E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013113 |
E.1.2 | Term | Disease Parkinson's |
E.1.2 | System Organ Class | 100000004852 |
|
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 assess the efficacy of different fixed doses of SYN115 for reducing the mean total hours of awake time per day spent in the OFF state in patients with Parkinson's disease (PD) treated with levodopa who have end of dose wearing off |
|
E.2.2 | Secondary objectives of the trial |
To assess the effects of SYN115 on dyskinesia; to assess the effects of SYN115 on UPDRS scores; to assess investigator and patient impressions of PD severity and change |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosis of Parkinson’s Disease, consistent with the UK Parkinson’s Disease Society Brain Bank diagnostic criteria;
Between 30 and 80 years of age at the time of study enrollment;
Hoehn & Yahr stages 2-4 when in OFF state and less than or equal to 3 in the ON state;
Must have a good response to levodopa in the opinion of the investigator and be taking at least 4 doses of a levodopa containing preparation per day;
Must have been taking levodopa continuously for at least the previous 12 months and currently experiencing end-of dose “wearing-off” fluctuations with at least 2 ½ hours of OFF per day;
Maintained on a regimen of anti Parkinson’s medications which has been stable for at least 4 weeks prior to screening;
Dopamine agonists, COMT inhibitors and MAOB inhibitor are permitted;
Achieved the following results for PD diary training, practice diary collection and baseline diary recordings- Achieved at least 75% diary concordance with an approved site trainer/rater in the 2 hour training session; Returned a valid 2-day (ie, 2 consecutive 24-hour periods) practice diary; Returned valid diary recordings for the 2 consecutive days preceding the baseline visit that indicate at least 2 ½ hours of OFF time on each of the 2 day
Contraception: - Women of childbearing potential must use an acceptable method* of contraception starting 4 weeks prior to study drug administration and for a minimum of 1 month after study completion). Otherwise, women must be post menopausal (at least 1 year absence of vaginal bleeding or spotting) as confirmed by FSH greater than or equal to 40 mIU/mL or 40 IU/L or be surgically sterile; Men with a potentially fertile partner
Able to understand and have signed an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved informed consent form to participate in this study;
Able to understand study requirements and able and willing to follow instructions, attend all required study visits, undergo all planned tests.
|
|
E.4 | Principal exclusion criteria |
Any secondary or atypical Parkinsonism (eg, drug-induced, post stroke etc.);
History of neurosurgical intervention for Parkinson’s disease;
Treatment with apomorphine in the 30 days prior to screening;
Current treatment with antipsychotics, however, quetiapine administered at doses of less than 100 mg per day is permitted if the patient has been on a stable dose for a minimum of 4 weeks prior to screening.
Treatment with any other investigational drug within 5 half-lives or 30 days prior to screening (whichever is longer) or any investigational device within 30 days;
Any other condition or clinically significant abnormal findings on the physical or neurological examination, medical and psychiatric history, at screening or at baseline that, in the opinion of the investigator, would make the subject unsuitable for the study or put the subject at additional risk or prejudice evaluation of safety and efficacy of study drug;
A score of < 26 on the Mini-Mental State Examination (MMSE) at the screening visit;
Subjects with a current episode of major depression (Subjects receiving treatment for depression with antidepressants may be enrolled if they have been on a stable dose of the anti-depressant for 4 weeks prior to randomization);
Exposure to neuroleptics (antipsychotic drugs) > 1 month within the past 5 years, or any exposure within the past year (except for quetiapine, see exclusion criterion number 4);
Women who are pregnant or lactating;
History of hepatitis (B or C) or cholangitis of any origin;
Hyperthyroidism or hypothyroidism, unless they meet all of the following conditions:
a) They have received a stable dose of thyroid medication for at least 3 months prior to Baseline visit.
b) TSH concentrations are normal or within 10% of the upper or lower limit of the normal range
c) They are clinically euthyroid
Orthostatic hypotension requiring medication;
Any out-of-range laboratory value (other than liver function tests) at screening that have not been reviewed, approved, and documented as not clinically relevant by the investigator;
Liver function tests must be within approximately 1.5X of the upper limit of normal range for AST, ALT, GGT and alkaline phosphatase;
Have a known allergy or sensitivity to SYN115 components;
Suicidal ideation on the C-SSRS of type 4 or type 5 in the past 3 months;
Finding of malignant melanoma on full body skin examination;
Subjects who are positive (give any positive answer after the gateway question) for a disorder on the modified Minnesota Impulsive Disorders Interview (mMIDI)
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to Week 12 in the 2-day average of total awake time (hours/day) spent in the OFF state for the modified Intent To Treat (mITT) analysis set. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Change from baseline to Week 12 in:
Number of hours spent in the ON state while awake based on subject-completed home diaries; Number of hours spent in the ON state without troublesome dyskinesia while awake based on subject-completed home diaries; UPDRS Part I; UPDRS Part II (Activities of Daily Living) score; UPDRS Part III score (ON), assessed approximately 2 to 3 hours after the last dose of levodopa; UPDRS total score from Part I, II and III; Clinical Global Impressions – Severity; Clinical Global Impression-Improvement; Patient Global Impression-Improvement
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
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 |
Argentina |
Canada |
Chile |
Ukraine |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |