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A Study of an Investigational Drug to See How it Affects the People With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes) Compared to an Approved Drug Used to Treat People With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)

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ClinicalTrials.gov Identifier: NCT03391882
Recruitment Status : Recruiting
First Posted : January 5, 2018
Last Update Posted : June 21, 2019
Sponsor:
Information provided by (Responsible Party):
Sunovion

Tracking Information
First Submitted Date  ICMJE January 2, 2018
First Posted Date  ICMJE January 5, 2018
Last Update Posted Date June 21, 2019
Actual Study Start Date  ICMJE December 19, 2018
Estimated Primary Completion Date March 24, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 5, 2018)
change from pre-dose to 90 minutes post-dose in MDS UPDRS Part III score after 4 weeks of dosing in each crossover period (assessed by the blinded-rater in-clinic at Visit 3 and Visit 6 of PART B). [ Time Frame: Week 4 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 2, 2018)
Percentage of subjects preferring sublingual APL-130277 (apomorphine) compared to percentage of subjects preferring subcutaneous APO-go (apomorphine). [ Time Frame: Over the entire study (approx. 85 days). ]
Change History Complete list of historical versions of study NCT03391882 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2018)
  • Durability of effect, defined as an Investigator confirmed full "ON" within 30 minutes post dose and at 90 minutes post-dose, after 4 weeks of dosing in each crossover period (assessed by the blinded-rater in-clinic at Visit 3 and Visit 6 of PART B). [ Time Frame: Week 4 ]
  • Subject preference for treatment regimen as measured by the Subject Preference Visual Analog Scale (VAS) after the subject has completed both APL 130277 and sc apomorphine treatment regimens (assessed in-clinic at Visit 6 of PART B). [ Time Frame: Week 4 ]
    with a recorded range of -50 to 50. Negative values indicate preference for SC treatment, and the more negative the value, the stronger is the preference for SC compared to APL treatment. Positive values indicate preference for APL treatment, and the more positive the value, the stronger is the preference for APL compared to SC treatment. A value of 0 indicates no preference of one treatment over the other.
  • Per the Expanded Home Dosing Diary, percent of "ON" episodes without troublesome dyskinesia based on the 3 consecutive days prior to Visit 2, Visit 3, Visit 5, and Visit 6. [ Time Frame: Week 4 ]
  • Subject confirmed durability of effect, defined as subject confirmed full "ON" within 30 minutes post-dose and at 90 minutes post-dose, after 4 weeks of dosing in each crossover period (assessed in-clinic at Visit 3 and Visit 6 of PART B). [ Time Frame: Week 4 ]
  • Patient Global Impression of Change (PGI-C): Subject improvement of "OFF" episodes, defined as very much better, much better or a little better after 4 weeks of dosing in each crossover period (assessed in-clinic at Visit 3 and Visit 6 of PART B). [ Time Frame: Week 4 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 2, 2018)
  • Mean change from pre-dose in MDS-UPDRS Part III Motor Examination score at 90 minutes post-dose. [ Time Frame: Part B Visit 3 and 6 (after 4 weeks of dosing in each crossover period of PART B) ]
  • MDS-UPDRS Part II Motor Aspects of Experiences of Daily Living. mean change from Screening in the MDS-UPDRS Part II sum score [ Time Frame: Part B V3 and 6 (after 4 weeks of dosing in each crossover period of PART B) ]
  • Patient Global Impression of Improvement (PGI):The percentage of subjects improved (ie, very much improved, much improved or minimally improved) [ Time Frame: Part B V3 and 6 (after 4 weeks of dosing in each crossover period of PART B) ]
  • Percentage of subjects without a worsening of troublesome dyskinesia (dyskinesia in the last month is less than usual) [ Time Frame: Part B V3 and 6 (after 4 weeks of dosing in each crossover period of PART B) ]
  • Parkinson's Disease Questionnaire-39 (PDQ-39) mean change from Screening in Summary Index score [ Time Frame: Part B V3 and 6 (after 4 weeks of dosing in each crossover period of PART B) ]
  • Percentage of subjects with investigator confirmed Full "ON" within 30 minutes post-dose [ Time Frame: Part B V3 and 6 (after 4 weeks of dosing in each crossover period of PART B) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of an Investigational Drug to See How it Affects the People With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes) Compared to an Approved Drug Used to Treat People With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)
Official Title  ICMJE An Open-Label, Randomized, Crossover Trial Utilizing a Single-Blinded Rater to Evaluate APL-130277 Compared to Subcutaneous Apomorphine in Levodopa Responsive Subjects With Parkinson's Disease Complicated by Motor Fluctuations
Brief Summary A study of an investigational drug to see how it affects the people with Parkinson's Disease complicated by motor fluctuations ("OFF" Episodes) compared to an approved drug used to treat people with Parkinson's Disease complicated by motor fluctuations ("OFF" Episodes)
Detailed Description

An Open-Label, Randomized, Crossover Trial utilizing a Single-Blinded Rater to evaluate APL-130277 compared to s.c. Apomorphine in Levodopa Responsive Subjects with Parkinson's Disease Complicated by Motor Fluctuations.

