A Study to Assess the Safety and Efficacy of the of the Gastric-retentive AP-CD/LD in Advanced Parkinson's Patients

Phase 3

• Conditions: Parkinson's Disease
• Interventions: Drug: Sinemet®; Drug: Accordion Pill™ Carbidopa/Levodopa; Drug: Placebo- Sinemet; Drug: Placebo -AP-CD/LD

• Registration Number: NCT02605434
• Lead Sponsor: Intec Pharma Ltd.

Brief Summary

The purpose of this study is to determine whether the gastric retentive Accordion Pill™ Carbidopa/Levodopa (AP-CD/LD) is more effective than the commercially available immediate release Carbidopa/Levodopa in reducing motor fluctuations such as "off time" in advanced Parkinson's Disease patients.

Detailed Description

A multi-center, global, randomized, double-blind, double-dummy, active-controlled, parallel-group study in adult subjects with fluctuating PD. The study will have 2 open label Titration periods of 6 weeks each prior to the double blind Maintenance period. In the open label periods all patients will be stabilized on the active comparator Sinemet® and then on AP-CD/LD. The double blind Maintenance period will be 13 weeks long.

Study Timeline

• Study First Submitted: 2015-11-05
• Study First Submitted QC: 2015-11-11
• Study First Posted: 2015-11-16
• Study Start: 2016-03
• Status Verified: 2018-04
• Primary Completion: 2019-07
• Last Update Submitted: 2019-08-07
• Last Update Posted: 2019-08-08
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 420

Inclusion Criteria

1. Subjects must be approved for suitability by an Enrollment Approval Committee

2. Able and willing to give written (signed and dated) informed consent 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 MAO-B 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 400 mg 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

   1. Achieved at least 75% diary concordance with an approved site rater in a 4-hour training session including at least one "Off time" assessment
   2. Returned a valid 2-day practice diary after training has been completed.

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

Main

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 or any major complication/illness 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 1 month 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SINEMET®	Sinemet®	IR Carbidopa/ levodopa tablets 25/100 mg at least 4 times a day and placebo AP-CD/LD
AP-CD/LD	Accordion Pill™ Carbidopa/Levodopa	Accordion Pill™ Carbidopa/Levodopa Capsule 50/400mg , b.i.d or t.i.d or Accordion Pill™ Carbidopa/Levodopa Capsule 50/500mg , b.i.d or t.i.d and Placebo IR Carbidopa/ levodopa
SINEMET®	Placebo- Sinemet	IR Carbidopa/ levodopa tablets 25/100 mg at least 4 times a day and placebo AP-CD/LD
AP-CD/LD	Placebo -AP-CD/LD	Accordion Pill™ Carbidopa/Levodopa Capsule 50/400mg , b.i.d or t.i.d or Accordion Pill™ Carbidopa/Levodopa Capsule 50/500mg , b.i.d or t.i.d and Placebo IR Carbidopa/ levodopa

Primary Outcome Measures

Name	Time	Method
Change from Baseline through study completion, an average of 27 weeks, in the percentage of daily "Off time" during waking hours	Baseline through study completion, an average of 27 weeks	Change from Baseline through study completion, an average of 27 weeks, 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.

Secondary Outcome Measures

Name	Time	Method
Change from Baseline through study completion, an average of 27 weeks, in total UPDRS Score (Sum of Parts I-III)	Baseline through study completion, an average of 27 weeks
Change in the number of total daily LD doses from Baseline through study completion, an average of 27 weeks (hours)	Baseline through study completion, an average of 27 weeks
CGI-I through study completion, an average of 27 weeks, as recorded by physician & patient	Baseline through through study completion, an average of 27 weeks,
Change from Baseline through study completion, an average of 27 weeks, in "On time" without troublesome dyskinesia during waking hours	Baseline through study completion, an average of 27 weeks

Trial Locations

Locations (95)

University Alabama Hospital Neurology; 🇺🇸 Birmingham, Alabama, United States

Saint Joseph's Hospital and Medical Center Muhammad Ali Parkinson Research Center; 🇺🇸 Phoenix, Arizona, United States

Parkinson's Disease & Movement Disorders Center, Dept of Neu; 🇺🇸 Fountain Valley, California, United States

Loma Linda University Medical Center; 🇺🇸 Loma Linda, California, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

SC3 Research; 🇺🇸 Reseda, California, United States

UC Davis Medical Center; 🇺🇸 Sacramento, California, United States

University of Colorado Dept. of Neurology; 🇺🇸 Aurora, Colorado, United States

Hartford HealthCare; 🇺🇸 Vernon, Connecticut, United States

Parkinson's Disease and Movement Disorders Center of Boca Raton; 🇺🇸 Boca Raton, Florida, United States

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