participants with at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Criterion A | 4 participants | 8.63 |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Criterion B | 7 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Criterion C | 3 participants | — |
| PF-02545920 20 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Criterion D | 3 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Criterion D | 8 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Criterion A | 1 participants | 7.3 |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Criterion C | 3 participants | — |
| PF-02545920 5 mg BID | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Criterion B | 8 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Criterion D | 9 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Criterion B | 6 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Criterion C | 10 participants | — |
| Placebo | Number of Participants With Vital Sign Data That Met Criteria for Potential Clinical Concern (Increase From Baseline) | Criterion A | 4 participants | 6.67 |
Secondary
Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia
Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity; mild (not causing any significant problem, dose adjustment not required), moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event) and severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event). EPS were reported AEs of dystonia and akathisia.
Time frame: Day 1, 7, 14, 28, 56, 91, 133, 182 and follow-up visits (from Day 189 to 192)
Population: All participants with at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| PF-02545920 20 mg BID | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Dystonia(Mild) | 0 participants | 8.63 |
| PF-02545920 20 mg BID | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Dystonia(Moderate) | 0 participants | — |
| PF-02545920 20 mg BID | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Dystonia(Severe) | 1 participants | — |
| PF-02545920 20 mg BID | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Akathisia(Mild) | 1 participants | — |
| PF-02545920 20 mg BID | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Akathisia(Moderate) | 2 participants | — |
| PF-02545920 20 mg BID | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Akathisia(Severe) | 0 participants | — |
| PF-02545920 5 mg BID | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Akathisia(Severe) | 0 participants | — |
| PF-02545920 5 mg BID | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Dystonia(Mild) | 0 participants | 7.3 |
| PF-02545920 5 mg BID | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Akathisia(Mild) | 2 participants | — |
| PF-02545920 5 mg BID | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Akathisia(Moderate) | 1 participants | — |
| PF-02545920 5 mg BID | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Dystonia(Moderate) | 0 participants | — |
| PF-02545920 5 mg BID | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Dystonia(Severe) | 0 participants | — |
| Placebo | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Dystonia(Moderate) | 0 participants | — |
| Placebo | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Dystonia(Severe) | 0 participants | — |
| Placebo | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Akathisia(Severe) | 0 participants | — |
| Placebo | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Akathisia(Mild) | 0 participants | — |
| Placebo | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Dystonia(Mild) | 0 participants | 6.67 |
| Placebo | Severity of Adverse Events Related to Extrapyramidal Symptoms (EPS) Including Dystonia and Akathisia | Akathisia(Moderate) | 0 participants | — |