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An Open-Label Phase 3 Study to Examine the Long-Term Safety, Tolerability and Efficacy of APL-130277 for the Acute Treatment of "OFF" Episodes in Patients With Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT02542696
Recruitment Status : Recruiting
First Posted : September 7, 2015
Last Update Posted : March 22, 2018
Sponsor:
Information provided by (Responsible Party):
Sunovion

Brief Summary:
A 24-week, prospective, multi-center, open-label, Phase 3 study in L-Dopa responsive PD patients with motor fluctuations ("OFF" episodes), designed to evaluate the long-term safety, tolerability and efficacy of APL-130277.

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: APL-130277 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 226 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 3 Study Examining the Long-Term Safety, Tolerability and Efficacy of APL-130277 in Levodopa Responsive Patients With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)
Actual Study Start Date : August 31, 2015
Estimated Primary Completion Date : January 1, 2020
Estimated Study Completion Date : January 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: APL-130277
APL-130277 sublingual thin film (10 mg, 15 mg, 20 mg, 25 mg, 30 mg and 35 mg)
Drug: APL-130277
Used to treat up to 5 "OFF" episodes per day
Other Name: Apomorphine Hydrochloride, Sublingual Thin Film




Primary Outcome Measures :
  1. Evaluation of safety and tolerability data collected, including 12-lead ECGs, orthostatic hypotension, oropharyngeal and dopaminergic AEs, and other pertinent safety parameters. [ Time Frame: Throughout the entire study ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

De Novo Patients:

Inclusion Criteria

  1. Male or female ≥ 18 years of age.
  2. Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion) .
  3. Clinically meaningful response to L-Dopa as determined by the Investigator.
  4. Receiving stable doses of L-Dopa/carbidopa (immediate or CR) 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 must be maintained at a stable dose for at least 4 weeks prior to the initial Screening Visit (SV1) with the exception that MAO-B inhibitors must be maintained at a stable level for at least 8 weeks prior to the initial Screening Visit (SV1).
  5. No planned medication change(s) or surgical intervention anticipated during the course of study.
  6. Patients must experience at least one well defined "OFF" episode per day with a total daily "OFF" time duration of ≥ 2 hours during the waking day, based on patient self assessment.
  7. Patient and/or caregiver must be trained in performing home dosing diary assessments of the motor state and must be able to recognize "ON" and "OFF" states.
  8. Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
  9. MMSE score > 25.
  10. If female and of childbearing potential, must agree to be sexually abstinent or use one of the following highly effective methods of birth control:

    • Hormonal contraceptives (eg, combined oral contraceptives, patch, vaginal ring, injectables, and implants);
    • Intrauterine contraceptive system; Protocol CTH-301, Version 4.00 APL-130277 Confidential and Proprietary 57 30 May 2017
    • Surgical sterilization or partner sterile (must have documented proof); AND

    One of the following effective methods of birth control:

    • Male/female condom;
    • Cervical cap with spermicide;
    • Diaphragm with spermicide;
    • Contraceptive sponge.
  11. Male subjects must be either surgically sterile, agree to be sexually inactive or use a double-barrier method of birth control (eg, condom and diaphragm with spermicide, condom with cervical cap and spermicide) from first study drug administration until 90 days after final drug administration.
  12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures.
  13. Able to understand the consent form, and to provide written informed consent.

Exclusion Criteria

  1. Atypical or secondary parkinsonism.
  2. Previous treatment with any of the following: a neurosurgical procedure for PD;continuous s.c. apomorphine infusion; Duodopa/Duopa; or APL-130277.
  3. Treatment with any form of s.c. apomorphine within 7 days prior to the second Screening Visit (SV2). Patients that stopped s.c. apomorphine for any reason other than systemic safety concerns or lack of efficacy may be considered.
  4. Contraindications to APOKYN®, or hypersensitivity to apomorphine hydrochloride or any of the ingredients of APOKYN® (notably sodium metabisulfite).
  5. Female who is pregnant or lactating.
  6. Participation in a clinical trial within 30 days prior to the initial Screening Visit (SV1).
  7. Receipt of any investigational (ie, unapproved) medication within 30 days prior to the initial Screening Visit (SV1).
  8. Currently taking selective 5HT3 antagonists (ie, ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine or clozapine) or dopamine depleting agents.
  9. Drug or alcohol dependency in the past 12 months.
  10. Subject has a history of malignancy within 5 years prior to the Screening visit, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. Pituitary tumors of any duration are excluded.
  11. Clinically significant medical, surgical, or laboratory abnormality in the opinion of the Investigator.
  12. Major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis, or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
  13. History of clinically significant hallucinations during the past 6 months.
  14. History of clinically significant impulse control disorder(s).
  15. Dementia that precludes providing informed consent or would interfere with participation in the study.
  16. Current suicidal ideation within one year prior to the second Screening Visit (SV2) as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the C-SSRS or attempted suicide within the last 5 years.
  17. Donation of blood or plasma in the 30 days prior to first dosing.
  18. Presence of canker or mouth sores in the 30 days prior to the initial Screening Visit (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 patient into the study.

