Safety, tolerability and efficacy study to examine APL-130277 in patients with Parkinson’s Disease.

• Register: EUCTR
• Last refreshed on: 14 March 2022
• Main ID: EUCTR2016-000637-43-AT
• Date of registration: 15/12/2017
• Prospective Registration: Yes
• Primary sponsor: Sunovion Pharmaceuticals Inc.
• Public title: Safety, tolerability and efficacy study to examine APL-130277 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: 01/02/2018
• Target sample size: 450
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000637-43
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Susan Honn
• Affiliation: Syneos Health LLC

• Name: Susan Honn
• Affiliation: Syneos Health LLC

Key inclusion & exclusion criteria

Inclusion criteria:
1. Completion of Study 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 Study 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 207
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 243

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 within 14 days of completing Study CTH-302.
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 followup 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 the Screening or attempted suicide within 5 years.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

"Levodopa Responsive Patients with Parkinson’s Disease complicated by Motor Fluctuations (“OFF” Episodes)"
MedDRA version: 22.1 Level: LLT Classification code 10034006 Term: Parkinson's disease aggravated System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Apomorphine hydrochloride
Product Code: APL-130277
Pharmaceutical Form: Sublingual film
INN or Proposed INN: Apomorphine hydrochloride
CAS Number: 41372-20-7
Current Sponsor code: APL-130277
Other descriptive name: APOMORPHINE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10 -
Pharmaceutical form of the placebo: Sublingual film
Route of administration of the placebo: Sublingual use

Product Name: Apomorphine hydrochloride
Product Code: APL-130277
Pharmaceutical Form: Sublingual film
INN or Proposed INN: Apomorphine hydrochloride
CAS Number: 41372-20-7
Current Sponsor code: APL-130277
Other descriptive name: APOMORPHINE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Sublingual film
Route of administration of the placebo: Sublingual use

Product Name: Apomorphine hydrochloride
Product Code: APL-130277
Pharmaceutical Form: Sublingual film
INN or Proposed INN: Apomorphine hydrochloride
CAS Number: 41372-20-7
Current Sponsor code: APL-130277
Other descriptive name: APOMORPHINE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Sublingual film
Route of administration of the placebo: Sublingual use

Product Name: Apomorphine hydrochloride
Product Code: APL-130277
Pharmaceutical Form: Sublingual film
INN or Proposed INN: Apomorphine hydrochloride
CAS Number: 41372-20-7
Current Sponsor code: APL-130277
Other descriptive name: APOMORPHINE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Sublingual film
Route of administration of the placebo: Sublingu

Primary Outcome(s)

Secondary Objective: "Not applicable"

Timepoint(s) of evaluation of this end point: During all the LTS phase.

Main Objective: To evaluate the long-term safety and tolerability of APL-130277 in patients with Parkinson’s disease (PD).

Primary end point(s): Evaluation of safety and tolerability data collected, based on incidence of adverse events in the LTS Phase.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Mean change from pre-dose in MDS-UPDRS MOTOR at Weeks 24, 36, 48 visits.
2. Percentage of subjects with a subject-rated full "ON" response within 30 minutes at Weeks 24, 36, 48 visits.
3. Percentage of instances where a full "ON" response within 30 minutes after self-administration of study medication at Weeks 24, 36, 48 visits of the LTS Phase
4. CGI-I post dosing
5. PGI-I post dosing
6. PDQ-39.
7. MDS-UPDRS – Part II.
8. Percentage of subjects with Investigator-rated full "ON" response within 30 minutes during the titration period.
Other Patient-Reported Secondary Endpoints
9. Change from baseline in the Epworth Sleepiness Scale (ESS)
Safety Endpoints
1. 12 lead ECGs
2 Incidences of oropharyngeal and dopaminergic AEs,
3 C-SSRS, QUIP RS both

Secondary end point(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.
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.
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.
4. CGI-I post dosing.
5. PGI-I post dosing.
6. Change from baseline in the PDQ-39.
7. Change from baseline in the MDS-UPDRS – Part II: Motor Aspects of Experiences of Daily Living.
8. Percentage of subjects with Investigator-rated full "ON" response within 30 minutes during the titration period.
9. Change from baseline in the Epworth Sleepiness Scale (ESS)
Safety Endpoints
1. Observed values and Change in 12 lead ECGs
2 Incidences of oropharyngeal and dopaminergic AEs,
3 C-SSRS, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP RS)

Secondary ID(s)

CTH-301

NCT02542696

2016-000637-43-GB

Source(s) of Monetary Support

Sunovion Inc

Ethics review

Status: Approved
Approval date: 01/02/2018
Contact: