E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with Parkinson’s Disease with motor fluctuations |
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E.1.1.1 | Medical condition in easily understood language |
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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 determine the effect of two dosing regimens of ND0612 on daily “OFF” time using subject-completed home diary assessments of motor function. |
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E.2.2 | Secondary objectives of the trial |
To determine the effect of two dosing regimens of ND0612 on daily “ON” time without troublesome dyskinesia (defined as the sum of "ON" time without dyskinesia and “ON” time with non-troublesome dyskinesia) using subject-completed home diary assessments of motor function. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- Pharmacokinetics Sub-study: Protocol ND0612L-007 - PK Sub-study version 1.0 dated 10 July 2017. PK Sub-study objective:To assess the PK of LD, CD, and the LD metabolite 3-OMD in 2 dosing regimens of ND0612 (high-dose and low-dose administration) together with oral adjunct therapy in a sub-study of Study ND0612L-007 performed in a sub-group of subjects at selected sites. Concentration measurements will also be performed for selected subjects receiving placebo.
- Pharmacogenetics Sub-study: Protocol ND0612L-007 - PGx Sub-study version 1.0 dated 03 July 2017 PGx Sub-study objective: To analyze the correlation of potential genetic variations and clinical treatment responses to study drug (e.g. efficacy, pharmacokinetics, tolerability and safety features). |
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E.3 | Principal inclusion criteria |
1. Male and female PD subjects of any race aged at least 30 years 2. PD diagnosis consistent with the UK Brain Bank Criteria. 3. Modified Hoehn & Yahr scale in “ON” state ≤3 4. Subjects must experience motor fluctuations and experience an average of at least 2 hours daily in the “OFF” state 5. Subject treatment is stable with at least 4 doses/day of LD/DDI (or at least 3 doses/day of Rytary) and according to the Investigator judgment, motor fluctuations cannot be further improved by adjusting oral LD medications. 6. Subjects must be on stable doses of all their anti-PD medications for at least 28 days before Baseline (Day 1). 7. Subject and/or study partner must demonstrate ability to keep accurate diary entries of PD symptoms (“ON-OFF” diaries) with at least 75% concordance with the study rater by the end of the diary training session at the end of the screening period. 8. Mini Mental State Examination (MMSE) score > 24. 9. Female subjects must be surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation), postmenopausal (defined as cessation of menses for at least 1 year), or willing to practice a highly effective method of contraception.
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E.4 | Principal exclusion criteria |
1. Atypical or secondary parkinsonism. 2. Acute psychosis or troublesome hallucinations in past 6 months. 3. Subjects with a clinically significant or unstable medical, surgical, psychiatric condition or laboratory abnormalities which, in the opinion of the Investigator or the EAC, represents a safety risk, makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study. 4. Clinically significant ECG abnormalities. 5. Renal or liver dysfunction that may alter drug metabolism including Screening visit serum levels of creatinine >1.5 mg/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2x upper limit of normal (ULN), total bilirubin >2.5 mg/dL. 6. Positive serum serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) at the Screening visit 7. Any malignancy in the 5 years prior to randomization excluding basal cell carcinoma of the skin or cervical carcinoma in situ that have been successfully treated 8. Use of prohibited medications as per protocol 9. Subjects who have previously undergone treatment for PD with a neurosurgical intervention (e.g., pallidotomy, thalamotomy, transplantation, deep brain stimulation procedures), Duodopa/Duopa, or continuous dopaminergic or apomorphine infusion. 10. Subjects with skin lesions that might interfere with a subcutaneous treatment regimen. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change from Baseline to Week 16 in the mean percentage of “OFF” time during waking hours, based on subject's home diary assessments on 3 consecutive days before the visit. The “OFF” time will also be presented as hours normalized to 16 waking hours. |
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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) |
The key secondary efficacy endpoint is the change from Baseline to Week 16 in the mean percentage of “ON” time without troublesome dyskinesia during waking hours, based on subject's home diary assessments on the 3 consecutive days before the visit. "ON" time without troublesome dyskinesia is defined as the sum of "ON" time without dyskinesia and “ON” time with non-troublesome dyskinesia.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
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 |
Belgium |
Chile |
Czech Republic |
Denmark |
France |
Germany |
Hungary |
Israel |
Italy |
Netherlands |
Poland |
Portugal |
Russian Federation |
Serbia |
Spain |
Ukraine |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |