| 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 | 20.0 |
| 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 efficacy, safety and tolerability of Accordion Pill
carbidopa/levodopa (AP-CD/LD) compared to Immediate Release
carbidopa/levodopa (IR-CD/LD) 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 safety and tolerability. |
|
| E.3 | Principal inclusion criteria |
General Study Inclusion Criteria:
1. Subjects must be approved for suitability by an Enrollment Approval
Committee that is assembled of PD clinical experts
2. Able and willing to give written (signed and dated) informed
consent, which includes compliance with study requirements and
restrictions prior to admission to the study and adhere to visit schedule
and available to complete the study
3. Men or women 30 years of age and higher at initial screening
assessment. For the 100 subjects who enter the Gastroscopy sub-study,
the age limits are 30-80 years of age, inclusive, at initial screening
assessment.
4. Diagnosed with Parkinson's disease, consistent with UK brain bank
criteria
5. Has a good response to levodopa and is taking at least 4 doses of a
levodopa containing medication (or 3 doses of Rytary) per day during
waking hours (not including nighttime long acting levodopa) at a stable
dose for at least 28 days prior to initial screening assessment
XML File Identifier: v4yRLre1AF/ndwv1wdZtMiaiB4M=
Page 19/32
6. Other Anti-PD treatment (such as dopamine agonists, selective MAOB
inhibitors, anticholinergic agents or amantadine) are permitted if
stable for at least 28 days prior to study entry and provided they are not
anticipated to be changed during the course of the study
7. Total LD immediate release daily dose of 400mg to 1300 mg or
equivalent prior to initial screening assessment. Specifically, for Rytary,
doses up to 1755 mg daily are acceptable
8. Able to complete a 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 after training has been
completed. A valid diary record will not have more than 4 invalid entries
(i.e. double or missed entries)
9. At least 2.5 hours "Off time" per day during waking hours on
Screening 2-Day practice Hauser Home Diary, (morning akinesia should
be incorporated into the total "Off time" assessment)
10. Other than PD, the subject is in satisfactory health, as assessed by
physical examination and screening tests. No clinically significant
medical, psychiatric or laboratory abnormality that could compromise
safety or interfere with study procedures in the opinion of either the
investigator or the Enrollment Approval Committee/Sponsor.
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
visit.
Gastroscopy sub-study inclusion criteria:
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 30 and 80 years of age, inclusive, at initial
screening assessment
2. Willingness to undergo two gastroscopies during the study period
and to sign a separate informed consent form
3. No contraindications for sedation / anesthesia |
|
| 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. Clinically significant cardiac, pulmonary, hepatic or renal disease or
other condition which contraindicates his/her participation in the
opinion of either the investigator or the Enrollment Approval
Committee/Sponsor.
4. Severe dyskinesia in the opinion of either the investigator or the
Enrollment Approval Committee
5. Treatment with non-selective monoamine oxidase (MAO) inhibitors
during the last 28 days prior to initial screening assessment or planning
to take during study participation
6. Previous or planned neurosurgical treatment for Parkinson's Disease
(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
XML File Identifier: v4yRLre1AF/ndwv1wdZtMiaiB4M=
Page 20/32
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. Current or previous treatment for more than 28 days within the past
2 years with any neuroleptic drug (antipsychotic) or any other drug with
anti-dopaminergic properties (e.g. metoclopramide, domperidone).
10. Currently experiencing or any known history of psychosis or
delusions within 2 years prior to Screening.
11. Known history of substance abuse within the past 2 years
12. Moderate or greater level of alcohol consumption
13. Unable to swallow large pills (e.g., large vitamin pills)
14. History of Melanoma or suspicious skin lesion which could be a
Melanoma
15. Narrow-angle Glaucoma
16. History of small bowel or gastric surgery (Including PEG-J
placement for Duopa/Duodopa) or bowel obstruction, diagnosis of small
bowel narrowing, diagnosis of Crohn's disease, or frequent nausea or
emesis, regardless of etiology. (Previous appendectomy or hernioplasty
will not be exclusionary.
17. Active peptic ulcer disease or a history of peptic ulcer or upper GI
bleeding
18. Regular use of opioids (Intermittent opioid use is not exclusionary)
19. Symptomatic gastroparesis with frequent vomiting (at least once a
week)
20. Concomitant use of NSAIDs and oral steroids within the past 28
days
21. Allergy to the study drug or any of its excipients, or to Yellow Dye
#5 (tartrazine)
22. 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: True abstinence when
this is in line with the preferred and usual lifestyle of the subject, 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 through the end of the study
(End of study visit or final follow-up phone visit, whichever is later).
Hormonal contraceptive therapy must be a stable dose for at least 90
days prior to first study drug administration.
Gastroscopy sub-stuy exclusion criteria:
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
regular use of NSAIDs, use of aspirin (ASA) at a dose higher than 100
mg per day, iron supplements >30mg/day, or treatment with any of
these drugs above the specified doses/ regular use of NSAIDs within the
28 days prior to initial Screening assessment. (Intermittent use of
NSAIDs is not exclusionary).
2. Any clinically significant, abnormal gastric mucosal initial
gastroscopic finding of an erosion, ulcer (of any size) or tumor, as per
independent gastroenterologist's review |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint for this study is the change from Baseline
to EOS in the percentage of daily "Off time" during waking hours based
XML File Identifier: uDiIULYQs4rjWBXXdZ5rhD8Kgbk=
Page 21/32
on Hauser Home Diary assessments. Total number of "Off " hours
normalized to a 16- hour waking day will also be calculated but only a
single p-value applicable to both the percentage and hours will be
reported. |
|
| 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 in "On time" without troublesome
dyskinesia during waking hours
2. Change from Baseline to EOS in the number of daily Levodopa doses
3. CGI-I at EOS as recorded by physician
4. CGI-I at EOS as recorded by patient
5. Change from Baseline in total UPDRS Score (Sum of Parts I-III)
6. Change from Baseline to EOS in UPDRS Part II (Activities of Daily
Living)
7. Change from Baseline to EOS in UPDRS Motor Examination (part III -
evaluated 2-3 hours after last LD dose)
8. Change from Baseline to EOS in PDQ-39 summary index
9. Change from Baseline to EOS in troublesome dyskinesia
10. Change from Baseline to EOS in "On time" without dyskinesia during
waking hours. |
|
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 68 |
| 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 |
| 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 | 2 |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
