Clincosm LogoSign in Get a demo

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

Sponsor
Sunovion (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02542696
Collaborator
(none)
226
Enrollment
70
Locations
1
Arm
86.3
Anticipated Duration (Months)
3.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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
Phase 3

Study Design

Study Type:
Interventional
Anticipated 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 :
Aug 31, 2015
Anticipated Primary Completion Date :
Nov 8, 2022
Anticipated Study Completion Date :
Nov 8, 2022

Arms and Interventions

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 Names:
  • Apomorphine Hydrochloride, Sublingual Thin Film

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Evaluation of safety and tolerability data collected, based on incidence of adverse events in the LTS phase [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. [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. [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. [Week 48]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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.

    1. 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.

    2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures.

    3. 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.

    1. 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.

    2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures.

    3. 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.

    1. 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.

    2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures.

    3. 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).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama Birmingham Birmingham Alabama United States 35233
    2 Muhammed Ali Parkinson and Movement Disorder Center/Barrow Neurological Institute Phoenix Arizona United States 85013
    3 Movement Disorders Center of Arizona Scottsdale Arizona United States 85258
    4 Clinical Trials, Inc. Little Rock Arkansas United States 72205
    5 The Parkinson's and Movement Disorder Institute Fountain Valley California United States 92708
    6 UC Irvine Health Gottschalk Medical Plaza Irvine California United States 92697
    7 Keck Medical Center at USC Los Angeles California United States 90033
    8 University of Colorado School of Medicine Aurora Colorado United States 80045
    9 MedStar Georgetown University Hospital Washington District of Columbia United States 20007
    10 Parkinsons Disease and Movement Disorders Center Boca Raton Florida United States 33486
    11 University of Miami, Miller School of Medicine Miami Florida United States 33136
    12 Parkinson's Disease Treatment Center of Southwest Florida Port Charlotte Florida United States 33980
    13 Suncoast Neuroscience Associates Inc. Saint Petersburg Florida United States 33713
    14 USF Parkinson's Disease and Movement Disorder Center Tampa Florida United States 33613
    15 Emory University Department of Neurology Atlanta Georgia United States 30329
    16 GRU Movement Disorders Augusta Georgia United States 30912
    17 Northwestern University Chicago Illinois United States 60611
    18 Rush University Medical Center Chicago Illinois United States 60612
    19 NorthShore Neurological Institute B043D Glenview Illinois United States 60026
    20 Central DuPage Hospital - Neurodegenerative Clinic - Movement Disorders Center Winfield Illinois United States 60190
    21 University of Iowa Dept. of Neurology Iowa City Iowa United States 52242
    22 Kansas University Medical Center-Department of Neurology Kansas City Kansas United States 66160
    23 University of Kentucky Lexington Kentucky United States 40536
    24 University of Maryland Baltimore Maryland United States 21201
    25 Johns Hopkins University Baltimore Maryland United States 21287
    26 Michigan State University - Dept. of Neurology East Lansing Michigan United States 48824
    27 QUEST Research Institute Farmington Hills Michigan United States 48334
    28 Henry Ford Hospital West Bloomfield Michigan United States 48322
    29 Park Nicolet Institute - Stuthers Parkinson's Center Golden Valley Minnesota United States 55427
    30 SUNY Downstate Medical Center, Department of Neurology Brooklyn New York United States 11203
    31 Bendheim Parkinson's and Movement Disorder Center (Mount Sinai Medical Center) New York New York United States 10029
    32 Columbia University Medical Center - Neurological Institute, Movement Disorders New York New York United States 10032
    33 Duke University - Movement Disorders Clinic Durham North Carolina United States 27705
    34 Raleigh Neurology Associates, P.A. Raleigh North Carolina United States 27607
    35 Wake Forest Baptist Health Winston-Salem North Carolina United States 27157
    36 University of Cincinnati Cincinnati Ohio United States 45219
    37 Cleveland Clinic Cleveland Ohio United States 44195
    38 The Ohio State University Wexner Medical Center Columbus Ohio United States 43210
    39 UT Gardner-McMaster Parkinson's Center Toledo Ohio United States 43614
    40 The Movement Disorder Clinic of Oklahoma Tulsa Oklahoma United States 74136
    41 Jefferson University Hospital Philadelphia Philadelphia Pennsylvania United States 19107
    42 Medical University of South Carolina Charleston South Carolina United States 29425
    43 Houston Methodist Neurological Institute Houston Texas United States 77030
    44 East Texas Medical Center Tyler Texas United States 75701
    45 University of Virginia Adult Neurology Charlottesville Virginia United States 322903
    46 Sentara Neuroscience Institute Virginia Beach Virginia United States 23456
    47 Evergreen Health Kirkland Washington United States 98034
    48 Swedish Neuroscience Research Seattle Washington United States 98122
    49 Medical University Innsbruck Neurology Department Innsbruck Austria A-6020
    50 Wilhelminenspital Department of Neurology Wien Austria 1160
    51 UHN Toronto Western Hospital Toronto Ontario Canada M5T 2S8
    52 Centre d'Investigation Clinique, CIC 1436, CHU Purpan Toulouse France 31059
    53 St. Josef-Hospital, Klinikum der Ruhr-Universitaet-Bochum, Neurologische Klinik Bochum Germany 44791
    54 Universitätsklinikum Ulm Neurologisches Studienzentrum im RKU Ulm Germany 89081
    55 Ospedali Riuniti di Ancona Ancona Italy 60126
    56 Centro Ricerche San Raffaele Cassino Italy 03043
    57 Aging Research Center, Ce.S.I. University Foundation, Chieti-Pescara Behavioural Neurology & Movement Disorders Unit Chieti Italy 66100
    58 IRCCS San Raffaele Pisana - Clinical Trial Center Rome Italy 00163
    59 Hospital Clinic de Barcelona Barcelona Spain 08036
    60 Hospital Universitari General de Catalunya Sant Cugat del Vallés Spain 08195
    61 Kings College, The Maurice Wohl Neuroscience Institute London Greater London United Kingdom
    62 Manchester University Salford Greater Manchester United Kingdom M68HD
    63 Newcastle University Newcastle-upon-Tyne Northumberland United Kingdom NE4 5PL
    64 Forth Valley Royal Hospital Larbert Stirlingshire United Kingdom FK54WR
    65 Fairfield General Hospital Bury United Kingdom BL9 7TD
    66 Royal Devon & Exeter NHS Foundation Trust Exeter United Kingdom EX2 5DW
    67 Queen Elizabeth University Hospital Glasgow United Kingdom G51 4TF
    68 Leeds Teaching Hospitals NHS Trust Leeds United Kingdom LS1 3EX
    69 Imperial College Healthcare Trust NHS London United Kingdom W68RF
    70 Plymouth University Plymouth United Kingdom PL6 8DH

    Sponsors and Collaborators

    • Sunovion

    Investigators

    • Study Director: CNS Medical Director, Sunovion

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sunovion
    ClinicalTrials.gov Identifier:
    NCT02542696
    Other Study ID Numbers:
    • CTH-301
    • 2016-000637-43
    First Posted:
    Sep 7, 2015
    Last Update Posted:
    Jun 9, 2022
    Last Verified:
    Jun 1, 2022
    Additional relevant MeSH terms:
    Parkinson Disease
    Apomorphine

    Study Results

    No Results Posted as of Jun 9, 2022