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

• Register: EUCTR
• Last refreshed on: 5 June 2018
• Main ID: EUCTR2017-000128-81-DE
• Date of registration: 06/07/2017
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, New York
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 20/09/2017
• Target sample size: 198
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000128-81
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; 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

Canada, France, Germany, Spain, United States

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
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 at Screening.
2. Subjects must have successfully completed the B7601003 study through Wk 15,continue to meet all safety criteria at Screening and through Randomization visit, and must be considered compliant in the opinion of the investigator and the Sponsor.
3. No change since B7601003 study in any significant medical, rheumatologic, oncologic, neurologic, psychiatric or surgical conditions that are deemed to increase risk for participation in the extension study.
4. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures, including Parkinson’s disease diary.
5. Subjects are willing and able to continue to refrain from any medication not permitted by the protocol throughout participation in the study.
6. Subjects successfully completed study B7601003 through Wk 15, with an IP dosing gap of no more than 60 days between the 2 studies.
7. Females of non-childbearing potential and/or male subjects between the ages of 40 and 87 years, inclusive. Male subjects able to father children must agree to use 1 highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment.
Female subjects of non-childbearing potential must 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.
All other female subjects (including females with tubal ligations) will be considered to be of childbearing potential and are not eligible for participation.
8. Subjects must still be able to recognize their “wearing off” symptoms and confirm that they usually improve after their next dose of PD medication.
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 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion criteria:
Subjects with any of the following characteristics/conditions will not be included in the study:
Concomitant Medications:
1.Currently receiving an antipsychotic, metoclopramide, reserpine, or amphetamine.
2.Currently receiving moderate or strong CYP3A4 inducers or CYP3A4 inhibitors (except for topical administration).
3.Previous implantation of apomorphine pump, or surgery for intraduodenal use of Duodopa.
4.Dopamine receptor agonist medications including pramipexole, ropinirole, rotigotine and apomorphine taken within 60 days prior to Day - 1.
5.Herbal supplements taken within 28 days prior to Day -1 (Herbal supplements defined as concentrated/manufactured capsules or tablets).
6.Prohibited concomitant medications as outlined in Section 5.8, Concomitant Treatment(s) and in the Prohibited Concomitant Medication List.
Screening Assessments:
7. 12-lead ECG (average of triplicate measures) demonstrating QTcF >450 msec (>470 msec for females) or a QRS interval >120 msec at Screening.
General and Administrative:
8. Subjects who would have a gap of more than 60 days between their last IP dose in Study B7601003 and their first dose in Study B7601017.
9. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
10. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to Day-1.
11. Unwilling or unable to comply with the lifestyle requirements described in the protocol.
Medical History:
12. Emergence of severe acute or chronic medical condition, or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior, 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.
Screening Assessments:
13. Females of childbearing potential assessed at Screening; Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; fertile male subjects who are unwilling or unable to use 1 highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
14. Finding of suicidal ideation associated with actual intent and/or plan in the past year; (a “YES” answer to C-SSRS questions 4 “some intent to act without specific plan” or 5 “specific plan and intent”) not cleared by a mental health professional evaluation.
15. Screening supine blood pressure =160 mm Hg (systolic) or =95 mm Hg (diastolic), on a single measurement. If abnormal, up to 2 repeats are permitted following at least 5 minutes of rest. The screening value in that case will be the average of the 2 values closest to the normal range.
16. A decrease in systolic blood pressure (BP) of >20 mmHg or in diastolic BP of >10 mmHg measured 2 minutes after changing from a supine to standing position in the presence of symptoms of orthostasis. In the absence of symptoms of orthostasis a decrease in systolic blood pressure (BP) of >30 mmHg or in diastolic BP of >15 mmHg measured 2 minutes after changing from a supine to stan

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: LLT Classification code 10013113 Term: Disease Parkinson's System Organ Class: 100000014025

Intervention(s)

Product Code: PF-06649751 - 1mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Not yet assigned
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 Code: PF-06649751 - 5mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Not yet assigned
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

Product Code: PF-06649751 - 15mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Not yet assigned
Other descriptive name: PF-06649751
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Primary Outcome(s)

Primary end point(s): Adverse events
Physical and neurological exam findings
Clinical laboratory parameters
Vital signs
Electrocardiogram (ECG) parameters
Columbia Suicidality Severity Rating Scale (C-SSRS).
Physician Withdrawal Checklist (PWC-20).

Secondary Objective: To evaluate the long-term effect on motor symptoms of PF-06649751 administered QD in subjects with PD.
To evaluate steady state PF-06649751 concentrations following administration of PF-06649751 QD in subjects with PD.
To evaluate the long-term effect of PF-06649751 administered QD on other non-motor domains relevant in PD.
After Wk 5, the investigator will have the option to attempt a reduction of L-Dopa, after a discussion with the Sponsor, if considered appropriate:
To evaluate the reduction of L-Dopa dose while used concomitantly with daily PF-06649751 in subjects with PD.
For those subjects who participate in the Relative Bioavailability Sub-study: To evaluate the relative bioavailability of two different formulations of PF-06649751.

Timepoint(s) of evaluation of this end point: Along the study

Main Objective: To evaluate the long-term safety and tolerability of PF-06649751 administered once daily (QD) in subjects with Parkinson’s disease (PD).

Secondary Outcome(s)

Secondary end point(s): Exploratory endpoints

Daily OFF time (hours).
Daily ON time with troublesome dyskinesia (hours).
Daily ON time without troublesome dyskinesia (hours).
Movement Disorder Society-Universal Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I, II, III, IV, and total score.
Steady state plasma concentrations of PF-06649751.
Relation between PF-06649751 plasma exposures and relevant study endpoints.
EuroQol 5 Dimension (EQ-5D-5L).
Patient Global Impression-Severity (PGI-S).
For subjects who attempted to reduce L-Dopa after Wk 5:
% reduction in total daily L-Dopa dose.
Number of subjects with=25,=50%,=75% and with 100% reduction in daily L-Dopa dose.

For those subjects who participate in the Relative Bioavailability Sub-study:
Steady-state area Under the Curve from time 0 to 12 hours (AUC0-12), maximum concentration (Cmax), trough concentration (Ctrough) and time at maximum concentration (Tmax) on Visit 5 and Visit 6 in relative bioavailability (rBA) sub-study participants.

Timepoint(s) of evaluation of this end point: Along the study

Secondary ID(s)

B7601017

Source(s) of Monetary Support

Pfizer Inc.