| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10061536 |
| E.1.2 | Term | Parkinson's disease |
|
| 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 demonstrate dose proportionality for ropinirole using an extended release
(PR/CR) formulation of ropinirole over the dose range 4-12mg when
administered to patients with a diagnosis of idiopathic Parkinson’s Disease.
• To determine the effect of food administered as a high fat breakfast on the
absorption of ropinirole PR/CR at 12mg (highest tablet strength).
• To determine dosage strength equivalence for ropinirole PR/CR administered as
1x12mg tablet compared with 3x4mg tablets. |
|
| E.2.2 | Secondary objectives of the trial |
To further confirm the safety and tolerability of ropinirole PR/CR over a dose
range of 2 - 12 mg when administered to patients with a diagnosis of idiopathic
Parkinson’s Disease. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female patients aged between 30 and 85 years of age inclusive at
screening.
2. Body mass index of 18 to 32 kg/m2, with a body weight of at least 50 kg.
3. Diagnosis of idiopathic Parkinson’s Disease graded according to modified Hoehn
& Yahr Stage I-III (Appendix 4).
4. Patients must have provided written informed consent prior to performing any
Screening assessments, including any washout of concomitant medications in
preparation for this study.
5. QTc interval of < 450ms at screening (or QTc < 480ms in patients with Bundle
Branch Block). |
|
| E.4 | Principal exclusion criteria |
1. Patients who have an abnormality on physical examination. A patient with clinical
abnormality may be included only if the Investigator considers that the abnormality
will not introduce additional risk factors and will not interfere with the study
procedures.
2. Patients who, in the opinion of the Investigator, have medical conditions which could present a safety concern. These may include, but are not limited to, the following disorders: diabetes, peripheral neuropathy, rheumatoid arthritis, fibromyalgia syndrome, symptomatic orthostatic hypotension, hepatic or renal failure, pleuropulmonary fibrosis, significant and/or uncontrolled psychiatric, haematological, endocrinological, neurological (other than Parkinson’s disease), or cardiovascular disease (including myocardial infarction, unstable angina pectoris, cardiac arrhythmias, cerebrovascular accident (CVA), or patients who are known to have malignancy, are being treated for malignancy or have had treatment for malignancy within the last year (other than basal cell cancer).
3. Patients having a clinically significant abnormal laboratory value, ECG, or physical
examination findings not resolved by the time of the baseline examinations.
Abnormal 12-lead ECG findings include, but are not limited to, the following:
myocardial ischemia, clinically significant conduction abnormalities, or clinically
significant arrhythmias.
4. Positive result for Hepatitis B surface antigen, Hepatitis C antibody or Human
Immunodeficiency Virus (HIV) antibody at screening.
5. Positive alcohol test result and / or urine test for undeclared drugs at screening.
6. Recent history of moderate to severe dizziness, syncope, or orthostatic hypotension,
defined as a fall in blood pressure, after rising from the supine to erect posture, of >
30 mmHg for systolic pressure and > 20 mmHg for diastolic pressure.
7. Significant sleep disorder or Epworth Sleep Score (Appendix 5) ≥ 9 at screening.
8. Patients with a lying/sitting diastolic blood pressure ≥110mmHg or ≤50mmHg or a
systolic blood pressure ≥180mmHg or ≤90mmHg at the Screening or Baseline Visit.
9. History of any dopaminergic treatment (other than ropinirole IR and L-dopa) within
2 weeks prior to first dose.
• Patients on dopaminergic agonists other than ropinirole IR and L-dopa may be
enrolled if the agent is stopped for a 2-week wash-out period prior to first dose.
• Patients taking ropinirole IR or L-dopa may switch to ropinirole PR/CR 2mg on
study day 1, providing they have first followed the manufacturer’s down
titration guidelines.
• Patients taking ropinirole IR > 4mg/day must be down-titrated according to the
manufacturer’s guidelines prior to study day 1.
• Patients taking ropinirole IR or L-dopa must have been on a stable dose for at
least 4 weeks prior to screening; doses of ropinirole IR or L-dopa may need to
be adjusted prior to or during the study.
• Patients on selegiline, amantadine, or anticholinergics may be enrolled but must
have been on a stable dose for at least one month prior to study enrolment and
must remain on their current dose throughout the treatment phase of the study.
10. Withdrawal, introduction, or change in dose of hormone replacement therapy and/or any drug known to substantially inhibit CYP1A2 (e.g., cimetidine, ciprofloxacin,
fluvoxamine) or induce CYP1A2 (e.g., tobacco, or omeprazole) within 7 days prior
to study enrolment. Patients already on these agents may be enrolled but must
remain on stable doses of the agent for at least one month prior to enrolment and
throughout the treatment phase of the study.
11. Patients who smoke >20 cigarettes per day and will not maintain a constant smoking habit for the duration of the study.
12. Blood donation or significant blood loss less than 90 days before Day 1 of the
current study.
13. Definite or suspected personal history, or family history, of adverse reactions or
hypersensitivity to ropinirole or to drugs with a similar chemical structure.
14. Use of any investigational drug (with the exception of ropinirole PR/CR) within 30
days or 5 half-lives (whichever is longer) before the start of dosing with study
medication.ROP109087
15. Patients who have received over-the-counter (OTC) medicine within 48 h before the first dose of study drug. Patients who have taken OTC medication may still be
entered in the study, if in the opinion of the Investigator, the medication received
will not interfere with the study procedures or compromise safety.
16. Recent history, or suspicion, of drug dependence or abuse of alcohol (with alcohol
abuse defined as an average weekly intake of greater than 21 units or an average
daily intake of greater than 3 units for men; greater than 14 units per week or greater than 2 units per day for women. One unit is equivalent to half a pint of beer, one measure of spirits, or one glass of wine).
Please see the protocol for the remaining exclusion criteria |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• Ropinirole AUC (0-24ss), the area under the steady-state plasma concentration time curve over the dosing interval
• Ropinirole Cmaxss: the maximum observed steady-state plasma concentration |
|
| 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 | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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 | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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