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NCT03185481

Safety and Tolerability of PF-06649751 in Parkinson's Disease Patients With Motor Fluctuations

Terminated Phase 2 Results posted Last updated 12 April 2019
What this trial tests

Phase 2 trial testing 1 mg QD to 15 mg QD PF-06649751 in Parkinson's Disease With Motor Fluctuations in 5 participants. Terminated before completion.

Timeline
6 July 2017
Primary endpoint
24 October 2017
25 October 2017

Quick facts

Lead sponsorPfizer
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment5
Start date6 July 2017
Primary completion24 October 2017
Estimated completion25 October 2017
Sites9 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

Adults 40 to 87, any sex, with Parkinson's Disease With Motor Fluctuations. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-Emergent Adverse Events (All Causalities) Primary · Baseline to last visit after termination (up to approximately 3 months)

An adverse event (AE) is any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward were counted as treatment-emergent AE (TEAE).

GroupValue95% CI
PF-06649751 15 mg3
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) Primary · Baseline to last visit after termination (up to approximately 3 months)

An adverse event (AE) is any untoward medical occurrence in a study participant administered a product or medical device. Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward were counted as treatment-emergent AE (TEAE).

GroupValue95% CI
PF-06649751 15 mg2
Number of Participants With Clinically Significant Findings in Physical Examination Primary · Baseline to last visit after termination (up to approximately 3 months)

A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal and musculoskeletal systems. The clinical significance was determined by the investigator.

GroupValue95% CI
PF-06649751 15 mg0
Number of Participants With Clinically Significant Findings in Neurological Examination Primary · Baseline to last visit after termination (up to approximately 3 months)

The full neurological examination included assessment of the visual fields and of the right and left optic fundus; cranial nerves; mental state; muscle strength and tone, abnormal movements; deep tendon reflexes; sensory exam, coordination, gait and station. Higher cortical and motor function was considered part of the complete neurological exam. The brief neurological exam included observation for cerebellar (intention) tremor and for non cerebellar tremors (eg, resting or positional), finger to nose, heel to shin, Romberg, gait and tandem walking, positional and gaze evoked nystagmus. The cl

GroupValue95% CI
PF-06649751 15 mg0
Number of Participants With Abnormalities in Laboratory Test (Without Regard to Baseline Abnormality) Primary · Baseline to last visit after termination(up to approximately 3 months)

Laboratory tests included hematology(hemoglobin,hematocrit,red and white blood cell count,mean corpuscular volume,mean corpuscular hemoglobin,mean corpuscular hemoglobin concentration,platelet count,neutrophils,eosinophils,monocytes, basophils,lymphocytes), chemistry(blood urea nitrogen/urea and creatinine,fasting glucose, calcium,sodium,potassium, chloride,total carbon dioxide,aspartate and alanine aminotransferase,total bilirubin,alkaline phosphatase,uric acid,albumin,total protein),urinalysis(pH,qualitative glucose protein,blood,ketones,nitrites,leukocyte esterase,urobilinogen,urine bilirub

GroupValue95% CI
PF-06649751 15 mg1
Number of Participants With Vital Signs Data Meeting Pre-defined Criteria Primary · Baseline to last visit after termination (up to approximately 3 months)

Number of participants with vital signs findings meeting the following criteria is presented:(1) standing DBP increase from baseline\>= 20 mm Hg; (2) standing SBP increase from baseline\>= 30 mm Hg; (3) supine DBP increase from baseline \>=20 mm Hg; (4) supine SBP increase from baseline \>=30 mm Hg; (5)standing DBP decrease from baseline\>= 20 mm Hg; (6) standing SBP decrease from baseline\>= 30 mm Hg; (7) supine DBP decrease from baseline \>=20 mm Hg; (8) supine SBP decrease from baseline \>=30 mm Hg.