Patients Rolling Over from CTH-201, CTH-203, CTH-300, or CTH-302.(Rollover Patients):

Inclusion Criteria

  1. Completion of any of the following studies: CTH-201, CTH-203, CTH-300, or CTH-302; and, in the opinion of the Investigator, would benefit from continued treatment with APL-130277.
  2. No major increases in concomitant PD medications since completion of any of the following studies: CTH-201, CTH-203, CTH-300, or CTH-302. Any change in PD medications since the previous study should be discussed with the Medical Monitor to determine patient eligibility in the current study.
  3. If female and of childbearing potential, must agree to be sexually abstinent or use one of the following highly effective methods of birth control:

    • Hormonal contraceptives (eg, combined oral contraceptives, patch, vaginal ring, injectables, and implants);
    • Intrauterine contraceptive system;
    • Surgical sterilization or partner sterile (must have documented proof); AND

    One of the following effective methods of birth control:

    • Male/female condom;
    • Cervical cap with spermicide;
    • Diaphragm with spermicide;
    • Contraceptive sponge.
  4. Male subjects must be either surgically sterile, agree to be sexually inactive or use a double-barrier method of birth control (eg, condom and diaphragm with spermicide, condom with cervical cap and spermicide) from first study drug administration until 90 days after final drug administration.
  5. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures.
  6. Able to understand the consent form, and to provide written informed consent.

Exclusion Criteria

  1. Female who is pregnant or lactating.
  2. Presence of any major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis (including clinically significant hallucinations during the past 6 months) or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
  3. Presence of any clinically significant medical (including CNS or CV events), surgical, or laboratory abnormality that would make study participation unsafe or make treatment compliance difficult. Clinical significance to be determined by the Investigator.
  4. Receipt of any investigational (ie, unapproved) medication or participation in any clinical trial since completing a previous study using APL-130277.
  5. Development of canker or mouth sores since completing a previous clinical study using APL-130277. For other clinically significant oral pathology, the Investigator should follow-up with an appropriate specialist on any finding, if indicated, before enrolling such a patient into the study. Clinical significance to be determined by the Investigator.
  6. Current suicidal ideation as evidenced by answering "yes" to Question 4 or 5 on the suicidal ideation portion of the C-SSRS at the Screening Visit (SV1).

Completer Patients-patients who have previously completed CTH-301 study

Inclusion Criteria:

  1. Completion of the CTH-301 study, and in the opinion of the Investigator, would benefit from continued treatment with APL-130277.
  2. If female and of childbearing potential, must agree to be sexually abstinent or use one of the following highly effective methods of birth control:

    • Hormonal contraceptives (eg, combined oral contraceptives, patch, vaginal ring, injectables, and implants);
    • Intrauterine contraceptive system;
    • Surgical sterilization or partner sterile (must have documented proof); AND

    One of the following effective methods of birth control:

    • Male/female condom;
    • Cervical cap with spermicide;
    • Diaphragm with spermicide;
    • Contraceptive sponge.
  3. Male subjects must be either surgically sterile, agree to be sexually inactive or use a double-barrier method of birth control (eg, condom and diaphragm with spermicide, condom with cervical cap and spermicide) from first study drug administration until 90 days after final drug administration.
  4. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures.
  5. Able to understand the consent form, and to provide written informed consent.

