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Parkinson's Disease With Motor FluctuationsPhase 2NCT03185481

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

A Phase 2 study testing 1 mg QD to 15 mg QD PF-06649751, 3 mg QD to 15 mg QD PF-06649751 and 7 mg QD to 15 mg QD PF-06649751 in people with Parkinson's Disease With Motor Fluctuations, run by Pfizer at 9 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 40 to 87 years
What is being tested?
1 mg QD to 15 mg QD PF-06649751, 3 mg QD to 15 mg QD PF-06649751 and 7 mg QD to 15 mg QD PF-06649751
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
9 sitesUnited States
Study dates
6 Jul 2017to 25 Oct 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 87 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Having successfully completed parent study B7601003.
  • Clinical diagnosis of Parkinson's disease.
  • Able to refrain from any Parkinson's disease medication not permitted by the protocol.

Who cannot join

  • Female of childbearing potential.
  • Severe acute or chronic medical or psychiatric condition or laboratory abnormality.
  • Participation in other studies involving investigational drug(s), or treatment with any investigational drug within 30 days.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Atlanta Center for Medical Research

    Atlanta, Georgia, 30331

  • Parkinson's Disease and Movement Disorders Center of Boca Raton

    Boca Raton, Florida, 33486

  • Associated Neurologists of Southern CT, PC

    Fairfield, Connecticut, 06824

  • Booth Gardner Parkinson's Care Center

    Kirkland, Washington, 98034

  • Pharmaceutical Research Associates, Inc.

    Marlton, New Jersey, 08053

  • Hoag Memorial Hospital Presbyterian

    Newport Beach, California, 92663

  • University of Toledo, Gardner-McMaster Parkinson Center

    Toledo, Ohio, 43614

  • University of Toledo, Investigational Drug Services

    Toledo, Ohio, 43614

  • The Movement Disorder Clinic of Oklahoma

    Tulsa, Oklahoma, 74136

Other trials in United States

About this study

Official title: A PHASE 2, OPEN LABEL EXTENSION STUDY TO INVESTIGATE THE LONG TERM SAFETY AND TOLERABILITY OF PF-06649751 IN SUBJECTS WITH MOTOR FLUCTUATIONS DUE TO PARKINSON'S DISEASE

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.

Read the detailed description

This is an open label study evaluating the long term safety and tolerability of PF-06649751 in Parkinson's disease patients who experience motor-fluctuations. Subjects who completed Ph2 study B7601003 will be randomized to one of 4 treatment groups (15 mg QD, 7 mg QD, 3 mg QD, or 1 mg QD group) depending on the treatment received in B7601003 and titrated up to 15 mg QD over a 3 week period, as appropriate. All subjects who were blindly down-titrated during the B7601003 study will remain at/or be titrated to 7 mg QD only and remain at that dose for the rest of the B7601017 study in order to protect the blind for the prior study. Subjects who successfully titrate to 15 mg QD will enter the Adjustment Period at that dose.

Subjects who cannot tolerate 15 mg QD at any time during the study will be allowed to down-titrate to 7 mg QD (but not lower) and will stay at that dose for the rest of the study.

Subjects who cannot remain at a stable dose (7 mg or 15 mg QD) will be discontinued.

Being tested
1 mg QD to 15 mg QD PF-06649751, 3 mg QD to 15 mg QD PF-06649751, 7 mg QD to 15 mg QD PF-06649751, 15 mg QD PF-06649751, 1 mg QD to 7 mg QD PF-06649751 (if de-escalated in parent study)
Keywords
Parkinson's Disease, Motor Fluctuations, D1 partial agonist
Medical subject headings
Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 1 mg QD to 15 mg QD PF-06649751Drug

    Up titration from 1 mg QD to 15 mg QD PF-06649751

  • 3 mg QD to 15 mg QD PF-06649751Drug

    Up titration from 3 mg QD to 15 mg QD PF-06649751

  • 7 mg QD to 15 mg QD PF-06649751Drug

    Up titration from 7 mg QD to 15 mg QD PF-06649751

  • 15 mg QD PF-06649751Drug

    15 mg QD PF-06649751 remaining at 15 mg QD PF-06649751

  • 1 mg QD to 7 mg QD PF-06649751 (if de-escalated in parent study)Drug

    Up titration from 1 mg QD to 7 mg QD PF-06649751 for subject at 1 mg QD who were blindly de-escalated in the parent study