Standing DBP increase from baseline >= 20 mm Hg
GroupValue95% CI
PF-06649751 15 mg0
Standing SBP increase from baseline >= 30 mm Hg
GroupValue95% CI
PF-06649751 15 mg1
Supine DBP increase from baseline >= 20 mm Hg
GroupValue95% CI
PF-06649751 15 mg0
Supine SBP increase from baseline >= 30 mm Hg
GroupValue95% CI
PF-06649751 15 mg2
Standing DBP decrease from baseline >= 20 mm Hg
GroupValue95% CI
PF-06649751 15 mg0
Standing SBP decrease from baseline >= 30 mm Hg
GroupValue95% CI
PF-06649751 15 mg0
Supine DBP decrease from baseline >= 20 mm Hg
GroupValue95% CI
PF-06649751 15 mg0
Supine SBP decrease from baseline >= 30 mm Hg
GroupValue95% CI
PF-06649751 15 mg0
Number of Participants With Vital Signs Data of Orthostatic Hypotension Meeting Pre-defined Criteria Primary · Baseline to last visit after termination (up to approximately 3 months)

Orthostatic hypotension was defined as a decrease of \>=20 mmHg for systolic blood pressure (SBP) or \>=10 mmHg for diastolic blood pressure (DBP) 2 minutes after standing from a supine position.

DBP postural difference>=10 mm Hg(Supine-Standing)
GroupValue95% CI
PF-06649751 15 mg3
SBP postural difference>=20 mm Hg(Supine-Standing)
GroupValue95% CI
PF-06649751 15 mg4
Number of Participants With Electrocardiogram Data Meeting Pre-defined Criteria Primary · Baseline to last visit after termination (up to approximately 3 months)

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), QRS duration (time from Q wave to the end of S wave, corresponding to ventricle depolarization), QT interval (time from the beginning of Q wave to the end of T wave) and QTcF interval ( QT interval corresponding to electrical systole corrected for heart rate using Fridericia's formula) are summarized. Number of participants with ECG findings meeting the following criteria is presented: (1) PR interval \>=300 msec; (2) QRS durati

PR Interval (aggregate) >= 300 msec
GroupValue95% CI
PF-06649751 15 mg0
QRS Duration (aggregate) >= 140 msec
GroupValue95% CI
PF-06649751 15 mg0
QT Interval (aggregate) >= 500 msec
GroupValue95% CI
PF-06649751 15 mg0
QTcF Interval (aggregate) >= 450 msec, <480msec
GroupValue95% CI
PF-06649751 15 mg0
QTcF Interval (aggregate) >= 480 msec, <500msec
GroupValue95% CI
PF-06649751 15 mg0
QTcF Interval (aggregate) >= 500 msec
GroupValue95% CI
PF-06649751 15 mg0
Number of Participants With Worsening Suicidality and New Onset Suicidality Primary · Baseline to last visit after termination (up to approximately 3 months)

The Columbia Suicide Severity Rating Scale (C-SSRS) is an interview based rating scale to systematically assess suicidal ideation and suicidal behavior. At each suicidality assessment, participants felt to have significant suicidal ideation with actual plan and intent or suicidal behavior, must be evaluated by a clinician/mental health professional (MHP) skilled in the evaluation of suicidality in the participants by virtue of training or experience who determined if it is safe for the participants to participate/continue in the trial. The denominator used in the percentages was the number of

New Onset
GroupValue95% CI
PF-06649751 15 mg0
Worsening
GroupValue95% CI
PF-06649751 15 mg0
Number of Participants With Benzodiazepine Discontinuation Symptoms Based on Physician Withdrawal Checklist (PWC-20) Primary · At last visit

The PWC-20 is a physician-completed, 20-item reliable and sensitive instrument for the assessment of benzodiazepine discontinuation symptoms, including anxiety and nervous, depersonalization and derealization, diarrhea, diaphoresis, difficulty concentrating and remembering, dizziness-lightheadedness, depression, fatigue, lethargy and lack of energy, headaches, increased acuity for sound, smell, touch, or pain, insomnia, irritability, loss of appetite, muscle aches or stiffness, nausea-vomiting paresthesias, poor coordination, restlessness and agitation, tremor-tremulousness, and weakness. Summ

