| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
"Levodopa Responsive Patients with Parkinson’s Disease complicated by Motor Fluctuations
(“OFF” Episodes)"
|
|
| E.1.1.1 | Medical condition in easily understood language |
Central nervous system disease affecting the movement complicated by off symptoms.
|
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 22.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10034006 |
| E.1.2 | Term | Parkinson's disease aggravated |
| E.1.2 | System Organ Class | 100000004852 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the long-term safety and tolerability of APL-130277 in patients with Parkinson’s disease (PD). |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. |
|
| E.4 | Principal 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Evaluation of safety and tolerability data collected, based on incidence of adverse events in the LTS Phase. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| During all the LTS phase. |
|
| E.5.2 | 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) |
|
| E.5.2.1 | 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 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| United States |
| Austria |
| France |
| Germany |
| Italy |
| Spain |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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