| 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 | 19.0 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10034005 |
| E.1.2 | Term | Parkinson's disease and parkinsonism |
| 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 safety, tolerability and efficacy of Accordion Pill carbidopa/levodopa compared to Immediate Release carbidopa/levodopa in fluctuating Parkinson's Disease patients. |
|
| E.2.2 | Secondary objectives of the trial |
|
| 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 |
Gastroscopy Sub-Study:
The gastroscopy sub-study is designed to evaluate the effect of the Accordion Pill on the gastric mucosa and to establish the long-term Accordion Pill tolerability. |
|
| E.3 | Principal inclusion criteria |
General Study Inclusion Criteria:
1. Men or women between 35 and 85 years of age, inclusive, at initial screening assessment. For the first 100 subjects the age limits are 35-70 years of age, inclusive, at initial screening assessment.
2. Diagnosed with idiopathic Parkinson's disease.
3. Has a good response to levodopa in the opinion of the investigator, and is taking at least 4 doses of levodopa containing medication per day.
4. Anti-PD treatment (such as levodopa formulations, dopamine agonists, selective MAO-B inhibitors, anticholinergic agents or amantadine) at a stable dose in the last 30 days prior to initial screening assessment.
5..Total LD total daily dose of 400 to 1300 mg in at least four divided doses prior to initial screening assessment
6..At least 2.5 hours Off time per day on average (not including morning akinesia), prior to screening. Subject should have at least 1 hour Off time on any given day.
7. Able to adhere to the visit schedule and protocol requirements, and available to complete the study.
8. Able to complete Hauser home diary and can tell the difference between "On and Off" time.
a. Achieved at least 75% diary concordance with an approved site rater in a 4-hour training session including at least one Off time assessment.
b. Returned a valid 2-day practice diary. A valid diary record will not have more than 4 invalid entries (double or missed entries).
9. Prepared and able to give written (signed and dated) informed consent, which includes compliance with study requirements and restrictions prior to admission to the study.
10. Other than PD, the subject is in satisfactory health, as assessed by physical examination and screening tests. No abnormality on clinical examination and screening tests that in the opinion of the investigator will compromise safety or interfere with study procedures.
11. Living in an area that is within 3 hours driving distance from the study site or is willing to stay in such a place the night before each study site visit.
Inclusion Criteria for the AP-CD/LD Conversion Period:
Subjects will enter the AP-CD/LD Conversion period if at the end of Harmonization and Stabilization period they continue to fulfill the following inclusion criteria:
1. Total LD daily dose of 400 to 1300 mg in at least four divided doses.
2. At least 2.5 hours Off time per day on average (not including morning akinesia) as documented in Hauser home diary. Subjects should have at least 1 hour Off time on any given day.
Inclusion Criteria for Gastroscopy Sub-Study:
Subjects entering the study in the period when gastroscopy examinations are required will have to comply with the following additional requirements:
1. Men or women between 35 and 70 years of age, inclusive, at initial screening assessment.
2. Willingness to undergo two gastroscopies during the study period.
3. No contraindications for sedation.
|
|
| E.4 | Principal exclusion criteria |
General Study Exclusion Criteria:
1. Participation in another drug clinical trial within 28 days prior to initial screening assessment (calculated from the previous study's last dosing date).
2. Atypical Parkinsonism (subjects with Parkinsonian features caused by disorder such as multiple system atrophy, progressive supranuclear palsy, dementia with Lewy bodies or multiple brain infarcts).
3. Significant history of cardiac, pulmonary, hepatic or renal disease or other condition or any major complication/illness which, in the opinion of the investigator, contraindicates his/her participation.
4. Treatment with COMT inhibitors during the last 14 days prior to initial screening assessment.
5. Received within 4 weeks prior to initial screening assessment or planning to take during study participation: non-selective monoamine oxidase (MAO) inhibitors.
6. Previous or planned neurosurgical treatment for PD (e.g., procedures including ablation or deep brain stimulation) during the course of the study.