PART A consists of an open label, crossover titration phase where eligible subjects will be randomized to 1 of 2 treatment sequences in a 1:1 ratio to Sublingual APL 130277 followed by subcutaneous apomorphine or subcutaneous apomorphine followed by sublingual APL 130277. Subjects will undergo dose titration with the first study treatment (APL 130277 or sc apomorphine) to tolerance and effect, ie, the tolerable dose that turns the subject from the practically defined "OFF" state to the full "ON" state as determined by both the Investigator and subject. The subject will then be crossed over to the other study treatment (APL 130277 or subcutaneous apomorphine) and similarly titrated to tolerance and effect. These determined doses of APL 130277 and subcutaneous apomorphine will be used during PART B.

PART B consists of an open-label, crossover treatment period where subjects will be randomized to one of the study treatment for 4 weeks, then be crossed over to the other study treatment (APL-130277 or sc apomorphine) for additional 4-weeks of open-label treatment. Subjects return to the clinic for safety and efficacy assessments throughout the treatment period.

This study is designed to test the superiority of sublingually administered APL-130277 against subcutaneously injected apomorphine (APO-go) for the treatment of "OFF" episodes in patients with Parkinson's Disease, as measured by the change from pre-dose to 90 minutes post-dose in MDS UPDRS Part III score in Part B after 4 weeks of dosing in each crossover period.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Masking Description:

Open label: APL-130277 and Subcutaneous Apomorphine

Single-Blinded Rater for MDS-UPDRS Part III Motor Examination assessment in Part B.

Primary Purpose: Treatment
Condition  ICMJE Motor OFF Episodes Associated With Parkinson's Disease
Intervention  ICMJE
  • Drug: APL-130277
    APL-130277: Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A
    Other Name: Apomorphine Hydrochloride
  • Drug: subcutaneous apomorphine
    subcutaneous apomorphine Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A
    Other Name: APO-go®
Study Arms  ICMJE
  • Experimental: APL-130277
    APL-130277: Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A
    Intervention: Drug: APL-130277
  • Active Comparator: subcutaneous apomorphine
    subcutaneous apomorphine , Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A
    Intervention: Drug: subcutaneous apomorphine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 5, 2018)
106
Original Estimated Enrollment  ICMJE
 (submitted: January 2, 2018)
85
Estimated Study Completion Date  ICMJE March 24, 2020
Estimated Primary Completion Date March 24, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. The subject (and caregiver, if applicable) must be fully informed of and understand the objectives, procedures, and possible benefits and risks of the study, and give written informed consent prior to performing any study related activities.
  2. Male or female ≥ 18 years of age.
  3. Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion).
  4. Clinically meaningful response to levodopa (L-Dopa), as determined by the Investigator.
  5. Subjects at screening must demonstrate an adequate L-Dopa response on the MDS UPDRS Part III in the "ON" state compared to the MDS UPDRS Part III in the "OFF" state and on the Hoehn and Yahr, as determined during the review by Enrollment Adjudication Committee (EAC), Sponsor, and Medical Monitor.
  6. Receiving stable doses of L Dopa/carbidopa and/or L Dopa/benserazide and/or L Dopa/carbidopa/entacapone (immediate or chronic release) administered at least 4 times per day OR Rytary™ administered at least 3 times per day for at least 4 weeks before the initial screening Visit (SV1). Adjunctive PD medication regimens are permitted but must be maintained at a stable dose for at least 4 weeks prior to SV1 with the exception of monoamine oxidase B (MAO B) inhibitors, which must be maintained at a stable level for at least 8 weeks prior to SV1.
  7. No planned medication change(s) or surgical intervention anticipated during the course of study.
  8. Subjects must experience at least one well defined "OFF" episode per day and have a total daily "OFF" time duration of > 2 hours during the waking day, based on judgment of physician and subject self assessment.
  9. Subject must have predictable morning "OFF" periods, based on judgment of physician and subject self assessment.
  10. Subject, and where appropriate caregiver, must be trained in completing the home dosing diaries and able to recognize "ON" and "OFF" states.
  11. Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
  12. Mini-Mental State Examination (MMSE) score > 25.
  13. Female subject of childbearing potential and male subject with female partner of childbearing potential must agree to either remain abstinent or use adequate and reliable contraception throughout the study and for at least 7 days after the last dose of study drug has been taken. Note: Continued use of adequate and reliable contraception is recommended through 30 days after study completion.
  14. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study related procedures to complete the study.
  15. Must be approved as a satisfactory candidate by the Enrollment Adjudication Committee (EAC), Medical Monitor, and Sponsor.