  • 3 mg QD to 7 mg QD PF-06649751 (de-escalated in parent study)Drug

    Up titration from 3 mg QD to 7 mg QD PF-06649751 for 3 mg QD subjects who were blindly de-escalated in parent study

  • 7 mg QD to 7 mg QD PF-06649751 (de-escalated in parent study)Drug

    7 mg QD to remain at 7 mg QD PF-06649751 for subjects who were blindly de-escalated in parent study

  • 15 mg QD de-escalated to 7 mg QD PF-06649751 in parent study remain at 7 mg QDDrug

    7mg QD PF-06649751 for subjects assigned to 15 mg QD who were blindly de-escalated to 7 mg QD PF-06649751 in parent study

Study groups in NCT03185481
Study groupRoleWhat they receive
1 mg QD to 15 mg QD PF-06649751ExperimentalUp titration from 1 mg QD to 15 mg QD PF-06649751
Receives: Drug: 1 mg QD to 15 mg QD PF-06649751
3 mg QD to 15 mg QD PF-06649751ExperimentalUp titration from 3 mg QD to 15 mg QD PF-06649751
Receives: Drug: 3 mg QD to 15 mg QD PF-06649751
7 mg QD to 15 mg QD PF-06649751ExperimentalUp titration from 7 mg QD to 15 mg QD PF-06649751
Receives: Drug: 7 mg QD to 15 mg QD PF-06649751
15 mg QD PF-06649751Experimental15 mg QD PF-06649751 remains at 15 mg QD PF-06649751
Receives: Drug: 15 mg QD PF-06649751
1 mg to 7 mg QD PF-06649751ExperimentalUp titration from 1 to 7 mg QD PF-06649751 if de-escalated in parent study
Receives: Drug: 1 mg QD to 7 mg QD PF-06649751 (if de-escalated in parent study)
3 mg QD to 7 mg QD PF-06649751ExperimentalUp titration from 3 to 7 mg QD PF-06649751 if de-escalated in parent study
Receives: Drug: 3 mg QD to 7 mg QD PF-06649751 (de-escalated in parent study)
7 mg QD to 7 mg QD PF-06649751Experimental7 mg QD remains at 7 mg QD PF-06649751 if de-escalated in parent study
Receives: Drug: 7 mg QD to 7 mg QD PF-06649751 (de-escalated in parent study)
15 mg to 7 mg QD PF-06649751Experimental15 mg QD de-escalated to 7 mg QD in parent study B7601003 remain at 15 mg QD PF-06649751
Receives: Drug: 15 mg QD de-escalated to 7 mg QD PF-06649751 in parent study remain at 7 mg QD

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Treatment-Emergent Adverse Events (All Causalities)

    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).

    Measured: Baseline to last visit after termination (up to approximately 3 months)

  2. Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)

    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).

    Measured: Baseline to last visit after termination (up to approximately 3 months)

  3. Number of Participants With Clinically Significant Findings in Physical Examination

    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.

    Measured: Baseline to last visit after termination (up to approximately 3 months)

  4. Number of Participants With Clinically Significant Findings in Neurological Examination

    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 clinical significance was determined by the investigator.

    Measured: Baseline to last visit after termination (up to approximately 3 months)

  5. Number of Participants With Abnormalities in Laboratory Test (Without Regard to Baseline Abnormality)

    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 bilirubin,microscopy,specific gravity,urine creatinine),other tests(urine drug screen,follicle stimulating hormone,anti neutrophil cytoplasmic antibody panel,qualitative antinuclear antibody,fibrinogen,C reactive protein,erythrocyte sedimentation rate,C3, C4, CH50/CH100,rheumatoid factor,immunoglobulin panel,if anti- neutrophil cytoplasmic antibody positive:proteinase 3 Ab,myeloperoxidase Ab tests).

    Measured: Baseline to last visit after termination(up to approximately 3 months)

  6. Number of Participants With Vital Signs Data Meeting Pre-defined Criteria

    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.

    Measured: Baseline to last visit after termination (up to approximately 3 months)

  7. Number of Participants With Vital Signs Data of Orthostatic Hypotension Meeting Pre-defined Criteria

    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.

