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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02542696
Recruitment Status : Recruiting
First Posted : September 7, 2015
Last Update Posted : November 12, 2019
Sponsor:
Information provided by (Responsible Party):
Sunovion

Brief Summary:
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

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 226 participants
Allocation: N/A
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 : March 1, 2023
Estimated Study Completion Date : March 1, 2023

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, based on incidence of adverse events in the LTS phase [ Time Frame: Throughout the entire study ]

Secondary Outcome Measures :
  1. 1. Mean change from pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) score at 15, 30, 60, and 90 minutes after dosing at Week 24, Week 36, and Week 48 visits (LTS V4, V5, and V6) of the LTS Phase. [ Time Frame: Week 48 ]
  2. 2. Percentage of subjects with a subject-rated full "ON" response within 30 minutes at Week 24, Week 36, and Week 48 visits (LTS V4, V5, and V6) of the LTS Phase. [ Time Frame: Week 48 ]
  3. 3. The percentage of instances where a full "ON" response was achieved within 30 minutes after self-administration of study medication at Week 24, Week 36, and Week 48 visits (LTS V4, V5, and V6) of the LTS Phase based on the home dosing diary entries. [ Time Frame: Week 48 ]


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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 Subjects 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. Subject 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. Subject 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;
    • 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.

De Novo Subjects 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.

Rollover Subjects 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 changes 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 subject 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.

Rollover Subjects 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 but not limited to CNS, cardiovascular, hepatic, pulmonary, metabolic, or renal 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 of an investigational product since completing a previous study using APL 130277.
  5. Development of canker or mouth sores within 14 days of completing a previous 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 subject into the study. Clinical significance to be determined by the Investigator. The eligibility of subjects who have experienced AEs related to the oral cavity during the previous study using APL-130277, should be reviewed with the medical monitor and approval obtained.
  6. Current suicidal ideation within one year of the screening visit, as evidenced by answering "yes" to Question 4 or 5 on the suicidal ideation portion of the C SSRS at Screening or attempted suicide within 5 years.

CTH-301 Completer Subjects Inclusion Criteria

  1. Completion of the CTH-301 study under protocol version 3.00, 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.

CTH-301 Completer Subjects 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 in unsafe or make treatment compliance difficult.
  3. Presence of any clinically significant medical (including but not limited to CNS, cardiovascular, hepatic, pulmonary, metabolic, or renal 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
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Contact: CNS Medical Director 1-866-503-6351

