An open label, repeat dose, dose escalation study conducted in Parkinson’s Disease patients to characterize the pharmacokinetics and effect of food on ropinirole prolonged release (PR/CR) 12mg tablets.
- Conditions
- Parkinson's diseaseMedDRA version: 9.1Level: LLTClassification code 10061536Term: Parkinson's disease
- Registration Number
- EUCTR2006-006209-94-DE
- Lead Sponsor
- GlaxoSmithKline Research & Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 36
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).
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To demonstrate dose proportionality for ropinirole using an extended release<br>(PR/CR) formulation of ropinirole over the dose range 4-12mg when<br>administered to patients with a diagnosis of idiopathic Parkinson’s Disease.<br>• To determine the effect of food administered as a high fat breakfast on the<br>absorption of ropinirole PR/CR at 12mg (highest tablet strength).<br>• To determine dosage strength equivalence for ropinirole PR/CR administered as<br>1x12mg tablet compared with 3x4mg tablets.;Secondary Objective: To further confirm the safety and tolerability of ropinirole PR/CR over a dose<br>range of 2 - 12 mg when administered to patients with a diagnosis of idiopathic<br>Parkinson’s Disease.;Primary end point(s): • Ropinirole AUC (0-24ss), the area under the steady-state plasma concentration time curve over the dosing interval<br>• Ropinirole Cmaxss: the maximum observed steady-state plasma concentration
- Secondary Outcome Measures
Name Time Method