Exclusion Criteria:

  1. Atypical or secondary parkinsonism.
  2. Major focal brain disorders including malignancy or stroke.
  3. Prior treatment with any of the following: a neurosurgical procedure for PD; continuous subcutaneous (subcutaneous) apomorphine infusion; subcutaneous (subcutaneous) apomorphine injection; Duodopa/Duopa; or APL-130277.
  4. Contraindications to domperidone, subcutaneous apomorphine, or hypersensitivity to apomorphine hydrochloride or any of the ingredients of subcutaneous apomorphine (notably sodium metabisulfite).
  5. Female who is pregnant or lactating.
  6. Participation in an interventional clinical study and/or receipt of any investigational (ie, unapproved) medication within 30 days prior to SV1.
  7. Currently taking selective 5HT3 antagonists (ie, ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine or clozapine) or dopamine depleting agents. Subjects receiving anti depressants must be on a stable daily dose for at least 8 weeks prior to SV1.
  8. The subject has a current diagnosis or history of substance abuse (excluding nicotine and caffeine) or alcohol abuse (in the opinion of the investigator) < 6 months prior to SV1.
  9. The recreational use of cannabinoids and hallucinogenic are excluded, as well any use of a sublingual formulation of any drug.
  10. Subject has a history of malignancy within 5 years prior to SV1, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
  11. Subject has a clinically significant abnormality on screening evaluation including physical examination, vital signs, electrocardiogram (ECG), or laboratory tests that the Investigator considers to be inappropriate to allow participation in the study.
  12. Subject has screening laboratory test results of: blood urea nitrogen (BUN) value ≥ 1.5 times the upper limit of normal (ULN) for the reference range; serum creatinine > 1.5 times the ULN for the reference range; or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value ≥ 2 times the ULN for the reference laboratory.
  13. Subject has random (non-fasting) screening glucose of ≥ 200 mg/dL (11.1 mmol/L) or HbA1c > 7.0%.
  14. Subjects with type 1 diabetes, or insulin dependent diabetics are excluded. Subjects with type 2 diabetes are eligible for study inclusion if the following conditions are met:

    • Subject's screening glucose is < 200 mg/dL (11.1 mmol/L). Note: Subjects with random (non fasting) blood glucose at screening ≥ 200 mg/dL (11.1 mmol/L) must be retested in a fasted state; and
    • Subject's hemoglobin A1c (HbA1c) ≤ 7.0%; and
    • If the subject is currently being treated with oral anti-diabetic medication(s), the dose must have been stable for at least 4 weeks prior to SV1. Such medication may be adjusted or discontinued during the study, as clinically indicated.
  15. The subject's screening ECG results of corrected QT interval using Fridericia's formula (QTcF) ≥ 450 msec for male subjects or ≥ 470 msec for female subjects. Eligibility will be based on the core laboratory ECG interpretation report.
  16. Subject has a positive screening laboratory test result for human immunodeficiency virus (HIV).
  17. Subject has a positive screening laboratory test result for hepatitis B surface antigen or hepatitis C antibodies and has liver function test results at screening above the ULN for the reference laboratory.
  18. Subject has any other medical disorder that, in the opinion of the Investigator, could interfere with the subject's participation in the study.
  19. Subject has major psychiatric disorder(s), including but not limited to: bipolar disorder, psychosis (eg, Parkinson's Disease Psychosis), major depressive episode, or any disorder that, in the opinion of the Investigator, would require treatment that could make study participation unsafe or make treatment compliance difficult.
  20. History of clinically significant impulse control disorder(s).
  21. History of symptomatic orthostatic hypotension requiring medication.
  22. History of severe dyskinesia based on a score of 4 on the MDS-UPDRS Part IV.
  23. Dementia that precludes providing informed consent or would interfere with participation in the study.
  24. Current/recent suicidal ideation as evidenced by answering "yes" to "Suicidal Ideation" item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS assessment at screening (using the "screening /Baseline Version" scale, in the past 12 months) or attempted suicide within the last 5 years.
  25. Presence of canker or mouth sores in the 30 days prior to SV1, or other clinically significant oral pathology in the opinion of the Investigator. The Investigator should follow-up with an appropriate specialist on any finding, if indicated, before enrolling a subject into the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: CNS Medical Director 1-866-503-6351 clinicaltrialdisclosure@sunovion.com
Listed Location Countries  ICMJE Austria,   France,   Germany,   Italy,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03391882
Other Study ID Numbers  ICMJE CTH-302
2016-003456-70 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sunovion
Study Sponsor  ICMJE Sunovion
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: CNS Medical Director Sunovion
PRS Account Sunovion
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP