A 15-WEEK CLINICAL STUDY TO DETERMINE THE EFFECTIVENESS, SAFETY AND TOLERABILITY OF PF-06649751 IN PATIENTS WITH EARLY PARKINSON’S DISEASE

• Register: EUCTR
• Last refreshed on: 1 October 2018
• Main ID: EUCTR2016-001575-71-DE
• Date of registration: 26/09/2016
• Prospective Registration: Yes
• Primary sponsor: Pfizer, Inc.
• Public title: A 15-WEEK CLINICAL STUDY TO DETERMINE THE EFFECTIVENESS, SAFETY AND TOLERABILITY OF PF-06649751 IN PATIENTS WITH EARLY PARKINSON’S DISEASE
• Scientific title: A 15 WEEK, PHASE 2, DOUBLE BLIND, RANDOMIZED, PLACEBO CONTROLLED, FLEXIBLE DOSE STUDY TO INVESTIGATE THE EFFICACY, SAFETY AND TOLERABILITY OF PF-06649751 IN SUBJECTS WITH EARLY STAGE PARKINSON’S DISEASE
• Date of first enrolment: 23/12/2016
• Target sample size: 88
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001575-71
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Israel, Spain, United States

Contacts

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc.

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Females of non childbearing potential and/or male subjects between the ages of 45 and 80 years, inclusive.
4. Male subjects able to father children must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment.
5. Female subjects of non childbearing potential (ie, meet at least 1 of the following criteria):
- Have undergone a documented hysterectomy and/or bilateral oophorectomy;
- Have medically confirmed ovarian failure; or
- Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level confirming the post menopausal state.
6. Clinical diagnosis of Parkinson’s disease consistent with the United Kingdom (UK) Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria (Appendix 4).
7. Parkinson’s Disease Hoehn & Yahr Stage I III inclusive.
8. Parkinson’s disease subjects deemed appropriate for treatment of motor symptoms with a MDS UPDRS Part III score >=10.
9. Treatment naïve or history of prior incidental treatment with dopaminergic agents (including L Dopa and dopamine receptor agonist medications) for no more than 28 days and not within at least 7 days prior to Visit 1 (Randomization) as outlined in Section 5.8, Concomitant Treatment(s), and Appendix 2 in the protocol.
10. Willing and able to refrain from any Parkinson’s disease medication not permitted by the protocol (including dopaminergic agents) throughout participation in the study as outlined in Appendix 2 in the protocol.
11. A score of >=26 on the Mini Mental State Examination (MMSE).
12. Body Mass Index (BMI) of 17.5 to 35 kg/m2; and a total body weight >= 45 kg.


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 53
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35

Exclusion criteria:
1. History or clinical features consistent with an atypical Parkinsonian syndrome (including but not limited to Progressive Supranuclear Palsy, Multiple System Atrophy, Cortico Basal Degeneration, etc).
2. Any Parkinson’s disease related feature or symptom that could interfere with the study conduct and results as assessed by the sponsor or Investigator.
3. Presence of acute or chronic clinically significant medical, including fever, or psychiatric condition or cognitive impairment or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
4. Presence or history of brain tumor, past history of hospitalization for head trauma with loss of consciousness, epilepsy (as defined by the International League Against Epilepsy)E31, including childhood seizures, or conditions that lower seizure threshold, seizures of any etiology (including substance or drug withdrawal), or known increased risk of seizures.
5. Any significant AXIS I psychiatric disease as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition Revised (DSM IV TR, American Psychiatric Association, 2000) including subjects with clinically significant depression (PHQ 8 total score >=15) (refer to Section 7.1.6 of the protocol, Depression Assessment (PHQ 8). Presence of minor depression or treated, stable depressive disorder is acceptable.
6. Subjects who have made a suicide attempt within the last 5 years. Subjects who, in the investigator’s judgment, pose a significant suicide risk. Subjects who have suicidal ideation associated with actual intent and a method or plan in the past 6 months (ie, “Yes” answers on items 4 or 5 of the C-SSRS; refer to Section 7.3 Assessment of Suicidal Ideation and Behavior (C-SSRS).
7. History of clinically significant alcohol or substance dependency (other than caffeine or nicotine), as defined in DSM IV TR, within 1 year before Screening.
8. In the opinion of the investigator (or caregiver, as applicable), has signs/symptoms suggestive of clinically significant cognitive impairment that would interfere with the ability to comply with study procedures.
9. Any condition possibly affecting drug absorption, past surgery of the gastrointestinal tract (eg, gastrectomy, colectomy), except cholecystectomy.
10. History of vasculitis.
11. History of Human Immunodeficiency Virus (HIV) infection.
12. History of malignancy other than:
• Non-metastatic basal or squamous cell carcinoma of the skin or carcinoma in situ that was surgically removed in total >1 year before screening and has not recurred.
• Other type of malignancy which has been in remission 5 years or more before screening and has not recurred.
13. Subjects with first degree family history of unexplained sudden death, or of Long QT syndrome (LQTS).
14. Within 1 year of Screening or between Screening and Visit 1 (Randomization), any of the following: myocardial infarction; moderate or severe congestive heart failure, NYHA class III or IV; hospitalization for, or symptoms of, unstable angina; syncope due to orthostatic hypotension or unexplained syncope; known significant structural heart disease (eg, significant valvular disease, hypertrophic cardiomyopathy); or hospitalization for arrhythmia.
15. Currently receiving moderate or str

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Parkinson's Disease
MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: PF-06649751
Product Code: PF-06649751
Pharmaceutical Form: Tablet
INN or Proposed INN: PF-06649751
Current Sponsor code: PF-06649751
Other descriptive name: PF-06649751
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: PF-06649751
Product Code: PF-06649751
Pharmaceutical Form: Tablet
INN or Proposed INN: PF-06649751
Current Sponsor code: PF-06649751
Other descriptive name: PF-06649751
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: PF-06649751
Product Code: PF-06649751
Pharmaceutical Form: Tablet
INN or Proposed INN: PF-06649751
Current Sponsor code: PF-06649751
Other descriptive name: PF-06649751
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: - To evaluate the safety and tolerability of PF 06649751 administered once daily in subjects with early stage Parkinson’s disease.
- To evaluate the effect of PF 06649751 administered once daily on other domains relevant in early Parkinson’s disease (eg, depression, daytime sleepiness, and cognition).
- To characterize steady state plasma concentrations of PF 06649751.
- To explore the relationship between PF 06649751 plasma exposures and relevant study endpoints.
- Pooled or exploratory analyses, if conducted, utilizing the biobanked exploratory genomic and biomarker samples across PF 06649751 studies or across multiple programs will be documented in a separate protocol and/or statistical analysis plan.

Primary end point(s): (Efficacy) Change from baseline in the Modified Unified Parkinson’s Disease Rating Scale (MDS UPDRS) Score Part III

Timepoint(s) of evaluation of this end point: Week 15

Main Objective: - To evaluate the effect of PF 06649751 administered once daily on motor symptoms in subjects with early stage Parkinson’s disease.

Secondary Outcome(s)

Secondary end point(s): (Safety and Tolerability)
- Adverse events.
- Clinical laboratory parameters.
- Vital signs.
- Electrocardiogram (ECG) parameters.
- Columbia Suicide Severity Rating Scale (C-SSRS).
- Questionnaire for Impulsive Compulsive Disorders in Parkinson’s Disease – Rating Scale (QUIP RS).
- Physician Withdrawal Checklist (PWC 20).

(Exploratory endpoints)
- Beck Depression Inventory – II (BDI II).
- Epworth Sleepiness Scale (ESS).
- Patient Global Impression Severity (PGI S).
- Patient Global Impression – Improvement (PGI I).
- Parkinson’s Disease Questionnaire (PDQ 39).
- EuroQol 5 Dimension (EQ 5D 5L).
- Oral Symbol Digit Modality Test.
- Modified Clinical Global Impression-Severity (MCGI S).
- Modified Clinical Global Impression-Improvement (MCGI I).
- MDS – UPDRS Part I.
- MDS – UPDRS Part II.
- MDS – UPDRS Parts II + III.
- MDS – UPDRS Parts I + II + III.
- MDS – UPDRS Total Score (Parts I + II + III + IV).
- Average plasma PF-06649751 concentrations
- Exploratory exposure response relationship with relevant endpoints.
- Serum Prolactin level at Visit 14.
- Banked biospecimens for possible follow up analysis.

Timepoint(s) of evaluation of this end point: Safety and tolerability endpoints are assessed throughout the course of the study

Exploratory endpoints:
- Change from baseline at Weeks 10 and 15: BDI II, ESS, PGI S, PGI I, PDQ 39, EQ 5D 5L, Symbol Digit Modality Test, MCGI S, MCGI I, MDS - UPDRS Part I and Part II, Parts II+III, Parts I+II+III, Total Score - Parts I+II+III+IV
- PF-06649751 plasma concentrations - Visit 4, 6, 10, 12 and 14
- Serum prolaction level

Secondary ID(s)

B7601011

Source(s) of Monetary Support

Pfizer, Inc