Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
PF-06649751 · 2 trials · 2 indications
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug to the end of study (up to Day 30) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.
Criteria for laboratory abnormalities: Hemoglobin (Hgb),hematocrit, red blood cell(RBC) count: less than(\<)0.8\*lower limit of normal(LLN),mean corpuscular Hgb, mean corpuscular volume, mean corpuscular Hgb concentration:\<0.9\*LLN, greater than (\>)1.1\*upper limit of normal(ULN),platelet:\<0.5\*LLN,\>1.75\*ULN,lymphocyte,neutrophil:\<0.8\*LLN, \>1.2\*ULN, basophil, eosinophil, monocyte:\>1.2\*ULN, WBC:\<0.6\*LLN, \>1.5\*ULN;total bilirubin\>1.5\*ULN, aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase:\>3.0\*ULN,total protein,albumin:\<0.8\*LLN,\>1.2\*ULN;blood urea nitrogen,creatinine:\>1.3\*ULN, uric acid\>1.2\*ULN;sodium\<0.95\*LLN,\>1.05\*ULN,potassium,chloride,calcium,bicarbonate:\<0.9\*LLN,\>1.1\*ULN;glucose\<0.6\*LLN,\>1.5\*ULN,urine pH:\<4.5, \>8; urine: WBC, RBC greater than or equal to (\>=)20/high performance field, bacteria: \>20; urobilinogen, urine: glucose, ketone, protein, Hgb, nitrite, leukocyte esterase, bilirubin: \>=1.
Criteria for vital sign abnormality included supine pulse rate of \<40 beats per minute (bpm) or \>120 bpm, standing pulse rate of \<40 bpm or \>140 bpm, supine and standing systolic blood pressure (SBP) \<90 millimeter of mercury (mmHg), supine and standing diastolic blood pressure (DBP) \<50 mmHg, supine and standing SBP of \>=30 mmHg maximum (max.) increase from baseline (IFB) and and decrease from baseline (DFB) in same posture, supine and Standing DBP of \>=20 mmHg max. increase and decrease from baseline in same posture. Categories in which there was atleast 1 abnormality are reported in this outcome measure.
Criteria for ECG abnormalities: maximum PR interval \>=300 milliseconds (msec) and maximum increase PR interval increase from baseline (IFB): percent change (Pctchg) \>=25 percent (%) for baseline value of \>200 msec and Pctchg\>=50% for baseline value of \<=200 msec for PR interval, maximum QRS interval \>=140 msec and a maximum IFB: Pctchg\>=50%, maximum QTCF interval (Fridericia's Correction) of 450 msec to \<480 msec, 480 msec to \<500 msec or \>=500 msec and a maximum change of \<=30change\<60 or \>=60 msec from baseline.
Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.
The complete or full neurological examination included assessment of the cranial nerves; muscle strength, tone, cortical drift, abnormal movements; deep tendon reflexes; sensory exam, coordination, gait and station. Higher cortical and motor function was considered part of the complete neurological exam. Findings were considered abnormal as confirmed by a certified neurologist.
The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced any of the following 1: completed suicide, 2: suicide attempt (response of "yes" on "actual attempt"), 3: preparatory acts toward imminent suicidal behavior ("yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior"), 4: any suicidal behavior or ideation, suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent"), 7: self-injurious behavior, no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior").
According to Parkinson's disease diaries of participants "OFF" time was a time period when the medication no longer providing benefit with regard to mobility, slowness, and stiffness and participants experienced relatively poor overall function with worsening of tremor, rigidity, balance, or bradykinesia. "ON" time was a time period when medication was providing benefit with regard to mobility, slowness, and stiffness. "ON" time was classified as associated with or without troublesome dyskinesia (TD) that interfere with activities of daily living and with or without dyskinesia. "OFF" time and "ON" time with TD were generally considered to be "bad time" with regard to motor function, whereas "ON" time without dyskinesia (WD) and with non- troublesome dyskinesia (NTD) were generally considered to be "good time".
According to Parkinson's disease diaries of participants "OFF" time was a time period when the medication no longer providing benefit with regard to mobility, slowness, and stiffness and participants experienced relatively poor overall function with worsening of tremor, rigidity, balance, or bradykinesia. "ON" time was a time period when medication was providing benefit with regard to mobility, slowness, and stiffness. "ON" time was classified as associated with or without troublesome dyskinesia (TD) that interfere with activities of daily living and with or without dyskinesia. "OFF" time and "ON" time with TD were generally considered to be "bad time" with regard to motor function, whereas "ON" time without dyskinesia (WD) and with non- troublesome dyskinesia (NTD) were generally considered to be "good time".
| Arm | Type | Description |
|---|---|---|
| Cohort 1 | EXPERIMENTAL | Three single doses over three periods. For each of the three periods, subjects will be crossed-over from placebo or PF-06649751. Each PF-06649751 dose is separated by at least one week. |
| Cohort 2 | EXPERIMENTAL | Three single doses over three periods. For each of the three periods, subjects will be crossed-over from placebo or PF-06649751. Each PF-06649751 dose is separated by at least one week. |
| Cohort 3 | EXPERIMENTAL | Titration of PF-06649751 up to 5 mg QD |
| Cohort 4 | EXPERIMENTAL | Titration of PF-06649751 up to 15 mg QD |
| Cohort 5 | EXPERIMENTAL | Titration of PF-06649751 up to 15 mg QDi n subjects with Levodopa-induced dyskinesias (LID) |
| Cohort 6 | EXPERIMENTAL | Titration of PF-0649751 up to 25 mg QD |
| Name | Type | Description |
|---|---|---|
| PF-06649751 | DRUG | Subjects completing all three treatment periods will be administered two doses. Doses: 0.75mg, 1.5mg, 3mg, 6mg, 9mg. Tablets in the form of 0.25mg or 1 mg. |
| Trimethobenzamide Hydrochloride | DRUG | 300mg TID, Capsules. Optional in both Cohorts. |
| Placebo | DRUG | Subjects completing all three treatment periods will be receiving placebo once. |
Inclusion Criteria: * L-DOPA-responsiveness * Hoehn \& Yahr Stage II-III inclusive * Experiencing motor fluctuations * Stable daily dose of L-DOPA of at least 300 mg * Females on non-childbearing potential and male subjects Exclusion Criteria: * History of troublesome dyskinesias * History of sur...
PF-06649751 is an investigational small molecule being studied for Parkinson's Disease and Idiopathic Parkinson Disease. It has also been evaluated in healthy volunteers to assess safety, tolerability, and pharmacokinetics. The drug is in Phase 1 clinical development and is not yet approved by regulatory authorities.
PF-06649751 is being developed by Pfizer, Inc., which trades under the ticker symbol PFE. The company has sponsored all four clinical trials for this investigational drug, which is currently in Phase 1 development for Parkinson's Disease.
PF-06649751 is in Phase 1 clinical development. All four trials for this drug have been completed, with no active trials currently ongoing. The drug remains investigational and has not received regulatory approval for any indication.
PF-06649751 has been studied in four completed Phase 1 trials: NCT01981694 and NCT02066909 in healthy volunteers, NCT02224664 in Parkinson's Disease patients, and NCT03121664 evaluating itraconazole effects in healthy subjects. Total enrollment across these trials was 115 participants.
No alternative names for PF-06649751 have been disclosed. The drug is identified solely by its Pfizer development code across all clinical trial records. It is a distinct investigational compound being studied for Parkinson's Disease.