E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Parkinson's Disease |
Parkinson Krankheit |
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E.1.1.1 | Medical condition in easily understood language |
Gradually developing disorder of the nervous system that affects movement. |
Nach und nach Entwicklung der Störung des Nervensystems, die die Bewegung betrifft |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061536 |
E.1.2 | Term | Parkinson's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To evaluate the effect on motor symptoms of PF-06649751 administered once daily as adjunctive treatment with stable doses of L-Dopa in Parkinson’s disease. - To determine the therapeutic window for motor symptom improvement of PF-06649751 administered once daily, ie, determining a dose, or a range of doses, for adequate control of motor symptoms. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the dose-response on motor symptoms of PF-06649751 administered once daily in subjects with Parkinson’s disease. - To evaluate the safety and tolerability of PF-06649751 administered once daily in subjects with Parkinson’s disease. - To evaluate the effect of PF-06649751 administered once daily on dyskinesia in subjects with Parkinson’s disease. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Clinical diagnosis of Parkinson’s disease consistent with the United Kingdom (UK) Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria. - Parkinson’s disease Hoehn & Yahr Stage less than or equal to III while the subject is ON. - Currently responding to L-Dopa therapy. - Total duration of 2.5 hours OFF time each day, based on the OFF time diary (Hauser diary) collected over 3 consecutive days during the screening period (with fewer than 4 errors or missing entries in diary data per day) and at least 75% concordance with investigator for Screening ON/OFF time concordance testing (see Concordance Testing and OFF Time Diary Training). - Subjects must be able to recognize their “wearing off” symptoms and confirm that they usually improve after their next dose of Parkinson’s disease medication. - On a stable dose of L-Dopa of at least 400 mg total daily dose for at least 28 days prior to Day 0 (Randomization), in conjunction with a dopa-decarboxylase inhibitor (eg, L-Dopa/carbidopa or L-Dopa/benserazide) divided in at least 4 doses per day. Subjects on a stable dose of L-Dopa of at least 400 mg/day divided into 3 daily doses (TID) may be considered and authorized on a case-by-case basis if submitted as part of the screening assessment to the sponsor and/or its designee for determination if the dosing regimen is considered optimized for that particular subject. No subject on TID dosing will be considered eligible for Randomization without this additional eligibility assessment. - Willing and able to refrain from any Parkinson’s disease medication not permitted by the protocol throughout participation in the study. - Body Mass Index (BMI) of 17.5 to 35 kg/m2; and a total body weight 45 kg. - A score of 26 on the Mini Mental State Examination (MMSE). |
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E.4 | Principal exclusion criteria |
- History or clinical features consistent with an atypical Parkinsonian syndrome. - History of surgical intervention for Parkinson’s disease (pallidotomy, thalamotomy, deep brain stimulation, etc). - A score of 4 on item 4.2 Functional Impact of Dyskinesias of MDS-UPDRS Part IV (motor complications) at Screening. - Psychotic symptoms related to Parkinson’s disease requiring treatment with an antipsychotic medication within 6 months prior to Screening. - Any Parkinson’s disease-related feature or symptom that could interfere with the study conduct and results as assessed by the sponsor or Investigator. - Severe acute or chronic medical, including fever, or psychiatric condition 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. - 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), including childhood seizures, or conditions that lower seizure threshold, seizures of any etiology (including substance or drug withdrawal), or known increased risk of seizures. - A 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) that in the opinion of the investigator could interfere with study participation or poses a risk to the subject. Presence of minor depression or treated, stable depressive disorder is acceptable. - History of clinically significant alcohol or substance dependency (other than caffeine or nicotine), as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), within 1 year before Screening. - 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. - Any condition possibly affecting drug absorption, past surgery of the gastrointestinal tract (eg, gastrectomy, colectomy), except cholecystectomy. - History of vasculitis. - History of Human immunodeficiency virus (HIV) infection. - 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. - Subjects with first degree family history of unexplained sudden death, or of Long QT syndrome (LQTS). - Currently receiving an antipsychotic, metoclopramide, reserpine, or amphetamine. - Currently receiving moderate or strong CYP3A4 inducers or CYP3A4 inhibitors (except for topical administration). - Previous implantation of apomorphine pump, or surgery for intraduodenal use of Duodopa. -Dopamine receptor agonist medications including pramipexole, ropinirole, rotigotine and apomorphine must be discontinued at least 28 days prior to Day 0 (Randomization). -Herbal supplements must be discontinued at least 28 days prior to Day 0 (Randomization). |
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E.5 End points |
E.5.1 | Primary end point(s) |
(Efficacy) Change from baseline in daily OFF time (hours OFF time; based on patient reported Hauser diary) at Week 10 (Day 70; end of Period A).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
(Efficacy; Evaluated during the entire double-blind period) Placebo corrected change from baseline in: - Daily OFF time (hours). - Daily ON time with troublesome dyskinesia (hours). - Daily ON time without troublesome dyskinesia (hours). - MDS - Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III. - MDS-UPDRS Parts I, II, IV, and total score.
Safety and Tolerability - Adverse events. - Clinical laboratory parameters. - Vital signs. - 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). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy - Evaluated during the entire double-blind period Other endpoints - evaluated at the ends of Period A and B |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
Japan |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 15 |