Locations
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United States, Alabama
University of Alabama Birmingham Active, not recruiting
Birmingham, Alabama, United States, 35233
United States, Arizona
Muhammed Ali Parkinson and Movement Disorder Center/Barrow Neurological Institute Active, not recruiting
Phoenix, Arizona, United States, 85013
Movement Disorders Center of Arizona Active, not recruiting
Scottsdale, Arizona, United States, 85258
Mayo Clinic Arizona Withdrawn
Scottsdale, Arizona, United States, 85259
United States, Arkansas
Clinical Trials, Inc. Completed
Little Rock, Arkansas, United States, 72205
United States, California
The Parkinson's and Movement Disorder Institute Active, not recruiting
Fountain Valley, California, United States, 92708
UC Irvine Health Gottschalk Medical Plaza Active, not recruiting
Irvine, California, United States, 92697
Keck Medical Center at USC Recruiting
Los Angeles, California, United States, 90033
Contact: Jennifer Hui    323-442-5710      
Research center of southern california Withdrawn
Oceanside, California, United States, 92056
United States, Colorado
University of Colorado School of Medicine Completed
Aurora, Colorado, United States, 80045
United States, District of Columbia
MedStar Georgetown University Hospital Active, not recruiting
Washington, District of Columbia, United States, 20007
United States, Florida
Parkinsons Disease and Movement Disorders Center Active, not recruiting
Boca Raton, Florida, United States, 33486
University of Miami, Miller School of Medicine Active, not recruiting
Miami, Florida, United States, 33136
Parkinson's Disease Treatment Center of Southwest Florida Active, not recruiting
Port Charlotte, Florida, United States, 33980
Suncoast Neuroscience Associates Inc. Active, not recruiting
Saint Petersburg, Florida, United States, 33713
USF Parkinson's Disease and Movement Disorder Center Active, not recruiting
Tampa, Florida, United States, 33613
United States, Georgia
Emory University Department of Neurology Active, not recruiting
Atlanta, Georgia, United States, 30329
GRU Movement Disorders Active, not recruiting
Augusta, Georgia, United States, 30912
United States, Illinois
Northwestern University Completed
Chicago, Illinois, United States, 60611
Rush University Medical Center Completed
Chicago, Illinois, United States, 60612
NorthShore Neurological Institute B043D Active, not recruiting
Glenview, Illinois, United States, 60026
Central DuPage Hospital - Neurodegenerative Clinic - Movement Disorders Center Completed
Winfield, Illinois, United States, 60190
United States, Iowa
University of Iowa Dept. of Neurology Completed
Iowa City, Iowa, United States, 52242
United States, Kansas
Kansas University Medical Center-Department of Neurology Active, not recruiting
Kansas City, Kansas, United States, 66160
United States, Kentucky
University of Kentucky Active, not recruiting
Lexington, Kentucky, United States, 40536
United States, Maryland
University of Maryland Completed
Baltimore, Maryland, United States, 21201
Johns Hopkins University Active, not recruiting
Baltimore, Maryland, United States, 21287
United States, Michigan
Michigan State University - Dept. of Neurology Active, not recruiting
East Lansing, Michigan, United States, 48824
QUEST Research Institute Active, not recruiting
Farmington Hills, Michigan, United States, 48334
Northern Michigan Neurology Withdrawn
Traverse City, Michigan, United States, 49684
Henry Ford Hospital Completed
West Bloomfield, Michigan, United States, 48322
United States, Minnesota
Park Nicolet Institute - Stuthers Parkinson's Center Completed
Golden Valley, Minnesota, United States, 55427
United States, New York
SUNY Downstate Medical Center, Department of Neurology Completed
Brooklyn, New York, United States, 11203
David L. Kreitzman, MD, PC Withdrawn
Commack, New York, United States, 11725
Bendheim Parkinson's and Movement Disorder Center (Mount Sinai Medical Center) Active, not recruiting
New York, New York, United States, 10029
Columbia University Medical Center - Neurological Institute, Movement Disorders Completed
New York, New York, United States, 10032
United States, North Carolina
Duke University - Movement Disorders Clinic Completed
Durham, North Carolina, United States, 27705
Raleigh Neurology Associates, P.A. Completed
Raleigh, North Carolina, United States, 27607
Wake Forest Baptist Health Active, not recruiting
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
University of Cincinnati Completed
Cincinnati, Ohio, United States, 45219
Cleveland Clinic Active, not recruiting
Cleveland, Ohio, United States, 44195
The Ohio State University Wexner Medical Center Completed
Columbus, Ohio, United States, 43210
UT Gardner-McMaster Parkinson's Center Active, not recruiting
Toledo, Ohio, United States, 43614
United States, Oklahoma
The Movement Disorder Clinic of Oklahoma Active, not recruiting
Tulsa, Oklahoma, United States, 74136
United States, Pennsylvania
Jefferson University Hospital Philadelphia Completed
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Medical University of South Carolina Active, not recruiting
Charleston, South Carolina, United States, 29425
United States, Texas
Houston Methodist Neurological Institute Active, not recruiting
Houston, Texas, United States, 77030
East Texas Medical Center Completed
Tyler, Texas, United States, 75701
United States, Virginia
University of Virginia Adult Neurology Completed
Charlottesville, Virginia, United States, 322903
Sentara Neuroscience Institute Active, not recruiting
Virginia Beach, Virginia, United States, 23456
United States, Washington
Evergreen Health Active, not recruiting
Kirkland, Washington, United States, 98034
Swedish Neuroscience Research Completed
Seattle, Washington, United States, 98122
Austria
Medical University Innsbruck Neurology Department Recruiting
Innsbruck, Austria, A-6020
Contact: Werner Poewe    00 43512504 81553      
Wilhelminenspital Department of Neurology Recruiting
Wien, Austria, 1160
Contact: Walter Pirker, MD, PhD    43 1 49150 2001      
Canada, Ontario
UHN Toronto Western Hospital Completed
Toronto, Ontario, Canada, M5T 2S8
France
Centre d'Investigation Clinique, CIC 1436, CHU Purpan Recruiting
Toulouse, France, 31059
Contact: Olivier Rascol    0033 5 61 77 22 71      
Germany
St. Josef-Hospital, Klinikum der Ruhr-Universitaet-Bochum, Neurologische Klinik Recruiting
Bochum, Germany, 44791
Contact: Siegfried Muhlack    0049 234 509 6416      
Universitätsklinikum Ulm Neurologisches Studienzentrum im RKU Recruiting
Ulm, Germany, 89081
Contact: Jan Rainer Kassubek    0049 731 177 1206      
Italy
Centro Ricerche San Raffaele Recruiting
Cassino, Italy, 03043
Contact: Maria Francesca De Pandis    0039 336 823 486      
Aging Research Center, Ce.S.I. University Foundation, Chieti-Pescara Behavioural Neurology & Movement Disorders Unit Recruiting
Chieti, Italy, 66100
Contact: Marco Onofrj    0039 0871 358525      
IRCCS San Raffaele Pisana - Clinical Trial Center Recruiting
Rome, Italy, 00163
Contact: Fabrizio Stocchi    0032 0652 252311      
Spain
Hospital Clinic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Maria Jose Marti    00 34 932272143      
Hospital Universitari General de Catalunya Recruiting
Sant Cugat del Vallés, Spain, 08195
Contact: Ernest Balaguer Martinez    0034 9356 56000      
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 Completed
Exeter, United Kingdom, EX2 5DW
Queen Elizabeth University Hospital Completed
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
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Study Director: CNS Medical Director Sunovion
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Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT02542696    
Other Study ID Numbers: CTH-301
2016-000637-43 ( EudraCT Number )
First Posted: September 7, 2015    Key Record Dates
Last Update Posted: November 12, 2019
Last Verified: November 2019
Additional relevant MeSH terms:
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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