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

• Register: ClinicalTrials.gov
• Last refreshed on: 21 November 2022
• Main ID: NCT02542696
• Date of registration: 03/09/2015
• Prospective Registration: No
• Primary sponsor: Sunovion
• Public title: 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
• Scientific 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)
• Date of first enrolment: August 31, 2015
• Target sample size: 427
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02542696
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Austria, Canada, France, Germany, Italy, Spain, United Kingdom, United States

Contacts

• Name: CNS Medical Director
• Affiliation: Sunovion

Key inclusion & exclusion 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 birt


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson Disease

Intervention(s)

Drug: APL-130277

Primary Outcome(s)

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(s)

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]

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]

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]

Secondary ID(s)

CTH-301

2016-000637-43

Source(s) of Monetary Support

Please refer to primary and secondary sponsors