Exclusion Criteria:

  1. Female who is pregnant or lactating.
  2. Presence of any major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis (including clinically significant hallucinations during the past 6 months) or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
  3. Presence of any clinically significant medical (including CNS or CV events), surgical, or laboratory abnormality that would make study participation unsafe or make treatment compliance difficult. Clinical significance to be determined by the Investigator.
  4. Receipt of any investigational (ie, unapproved) medication or participation in any clinical trial since completing the CTH-301 study.
  5. Development of canker or mouth sores since completing the CTH-301 study. For other clinically significant oral pathology, the Investigator should follow-up with an appropriate specialist on any finding, if indicated, before enrolling such a patient into the study. Clinical significance to be determined by the Investigator.
  6. Current suicidal ideation as evidenced by answering "yes" to Question 4 or 5 on the suicidal ideation portion of the C-SSRS at the Screening Visit Phase 2 (SVP2).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02542696


Contacts
Contact: CNS Medical Director 1-866-503-6351

  Hide Study Locations
Locations
United States, Alabama
University of Alabama Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Joseph Richardson    205-934-0074      
United States, Arizona
Muhammed Ali Parkinson and Movement Disorder Center/Barrow Neurological Institute Recruiting
Phoenix, Arizona, United States, 85013
Contact: Leslie Shelton    602-406-9593      
Movement Disorders Center of Arizona Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Susan Ortega    480-526-5441      
Mayo Clinic Arizona Withdrawn
Scottsdale, Arizona, United States, 85259
United States, California
The Parkinson's and Movement Disorder Institute Recruiting
Fountain Valley, California, United States, 92708
Contact: Briana Bruckler    714-378-5074      
UC Irvine Health Gottschalk Medical Plaza Recruiting
Irvine, California, United States, 92697
Contact: Jaclyn Alcazar    949-824-1114      
Keck Medical Center at USC Recruiting
Los Angeles, California, United States, 90033
Contact: Gina Barles    323-442-5723      
Research center of southern california Withdrawn
Oceanside, California, United States, 92056
United States, Colorado
University of Colorado School of Medicine Recruiting
Aurora, Colorado, United States, 80045
Contact: Haley Steinert, MD    303-724-4172      
United States, District of Columbia
MedStar Georgetown University Hospital Recruiting
Washington, District of Columbia, United States, 20007
Contact: Sasha Warren    202-444-6941      
United States, Florida
Parkinsons Disease and Movement Disorders Center Recruiting
Boca Raton, Florida, United States, 33486
Contact: Fannie Levinson    561-392-1818      
University of Miami, Miller School of Medicine Recruiting
Miami, Florida, United States, 33136
Contact: Silvia Vargas    305-243-3647      
Parkinson's Disease Treatment Center of Southwest Florida Recruiting
Port Charlotte, Florida, United States, 33980
Contact: Judy Seymour    941-743-4987      
Suncoast Neuroscience Associates Inc. Recruiting
Saint Petersburg, Florida, United States, 33713
Contact: Ian Lever    727-202-2623      
USF Parkinson's Disease and Movement Disorder Center Recruiting
Tampa, Florida, United States, 33613
Contact: Leigh Donharl    813-396-0763      
United States, Georgia
Emory University Department of Neurology Recruiting
Atlanta, Georgia, United States, 30329
Contact: Mary Louise Weeks    404-712-6999      
GRU Movement Disorders Recruiting
Augusta, Georgia, United States, 30912
Contact: Buff Farrow    706-721-0619      
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Anna Rutkowski    312-503-1999      
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Teresa Chmura    312-942-8002 ext 4      
NorthShore Neurological Institute B043D Recruiting
Glenview, Illinois, United States, 60026
Contact: Julie Anderson    847-503-4322      
Central DuPage Hospital - Neurodegenerative Clinic - Movement Disorders Center Recruiting
Winfield, Illinois, United States, 60190
Contact: Komal Sharma    630-933-6844      
United States, Iowa
University of Iowa Dept. of Neurology Recruiting
Iowa City, Iowa, United States, 52242
Contact: Jeri Sieren    319-356-8744      
United States, Kansas
Kansas University Medical Center-Department of Neurology Recruiting
Kansas City, Kansas, United States, 66160
Contact: April Langhammer    913-588-6989      
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Contact: Renee Wagner    859-323-0028      
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Katie Callison    443-827-0677      
Contact: Terra Hill    443-827-0677      
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21287
Contact: Erica Stacy    433-287-7850      
United States, Michigan
Michigan State University - Dept. of Neurology Recruiting
