E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language |
|
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 | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10034005 |
E.1.2 | Term | Parkinson's disease and parkinsonism |
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 determine the long-term safety and tolerability of AP-CD/LD in
subjects with advanced PD who completed the core study IN 11 004. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective to determine the long-term clinical benefit of
AP-CD/LD in subjects with advanced PD who completed the core study
IN 11 004. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients who successfully completed the core study IN 11 004 and,
in the opinion of the Investigator would benefit from long-term
treatment with AP-CD/LD
2.Continue to carry the diagnosis of Parkinson's disease consistent with
UK brain bank criteria.
3. Patients who have a good response to levodopa in the opinion of the
investigator
4. Patients able and willing to give written (signed and dated) informed
consent to participate in the study |
|
E.4 | Principal exclusion criteria |
1. Participation in a clinical trial other than study IN 11 004 and receipt
of an investigational medication other than those administered in study
IN 11 004, within 28 days prior to the planned start of treatment
2. Previous or planned functional neurosurgical or Duodopa treatment
for Parkinson's Disease (e.g., procedures including ablation or deep
brain stimulation)
3. Non-selective monoamine oxidase (MAO) inhibitors within 28 days
prior to Baseline Visit or planned administration during study
participation.
4. If, in the opinion of the Investigator, patient should not participate in
the study
5. Women who are pregnant or nursing. Women of childbearing potential
who are not willing to use a medically acceptable method of
contraception. Medically acceptable methods of contraception that may
be used by the patient and /or partner include: True abstinence when
this is in line with the preferred and usual lifestyle of the patient, oral
contraceptive agents, intrauterine devices (IUDs), implantable
contraceptives (e.g., Norplant), transdermal hormonal contraceptives
(e.g., Ortho-Evra), and injectable contraceptives (e.g., Depo-Provera),
condom and /or diaphragm, diaphragm with vaginal spermicide, surgical
sterilization (6 months), or postmenopausal females (no menstrual
period for > 2years) or vasectomy ( > 6 months) . The current
contraceptive therapy must be maintained through the end of the study
(End of study visit or final follow-up phone visit, whichever is later).
Hormonal contraceptive therapy must be a stable dose for at least 90
days prior to first study drug administration. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety measures:
1. Adverse Events
2. Specific evaluation of GI complaints (Adverse events of special
interest)
3. Withdrawal rates, days and reason to withdrawals
4. Safety laboratory (hematology, biochemistry, Vitamin B12, Folic Acid
and urinalysis)
5. Vital signs
6. Electrocardiogram (ECG)
7. Physical examination
8. Orthostatic hypotension evaluation
9. Evaluation of suicidality using the Columbia Suicide Severity Rating
Scale (C-SSRS) baseline (Visit 1) to EOS (Visit 7) visit
10. Assessment of impulse control using the Questionnaire for
Impulsive-Compulsive Disorders in Parkinson's Disease–Rating Scale
(QUIP-RS)
11. Change from baseline (Visit 1) to EOS (Visit 7) visit in the Scales for
Outcomes in Parkinson's Disease - Epworth Sleepiness Scale (ESS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Efficacy Outcome Measures: The following efficacy endpoints are predefined as secondary endpoints for approximately the first 150 enrolled patients.
1. Change from Baseline to EOS in the percentage and total hours of
daily "Off time" during waking hours based on Hauser Home Diary
assessments; Total number of "Off " hours normalized to a 16- hour
waking day will also be calculated but only a single p-value applicable to
both the percentage and hours will be reported.
2. Change from Baseline to EOS in "On time" without troublesome
dyskinesia during waking hours
3. Change from Baseline to EOS in the number of daily Levodopa doses
4. CGI-I at EOS as recorded by physician (all enrolled patients)
5. CGI-I at EOS as recorded by patient (all enrolled patients)
6. Change from Baseline in total UPDRS Score (Sum of Parts I-III)
7. Change from Baseline to EOS in UPDRS Part II (Activities of Daily
8. Change from Baseline to EOS in UPDRS Motor Examination (part III -
evaluated 2-3 hours after last LD dose)
9. Change from Baseline to EOS in PDQ-39 summary index
10. Change from Baseline to EOS in troublesome dyskinesia
11. Change from Baseline to EOS in "On time" without dyskinesia
during waking hours.
In addition, the following exploratory efficacy endpoints will be
XML File Identifier: U296PMl90KM+gupepZuvXFV3YQw=
Page 16/27
evaluated.
• Change from Baseline to EOS in the Parkinson's Disease Sleep Scale
(PDSS-2)
• Change from Baseline to EOS (hours during waking time) for each
diary category not listed as secondary endpoint
• Change from Baseline to EOS in the Freezing of Gait
• Change from Baseline to EOS in Morning Akinesia
• Change from Baseline to EOS of percentage of time during waking
hours of each diary category excluding sleep time and "Off time"
• Change from Baseline to EOS in UPDRS part IV, evaluated as
dyskinesia sum score (sum of items 32-35) and wearing-off sum score
(sum of items 36-39). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
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 | No |
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.8.3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Bulgaria |
Germany |
Hungary |
Israel |
Italy |
Poland |
Slovakia |
Spain |
Ukraine |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 6 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 6 |