Anxiety, Nervousness
GroupValue95% CI
PF-06649751 15 mg3
PF-06649751 15 mg1
PF-06649751 15 mg0
PF-06649751 15 mg0
Difficult Concentrating, Remembering
GroupValue95% CI
PF-06649751 15 mg3
PF-06649751 15 mg1
PF-06649751 15 mg0
PF-06649751 15 mg0
Dysphoric Mood, Depression
GroupValue95% CI
PF-06649751 15 mg3
PF-06649751 15 mg1
PF-06649751 15 mg0
PF-06649751 15 mg0
Fatigue, Lethargy, Lack of Energy
GroupValue95% CI
PF-06649751 15 mg2
PF-06649751 15 mg1
PF-06649751 15 mg1
PF-06649751 15 mg0
Insomnia
GroupValue95% CI
PF-06649751 15 mg2
PF-06649751 15 mg1
PF-06649751 15 mg1
PF-06649751 15 mg0
Irritability
GroupValue95% CI
PF-06649751 15 mg3
PF-06649751 15 mg0
PF-06649751 15 mg1
PF-06649751 15 mg0
Muscle Aches or Stiffness
GroupValue95% CI
PF-06649751 15 mg3
PF-06649751 15 mg0
PF-06649751 15 mg1
PF-06649751 15 mg0
Poor Coordination
GroupValue95% CI
PF-06649751 15 mg2
PF-06649751 15 mg1
PF-06649751 15 mg1
PF-06649751 15 mg0
Change From Baseline for Hauser Participant Diary Data in Daily OFF Time Secondary · Baseline, Day 21 and Day 35

Available diaries are designed to record participant motor state for half hour intervals. These diaries are a way for participant to assess their own health status without clinician bias or interpretation. In participant diaries, "OFF" time is defined as a period when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness. During this period, Parkinson's Disease (PD) participants experience relatively poor overall function with worsening of tremor, rigidity, balance, or bradykinesia.

Baseline
GroupValue95% CI
PF-06649751 15 mg3.25± NA
Day 21
GroupValue95% CI
PF-06649751 15 mg0.00± NA
Day 35
GroupValue95% CI
PF-06649751 15 mg-0.42± NA
Change From Baseline for Hauser Participant Diary Data in Daily ON Time With Troublesome Dyskinesia Secondary · Baseline, Day 21 and Day 35

Available diaries are designed to record participant motor state for half hour intervals. These diaries are a way for participants to assess their own health status without clinician bias or interpretation. "ON" time is defined as the time when medication is providing benefit with regard to mobility, slowness, and stiffness. "ON" time can be classified as associated with or without troublesome dyskinesia that interfere with activities of daily living.It has been demonstrated that "ON" time with troublesome dyskinesia are generally considered by participants to be "bad time" with regard to moto

Baseline
GroupValue95% CI
PF-06649751 15 mg0.00± NA
Day 21
GroupValue95% CI
PF-06649751 15 mg0.00± NA
Day 35
GroupValue95% CI
PF-06649751 15 mg0.00± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline to last visit after termination (up to approximately 3 months). Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PF-06649751 15 mg
Serious: 1/5 (20%)
Deaths: 0/5

Serious adverse events (1 terms)

ReactionSystemPF-06649751 15 mg
Hip FractureInjury, poisoning and procedural complications
Other adverse events (3 terms — click to expand)

ReactionSystemPF-06649751 15 mg
HeadacheNervous system disorders
Orthostatic hypotentionVascular disorders
FallInjury, poisoning and procedural complications

Most-reported serious reactions: Hip Fracture.

Data from ClinicalTrials.gov NCT03185481 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the long term safety and tolerability of PF-06649751 in Parkinson's disease patients who experience motor-fluctuations.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Recent advances in dopaminergic strategies for the treatment of Parkinson's disease.
    Mao Q, Qin WZ, Zhang A, Ye N. · · 2020 · cited 63× · PMID 32112042 · DOI 10.1038/s41401-020-0365-y
  2. Phase 1 Parkinson's Disease Studies Show the Dopamine D1/D5 Agonist PF-06649751 is Safe and Well Tolerated.
    Sohur US, Gray DL, Duvvuri S, Zhang Y, et al · · 2018 · cited 36× · PMID 30361858 · DOI 10.1007/s40120-018-0114-z

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