East Lansing, Michigan, United States, 48824
Contact: Doozie Russel    517-884-2274      
QUEST Research Institute Recruiting
Farmington Hills, Michigan, United States, 48334
Contact: Linda Bardram    248-957-8940      
Northern Michigan Neurology Withdrawn
Traverse City, Michigan, United States, 49684
Henry Ford Hospital Recruiting
West Bloomfield, Michigan, United States, 48322
Contact: Victoria Churchill    248-661-6270      
United States, Minnesota
Park Nicolet Institute - Stuthers Parkinson's Center Recruiting
Golden Valley, Minnesota, United States, 55427
Contact: Bradley Berrington    952-993-5903      
United States, New York
David L. Kreitzman, MD, PC Withdrawn
Commack, New York, United States, 11725
Bendheim Parkinson's and Movement Disorder Center (Mount Sinai Medical Center) Recruiting
New York, New York, United States, 10029
Contact: Joan Bratton    212-241-0279      
Contact: Mindy Lopez    212 241 0279      
Columbia University Medical Center - Neurological Institute, Movement Disorders Recruiting
New York, New York, United States, 10032
Contact: Amber Servi    212-305-3938      
United States, North Carolina
Duke University - Movement Disorders Clinic Recruiting
Durham, North Carolina, United States, 27705
Contact: Karen White-Tong    919-668-2905      
Raleigh Neurology Associates, P.A. Recruiting
Raleigh, North Carolina, United States, 27607
Contact: Joyce Schwartz    919-719-8826      
Wake Forest Baptist Health Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Jessica Dimos    336-716-8694      
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Kristy Espay    513-558-6517      
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Alexandra Wyant    216-444-1179      
Contact: Chris Firestone    2164455637      
The Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Allison Daley    614-688-8672      
Contact: Katherine Ambrogi    614-688-6685      
UT Gardner-McMaster Parkinson's Center Recruiting
Toledo, Ohio, United States, 43614
Contact: Julia Spears    419-383-6728      
United States, Oklahoma
The Movement Disorder Clinic of Oklahoma Recruiting
Tulsa, Oklahoma, United States, 74136
Contact: Shannon Klos    918-392-4530 ext 5      
United States, Pennsylvania
Jefferson University Hospital Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Lealh Shabo    215-503-3213      
Parkinson's Disease and Movement Disorders Center Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Reema Patel    215-829-7128      
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Shonna Jenkins    843-792-9115      
United States, Texas
Houston Methodist Neurological Institute Recruiting
Houston, Texas, United States, 77030
Contact: Chia Arif    713-363-8390      
East Texas Medical Center Recruiting
Tyler, Texas, United States, 75701
Contact: Jeanetta Patterson    903-531-8850      
United States, Virginia
University of Virginia Adult Neurology Recruiting
Charlottesville, Virginia, United States, 322903
Contact: Katie Sullivan    434-982-6599      
Sentara Neuroscience Institute Recruiting
Virginia Beach, Virginia, United States, 23456
Contact: Lisa Richardson    757-507-0642      
United States, Washington
Evergreen Health Recruiting
Kirkland, Washington, United States, 98034
Contact: Ann Fierro    425-899-3115      
Contact: Marsha Merrick    (425) 899-3115      
Swedish Neuroscience Research Recruiting
Seattle, Washington, United States, 98122
Contact: Lindsey Maassel    206-320-7121      
Canada, Ontario
UHN Toronto Western Hospital Active, not recruiting
Toronto, Ontario, Canada, M5T 2S8
United Kingdom
Kings College, The Maurice Wohl Neuroscience Institute Active, not recruiting
London, Greater London, United Kingdom
Manchester University Active, not recruiting
Salford, Greater Manchester, United Kingdom, M68HD
Newcastle University Active, not recruiting
Newcastle-upon-Tyne, Northumberland, United Kingdom, NE4 5PL
Forth Valley Royal Hospital Active, not recruiting
Larbert, Stirlingshire, United Kingdom, FK54WR
Fairfield General Hospital Active, not recruiting
Bury, United Kingdom, BL9 7TD
Royal Devon & Exeter NHS Foundation Trust Active, not recruiting
Exeter, United Kingdom, EX2 5DW
Queen Elizabeth University Hospital Active, not recruiting
Glasgow, United Kingdom, G51 4TF
Leeds Teaching Hospitals NHS Trust Active, not recruiting
Leeds, United Kingdom, LS1 3EX
Imperial College Healthcare Trust NHS Active, not recruiting
London, United Kingdom, W68RF
Plymouth University Active, not recruiting
Plymouth, United Kingdom, PL6 8DH
Sponsors and Collaborators
Sunovion
Investigators
Study Director: CNS Medical Director Sunovion

Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT02542696     History of Changes
Other Study ID Numbers: CTH-301
2016-000637-43 ( EudraCT Number )
First Posted: September 7, 2015    Key Record Dates
Last Update Posted: March 22, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Apomorphine
Emetics
Physiological Effects of Drugs
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action