    Measured: Baseline to last visit after termination (up to approximately 3 months)

  8. Number of Participants With Electrocardiogram Data Meeting Pre-defined Criteria

    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 duration >=140 msec; (3) QT interval >= 500; (4) QTcF interval: 450 to <480 msec; (5) QTcF interval: 480 to <500 msec; (6) QTcF interval >=500 msec.

    Measured: Baseline to last visit after termination (up to approximately 3 months)

  9. Number of Participants With Worsening Suicidality and New Onset Suicidality

    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 participants assessed for suicidality or worsening, the denominator included the subset of participants who had any level of suicidality reported at baseline. For new onset, the denominator included the subset of participants with no suicidality reported at baseline.

    Measured: Baseline to last visit after termination (up to approximately 3 months)

  10. Number of Participants With Benzodiazepine Discontinuation Symptoms Based on Physician Withdrawal Checklist (PWC-20)

    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. Summaries of the count of participants experiencing symptoms and severity listed in the PWC-20 were provided.

    Measured: At last visit

Secondary outcomes (4)

  1. Change From Baseline for Hauser Participant Diary Data in Daily OFF Time

    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.

    Measured: Baseline, Day 21 and Day 35

  2. Change From Baseline for Hauser Participant Diary Data in Daily ON Time With Troublesome Dyskinesia

    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 motor function.

    Measured: Baseline, Day 21 and Day 35

  3. Change From Baseline for Hauser Participant Diary Data in Daily ON Time Without Troublesome Dyskinesia

    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. "ON" time without dyskinesia and on time with non troublesome dyskinesia are generally considered to be "good time".

    Measured: Baseline, Day 21 and Day 35

  4. Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, III, IV, and Total Score

    The total MDS-UPDRS score developed by the Movement Disorder Society is the most common method of evaluating the severity of Parkinson's Disease (PD). Part I assesses non motor experiences of daily living(range 0-52).Part II assesses motor experiences of daily living(0-52). Part III assesses the motor signs of PD.Part IV assesses motor complications, dyskinesias, and motor fluctuations(0-24).Total Score:The sum of Parts I, II, III, and IV.Each question is anchored with five responses:0=normal, 1=slight, 2=mild, 3= moderate, 4=severe.Higher part and total scores indicate more severe signs of PD.There are four subscales in Part III:the tremor subscale(range 0-36),the rigidity subscale(0-20),the bradykinesia subscale(0-36),the postural instability and gait disorder (PIGD) subscale(0-12).

    Measured: Baseline to last visit after termination (up to approximately 3 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2017
  2. Study start6 Jul 2017
  3. Primary completion24 Oct 2017
  4. Study completion25 Oct 2017

Why it stopped: Terminated 25Sep17 due to parent study insufficient efficacy. Not due to safety

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Depending on the actual treatment the subject received in B7601003, subjects will be randomized to one of 4 treatment groups (15 mg QD, 7 mg QD, 3 mg QD, or 1 mg QD group) and titrated up to 15 mg QD over a 3 week period, as appropriate. All subjects who were blindly down-titrated during the parent study (B7601003) will remain at/or be titrated to 7 mg QD only and remain at that dose for the rest of the B7601017 study in order to protect the blind for the parent study. Subjects who successfully titrate to 15 mg QD will enter the Adjustment Period at that dose. Subjects who cannot tolerate 15 mg QD at any time during the study will be allowed to down-titrate to 7 mg QD (but not lower) and will stay at that dose for the rest of the study. Subjects who cannot remain at a stable dose (7 mg or 15 mg QD) will be discontinued.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03185481
Sponsor's protocol ID
B7601017
Other IDs
2017-000128-81, 2017
Status last verified
Apr 2019
First submitted
9 Jun 2017
Last updated
12 Apr 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 1 mg QD to 15 mg QD PF-06649751, 3 mg QD to 15 mg QD PF-06649751 and 7 mg QD to 15 mg QD PF-06649751 in people with Parkinson's Disease With Motor Fluctuations, run by Pfizer at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-Emergent Adverse Events (All Causalities) (time frame: Baseline to last visit after termination (up to approximately 3 months)). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03185481.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2019.

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