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

NCT ID: NCT02542696

Last Updated: 2023-11-22

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

496 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-31

Study Completion Date

2022-11-08

Brief Summary

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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

Detailed Description

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Conditions

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Parkinson Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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APL-130277

APL-130277 sublingual thin film (10 mg, 15 mg, 20 mg, 25 mg, 30 mg and 35 mg)

Group Type EXPERIMENTAL

APL-130277

Intervention Type DRUG

Used to treat up to 5 "OFF" episodes per day

Interventions

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APL-130277

Used to treat up to 5 "OFF" episodes per day

Intervention Type DRUG

Other Intervention Names

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Apomorphine Hydrochloride, Sublingual Thin Film

Eligibility Criteria

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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.


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.


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.

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.


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.


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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sumitomo Pharma America, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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CNS Medical Director

Role: STUDY_DIRECTOR

Sumitomo Pharma America, Inc.

Locations

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University of Alabama Birmingham

Birmingham, Alabama, United States

Site Status

Muhammed Ali Parkinson and Movement Disorder Center/Barrow Neurological Institute

Phoenix, Arizona, United States

Site Status

Movement Disorders Center of Arizona

Scottsdale, Arizona, United States

Site Status

Clinical Trials, Inc.

Little Rock, Arkansas, United States

Site Status

The Parkinson's and Movement Disorder Institute

Fountain Valley, California, United States

Site Status

UC Irvine Health Gottschalk Medical Plaza

Irvine, California, United States

Site Status

Keck Medical Center at USC

Los Angeles, California, United States

Site Status

University of Colorado School of Medicine

Aurora, Colorado, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Parkinsons Disease and Movement Disorders Center

Boca Raton, Florida, United States

Site Status

University of Miami, Miller School of Medicine

Miami, Florida, United States

Site Status

Parkinson's Disease Treatment Center of Southwest Florida

Port Charlotte, Florida, United States

Site Status

Suncoast Neuroscience Associates Inc.

St. Petersburg, Florida, United States

Site Status

USF Parkinson's Disease and Movement Disorder Center

Tampa, Florida, United States

Site Status

Emory University Department of Neurology

Atlanta, Georgia, United States

Site Status

GRU Movement Disorders

Augusta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

NorthShore Neurological Institute B043D

Glenview, Illinois, United States

Site Status

Central DuPage Hospital - Neurodegenerative Clinic - Movement Disorders Center

Winfield, Illinois, United States

Site Status

University of Iowa Dept. of Neurology

Iowa City, Iowa, United States

Site Status

Kansas University Medical Center-Department of Neurology

Kansas City, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

University of Maryland

Baltimore, Maryland, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Michigan State University - Dept. of Neurology

East Lansing, Michigan, United States

Site Status

QUEST Research Institute

Farmington Hills, Michigan, United States

Site Status

Henry Ford Hospital

West Bloomfield, Michigan, United States

Site Status

Park Nicolet Institute - Stuthers Parkinson's Center

Golden Valley, Minnesota, United States

Site Status

SUNY Downstate Medical Center, Department of Neurology

Brooklyn, New York, United States

Site Status

Bendheim Parkinson's and Movement Disorder Center (Mount Sinai Medical Center)

New York, New York, United States

Site Status

Columbia University Medical Center - Neurological Institute, Movement Disorders

New York, New York, United States

Site Status

Duke University - Movement Disorders Clinic

Durham, North Carolina, United States

Site Status

Raleigh Neurology Associates, P.A.

Raleigh, North Carolina, United States

Site Status

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

UT Gardner-McMaster Parkinson's Center

Toledo, Ohio, United States

Site Status

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, United States

Site Status

Jefferson University Hospital Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Houston Methodist Neurological Institute

Houston, Texas, United States

Site Status

East Texas Medical Center

Tyler, Texas, United States

Site Status

University of Virginia Adult Neurology

Charlottesville, Virginia, United States

Site Status

Sentara Neuroscience Institute

Virginia Beach, Virginia, United States

Site Status

Evergreen Health

Kirkland, Washington, United States

Site Status

Swedish Neuroscience Research

Seattle, Washington, United States

Site Status

Medical University Innsbruck Neurology Department

Innsbruck, , Austria

Site Status

Wilhelminenspital Department of Neurology

Vienna, , Austria

Site Status

UHN Toronto Western Hospital

Toronto, Ontario, Canada

Site Status

Centre d'Investigation Clinique, CIC 1436, CHU Purpan

Toulouse, , France

Site Status

St. Josef-Hospital, Klinikum der Ruhr-Universitaet-Bochum, Neurologische Klinik

Bochum, , Germany

Site Status

Universitätsklinikum Ulm Neurologisches Studienzentrum im RKU

Ulm, , Germany

Site Status

Ospedali Riuniti di Ancona

Ancona, , Italy

Site Status

Centro Ricerche San Raffaele

Cassino, , Italy

Site Status

Aging Research Center, Ce.S.I. University Foundation, Chieti-Pescara Behavioural Neurology & Movement Disorders Unit

Chieti, , Italy

Site Status

IRCCS San Raffaele Pisana - Clinical Trial Center

Rome, , Italy

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital Universitari General de Catalunya

Sant Cugat Del Vallés, , Spain

Site Status

Kings College, The Maurice Wohl Neuroscience Institute

London, Greater London, United Kingdom

Site Status

Manchester University

Salford, Greater Manchester, United Kingdom

Site Status

Newcastle University

Newcastle upon Tyne, Northumberland, United Kingdom

Site Status

Forth Valley Royal Hospital

Larbert, Stirlingshire, United Kingdom

Site Status

Fairfield General Hospital

Bury, , United Kingdom

Site Status

Royal Devon & Exeter NHS Foundation Trust

Exeter, , United Kingdom

Site Status

Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Site Status

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Site Status

Imperial College Healthcare Trust NHS

London, , United Kingdom

Site Status

Plymouth University

Plymouth, , United Kingdom

Site Status

Countries

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United States Austria Canada France Germany Italy Spain United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-000637-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTH-301

Identifier Type: -

Identifier Source: org_study_id