7. Significant cognitive impairment as defined by the Mini-Mental State Examination (MMSE) score <26.
8. Clinically significant psychiatric illness, including major depression (Hamilton Depression Rating Scale-17 ≥ 14). Subjects with a lifetime history of suicidal attempt (including an active attempt, interrupted attempt or aborted attempt).
9. History of alcohol or substance abuse within the past 2 years.
10. Unable to swallow large pills (e.g., large vitamin pills).
11. History of melanoma or suspicious skin lesion which could be a melanoma.
12. Narrow-angle glaucoma.
13. History of small bowel or gastric surgery ( except for appendectomy or hernioplasty) or bowel obstruction, diagnosis of small bowel narrowing, diagnosis of Crohn's disease, or frequent nausea or emesis, regardless of etiology which, in the opinion of the investigator contraindicates his/her participation in the study.
14. Active peptic ulcer disease or a history of peptic ulcer or upper GI bleeding.
15. Current use of opioids.
16. Symptomatic gastroparesis with frequent vomiting (at least once a week).
17. Concomitant use of NSAIDs and oral steroids within the past 90 days.
18. Allergy to the study drug or any of its excipients, or to Yellow Dye #5 (tartrazine).
19. Women who are pregnant or nursing. Women of childbearing potential who are not willing to use a medically acceptable method of contraception. Medically acceptable methods of contraception that may be used by the subject and /or partner include, but not limited to: oral contraceptive agents, intrauterine devices (IUDs), implantable contraceptives (e.g., Norplant), transdermal hormonal contraceptives (e.g., Ortho-Evra), and injectable contraceptives (e.g., Depo-Provera), condom and /or diaphragm, diaphragm with vaginal spermicide, surgical sterilization (6 months), or postmenopausal females ( no menstrual period for > 2years) or vasectomy ( > 6 months) . The current contraceptive therapy must be maintained for the duration of the study. Hormonal contraceptive therapy must be a stable dose for at least 90 days prior to first study drug administration.
Exclusion Criterion for the Gastroscopy Sub-Study:
Subjects who meet the exclusion criterion listed below will not be eligible for the study during the period of the safety sub-study:
1. Current treatment with drugs known to induce gastric ulcers such as NSAIDs, aspirin at a dose higher than 100 mg per day, iron supplements >30mg/day or bisphosphonates, or treatment with any of these drugs within the 28 days prior to initial Screening assessment. In addition, subjects could not have a total of >7 days use of any of these drugs in the 29-90 days prior to initial Screening assessment.
Subjects who meet the exclusion criterion listed below in the baseline gastroscopy will not be eligible to continue to the Treatment period of the safety sub-study:
2. An abnormal baseline gastroscopic finding including any finding related to the gastric mucosa other than petechiae.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint for this study is the change from baseline (Week 5) to EOS (Week 26) in the percentage of daily Off time during waking hours based on 3-days by week average of the Hauser home diaries. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. Change from baseline to EOS of daily Off time (hours).
2. Change from baseline to EOS of On time without troublesome dyskinesias (hours).
3. Change from baseline to EOS in the number of daily LD doses
4. Improvement as recorded on CGI-I (patient and physician).
5. Change from baseline to EOS of On time with troublesome dyskinesias (hours).
6. Change from baseline to EOS in PDQ-39.
7. Change from baseline to EOS in the Scales for Outcomes in Parkinson's Disease PDSS-2.
8. Change from baseline to EOS in UPDRS Activities of Daily Living and Motor Examination (parts 2 and 3).
|
|
| 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 | 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 | 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) | 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 | Yes |
| E.8.2.3.1 | Comparator description |
| Immediate Release Carbidopa/Levodopa comparator |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 74 |
| 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 |
| Bulgaria |
| Germany |
| Hungary |
| Israel |
| Italy |
| Poland |
| Russian Federation |
| Slovakia |
| Spain |
| Ukraine |
| United Kingdom |
| United States |
|
| 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
|
|
| 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 | 9 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 9 |
Print
