Clinical Efficacy & Safety of AP CD/LD in Fluctuating Parkinson’s Disease

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2015-003512-20-GB
• Date of registration: 03/03/2016
• Prospective Registration: Yes
• Primary sponsor: Intec Pharma, Ltd.
• Public title: Clinical Efficacy & Safety of AP CD/LD in Fluctuating Parkinson’s Disease
• Scientific title: A Phase III, Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled Study Comparing the Efficacy and Safety of Gastric Retentive, Controlled Release Accordion Pill™ Carbidopa/Levodopa (AP-CD/LD) to Immediate Release CD/LD in Fluctuating Parkinson’s Disease Patients
• Date of first enrolment: 28/04/2016
• Target sample size: 420
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003512-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Immediate Release Carbidopa/Levodopa comparator Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Germany, Hungary, Israel, Italy, Poland, Russian Federation, Slovakia, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Affairs
• Affiliation: Intec Pharma, Ltd.

• Name: Clinical Affairs
• Affiliation: Intec Pharma, Ltd.

Key inclusion & exclusion criteria

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
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. A valid diary record will not have more than 4 invalid entries (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
investigators 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 assessm
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
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)

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Parkinson's Disease
MedDRA version: 20.0 Level: HLT Classification code 10034005 Term: Parkinson's disease and parkinsonism System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: SINEMET 25-100
Product Name: Immediate Release carbidopa/levodopa 25/100 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Carbidopa
Other descriptive name: CARBIDOPA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: Levodopa
Other descriptive name: LEVODOPA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: Accordion Pill™ Carbidopa/Levodopa 50/400 mg
Pharmaceutical Form: Capsule
INN or Proposed INN: Carbidopa
Other descriptive name: CARBIDOPA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: Levodopa
Other descriptive name: LEVODOPA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Accordion Pill™ Carbidopa/Levodopa 50/500 mg
Pharmaceutical Form: Capsule
INN or Proposed INN: Carbidopa
Other descriptive name: CARBIDOPA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: Levodopa
Other descriptive name: LEVODOPA
Concentration unit: mg milligram(s)
Concentration typ

Primary Outcome(s)

Secondary Objective: Not applicable.

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 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.

Main Objective: 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.

Timepoint(s) of evaluation of this end point: End of Study (Week 26)

Secondary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: End of Study (Week 26)

Secondary ID(s)

2015-003512-20-HU

IN11004

NCT02605434

Source(s) of Monetary Support

Intec Pharma, Ltd.

Ethics review

Status: Approved
Approval date:
Contact: