E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Motor symptoms in Parkinson’s Disease. |
Sintomi motori del morbo di Parkinson |
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E.1.1.1 | Medical condition in easily understood language |
Symptoms related to movement due to Parkinson's disease (motor symptoms)
or
Parkinson symptoms related to movement (motor symptoms) |
Morbo di Parkinson |
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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 |
The purpose of this study is to evaluate whether the DopaFuse System can reduce the fluctuation of plasma levodopa levels as compared to participants’ standard intermittent doses of oral LD/CD tablets (background treatment). |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess whether the DopaFuse system is safe, well tolerated, and can relieve motor symptoms.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of Parkinson’s Disease consistent with UK Brain Bank Criteria
2. Age at least 30 years old at time of consent
3. Male and Female participants (Women of child-bearing potential (WOCB) are eligible for participation if they are not pregnant or breastfeeding and agree to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 30 days after the last dose of study treatment)
4. Suitable for oral retainer wear
5. A good response to Levodopa, as assessed by the Investigator
6. At least 2 hours of wearing OFF time per day, as reported by the participant
7. Predictable early morning OFF periods, in the judgement of the participant and the Investigator
8. Taking 400-1,200 mg of LD/CD per day in at least 4 doses, with stable dosing for the last 28 days prior to screening.
9. A modified Hoehn and Yahr of 3 in the ON state at screening
10. A stable regimen of anti-PD medications for the last 28 days prior to Screening
11. A Mini-Mental State Examination (MMSE) Score ≥26
12. Capable of giving signed informed consent
Approved for entry into the study by the Enrollment |
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E.4 | Principal exclusion criteria |
1. Atypical or secondary Parkinson’s Disease
2. Severe Dyskinesia that might interfere with study performance in the judgement of Investigator
3. Clinically significant dysphagia or sialorrhea that might interfere with administration of study intervention in the judgement of the Investigator
4. Use of extended release levodopa within 28 days prior to screening
5. Any clinically significant medical, surgical, or psychiatric condition; laboratory value or ECG result which, in the opinion of the Investigator, makes the participant unsuitable for study entry or potentially unable to complete all aspects of the study.
6. Presence of clinically significant orthostatic hypotension at screening, in the opinion of Investigator or the EAC
7. Suicidal ideation within 1 year prior to the Screening Visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia Suicide Severity Rating Scale (C-SSRS) or attempted suicide within the last 5 years.
8. History of psychosis or hallucinations in the past six months
9. Any malignancy in the past 5 years (excluding basal cell carcinoma of the skin or cervical carcinoma in situ that have been successfully treated.)
10. Current or previous diagnosis of malignant melanoma or the presence of any suspicious skin lesion based on physical exam findings
11. Unable to give blood required for the study
12. History of allergic reaction to plastics
13. LD infusion therapy (i.e. Duodopa); current or previous continuous apomorphine infusion treatment.
14. Participation in any other clinical trial <30 days prior to screening visit.
15. Presence of two third molars (“wisdom teeth”) on the upper dentition
16. Participants who, for any reason, are judged by the Investigator or the EAC to be inappropriate for this study, including participants who are unable to communicate or cooperate with the Investigator or who have/had a clinically significant illness or abnormal physical examination that may compromise safety of the participant during the trial or affect ability of the participant to adhere to study procedures.
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E.5 End points |
E.5.1 | Primary end point(s) |
PHARMACOKINETICS:
- Variability in plasma concentration of levodopa as assessed with the Levodopa Fluctuation Index (Cmax-Cmin)/Caverage), comparing Day 2 to Day 1 in steady state (4-12 hours). Fluctuation index will also be calculated by the hour.
SAFETY AND TOLERABILITY:
- TEAEs
- SAEs
- TEAEs leading to discontinuation
- Percent of participants that complete study
EFFICACY:
- Difference in OFF time between Days 1 and 15, based on in-person investigator ratings |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PK: Day 1 to 2
Efficacy: Day 1 to Day 15
Safety: Day 1 to Day 29 |
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E.5.2 | Secondary end point(s) |
PHARMACOKINETICS:
- Coefficient of variation (CV) for plasma levodopa. This will be calculated between 4 and 12 hours on Days 1 and 2 comparing DopaFuse and oral levodopa tablets.
- Variability in plasma concentration of levodopa as assessed with the Levodopa Fluctuation Index (Cmax-Cmin)/Caverage), comparing Day 3 to Day 1, as well as Day 2 (0-12 hours) to Day 1. Fluctuation index will also be calculated by the hour.
- Levodopa and Carbidopa Cmax, Tmax, and AUC
- Variability in plasma levodopa comparing Dopafuse and oral levodopa tablets based on fluctuation index and CV in participants who are H. pylori negative/positive
SAFETY AND TOLERABILITY:
- QUIP-RS
- C-SSRS
EFFICACY:
- Change in OFF time between Day 1 and Day 3
- Change in ON time without troublesome dyskinesia between Days 1, 3 and 15
- Change in on time with troublesome (severe) dyskinesia between Days 1, 3 and 15
- Change in UPDRS III at 6 hours after morning dose between Days 1, 3 and 15
- A comparison of the subgroups who are H. pylori positive and negative will be performed as an exploratory analysis.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK: Day 1 to Day 3
Safety&Tolerability: Day 15 and Day 29
Efficacy: Day 1-15 |
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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 | 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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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Last visit of the last participant in the study, OR
Last scheduled procedure shown in the Schedule of Activities for the last participant in the trial globally. |
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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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |