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PF-06649751

Phase 1

Idiopathic Parkinson Disease | Small molecule | Neurology |Pfizer, Inc.|Last Updated: Sep 22, 2023

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLED
Total Trials1
Total Enrollment18

FDA Designations

No designations recorded

Clinical trial landscape

PF-06649751 · 2 trials · 2 indications

Phase 1 2
NCT02373072A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of PF-06649751 in Subjects With Idiopathic Parkinson's DiseaseIdiopathic Parkinson Disease
COMPLETED18 Analytics
NCT02224664Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06649751 in Parkinson's DiseaseParkinson's Disease
COMPLETED50 Analytics
PHASE1COMPLETED
A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of PF-06649751 in Subjects With Idiopathic Parkinson's Disease
Idiopathic Parkinson DiseaseUnlock trial analytics
PHASE1COMPLETED
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06649751 in Parkinson's Disease
Parkinson's DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

Number and proportion of subjects with Adverse Events (AEs)
Day 1 through 61
Number of participants with vital signs data that meet criteria of potential clinical concern
Day 1 through 61
Number of participants with ECG data that meet criteria of potential clinical concern
Day 1 through 61
Number of participants with abnormal clinically significant laboratory measurements
Day 1 through 61
C-SSRS (suicidality assessment)
Day 1 through 61
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Baseline (Day 1) up to Day 30

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.

Number of Participants With Laboratory Test Abnormalities
Baseline up to Day 30

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.

Number of Participants With Vital Sign Abnormalities
Baseline up to Day 30

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.

Number of Participants With Electrocardiogram (ECG) Abnormalities
Baseline up to Day 30

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.

Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings
Baseline up to Day 30

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.

Number of Participants With Clinically Significant Neurological Examination Abnormality
Baseline up to Day 30

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.

Number of Participants With Categorical Scores on The Columbia Suicide Severity Rating Scale (C-SSRS)
Baseline up to Day 30

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").

Change From Baseline in Parkinson's Disease Diary For Participants With Motor Fluctuations at Day 13
Baseline, Day 13

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".

Change From Baseline in Parkinson's Disease Diary For Participants With Motor Fluctuations at Day 20
Baseline, Day 20

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".

Secondary Endpoints

MDS-UPDRS part III
Day 1, Periods 1-3
Maximum Observed Plasma Concentration (Cmax) of L-Dopa
Pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) of L-Dopa
Pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose on Day 1
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeBASIC_SCIENCE

Treatment Arms

ArmTypeDescription
Cohort 1EXPERIMENTALThree 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 2EXPERIMENTALThree 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 3EXPERIMENTALTitration of PF-06649751 up to 5 mg QD
Cohort 4EXPERIMENTALTitration of PF-06649751 up to 15 mg QD
Cohort 5EXPERIMENTALTitration of PF-06649751 up to 15 mg QDi n subjects with Levodopa-induced dyskinesias (LID)
Cohort 6EXPERIMENTALTitration of PF-0649751 up to 25 mg QD

Interventions

NameTypeDescription
PF-06649751DRUGSubjects 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 HydrochlorideDRUG300mg TID, Capsules. Optional in both Cohorts.
PlaceboDRUGSubjects completing all three treatment periods will be receiving placebo once.
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Eligibility Criteria

Age Range30 Years to 85 Years
SexALL
Healthy VolunteersNo
Study Sites8

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...

Countries:United StatesBelgium
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Frequently asked questions about PF-06649751

What is PF-06649751 used for?

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.

Who makes PF-06649751?

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.

What phase is PF-06649751 in?

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.

What clinical trials is PF-06649751 in?

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.

Is PF-06649751 the same as any other drug?

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.