A fixed dose, dose response study for ropinirole prolonged release (PR) in patients with early stage Parkinson’s Disease.

• Register: EUCTR
• Last refreshed on: 6 January 2015
• Main ID: EUCTR2011-002827-17-EE
• Date of registration: 08/02/2013
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Limited
• Public title: A fixed dose, dose response study for ropinirole prolonged release (PR) in patients with early stage Parkinson’s Disease.
• Scientific title: A fixed dose, dose response study for ropinirole prolonged release (PR) in patients with early stage Parkinson’s Disease.
• Date of first enrolment: 23/04/2013
• Target sample size: 210
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002827-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Alternative dose of the same IMP. Number of treatment arms in the trial: 6

Countries of recruitment

Estonia, Korea, Republic of, Russian Federation, Slovakia, United States

Contacts

• Name: GSK Clinical Support Helpdesk
• Affiliation: GlaxoSmithKline

• Name: GSK Clinical Support Helpdesk
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for enrolment in the study must meet all of the following criteria:

1. Diagnosis of idiopathic Parkinson’s disease (according to modified Hoehn & Yahr criteria Stages I-III.)
2. Subjects aged 30 years or greater at screening. Women of child-bearing potential must be practicing a clinically accepted method of contraception during the study and for at least one month prior to randomization and one month following completion of the study. Acceptable contraceptive methods include abstinence, oral contraception, injectable progestogen, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, surgical sterilisation, male partner sterilization, intrauterine device [IUD], or double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository.
3. A baseline UPDRS motor score of at least 10.
4. Limited prior exposure to low or moderate doses of L-DOPA (up to 3 months in total) or dopamine agonists including ropinirole (up to 6 months in total) is allowed provided treatment is discontinued for a minimum of 4 weeks prior to screening.
5. Provide written informed consent for this study.
6. Be willing and able to comply with study procedures.

Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the GSK investigational product or other study treatment that may impact subject eligibility is provided in the Investigator Brochure and product label.

Deviations from inclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.

French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
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 148
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 62

Exclusion criteria:
Subjects meeting any of the following criteria must not be enrolled in the study:

1. Subjects with Parkinson’s disease in whom dopaminergic therapy is not warranted at the time of enrolment (screening).
2. Subjects with severe, clinically significant condition(s) other than Parkinson’s disease which, in the opinion of the investigator, would render the subject unsuitable for the study (e.g., psychiatric, haematological, renal, hepatic, endocrinology, neurological [other than Parkinson’s disease], cardiovascular, or active malignancy [other than basal cell carcinoma]).
3. Subjects with crippling degenerative arthritis or other physical or mental conditions which would preclude accurate assessment of efficacy or safety.
4. Subjects with prior or current major psychosis (e.g., schizophrenia or psychotic depression) e.g. scoring 3 or 4 on UPDRS item 2 [thought disorder] or item 3 [depression].
5. Subjects with severe clinical dementia e.g. scoring 3 or 4 on UPDRS item 1 [mentation].
6. Subjects with severe dizziness or fainting due to postural hypotension on standing.
7. Subjects with a personal history of melanoma.
8. Subjects with clinically significant abnormalities in laboratory or ECG tests at Screening. If findings are outside the normal range and the subject is included, it must be documented by the investigator that the findings are not of clinical significance.
9. Subjects who are diagnosed with an impulse control disorder. The modified MIDI will be conducted at screening. Subjects who score positive for this screen must be referred to a specialist for diagnostic evaluation prior to enrolling (screening) in the study.
10. Subjects who have an active suicidal plan/intent or have had active suicidal thoughts in the past 6 months. Subjects who have a history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt.
11. Current alcohol or drug dependence.
12. Definite or suspected personal or family history of clinically significant adverse reactions or hypersensitivity to ropinirole (or to drugs with a similar chemical structure) that would preclude long-term dosing with ropinirole.
13. Withdrawal, introduction, or change in dose of hormone replacement therapy and/or any drug known to substantially inhibit CYP1A2 (e.g. ciprofloxacine, fluvoxamine, cimetidine, ethinyloestradiol) or induce CYP1A2 (e.g. tobacco, omeprazole) within 7 days prior to baseline (randomization).
14. Subjects already on chronic therapy with any of these agents may be enrolled but doses must have remained stable from 7 days prior to baseline (randomization) through the end of the treatment period. Smokers should maintain their normal smoking habit.
15. Women who are pregnant or breast-feeding.
16. Use of an investigational drug from 30 days or 5 half-lives (which ever is longer) prior to baseline (randomization) through to the end of the treatment period.

Deviations from exclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.


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

Health Condition(s) or Problem(s) studied

Early stage Parkinson's Disease.
MedDRA version: 14.1 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

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

Intervention(s)

Trade Name: REQUIP-MODUTAB , 2mg
Product Name: ropinirole PR, 2mg
Product Code: SK&F101468
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: ROPINIROLE
CAS Number: 91374-21-9
Current Sponsor code: SK&F101468
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Prolonged-release tablet
Route of administration of the placebo: Oral use

Trade Name: REQUIP-MODUTAB , 4mg
Product Name: ropinirole PR, 2mg
Product Code: SK&F101468
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: ROPINIROLE
CAS Number: 91374-21-9
Current Sponsor code: SK&F101468
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Prolonged-release tablet
Route of administration of the placebo: Oral use

Trade Name: REQUIP-MODUTAB , 8mg
Product Name: ropinirole PR
Product Code: SK&F101468
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: ROPINIROLE
CAS Number: 91374-21-9
Current Sponsor code: SK&F101468
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 8-
Pharmaceutical form of the placebo: Prolonged-release tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To investigate the tolerability of fixed doses of ropinirole PR as monotherapy in patients with early stage Parkinson’s disease.

Timepoint(s) of evaluation of this end point: Week 4 of the Maintenance period.

Main Objective: To characterize the dose response of fixed doses of ropinirole PR as monotherapy in patients with early stage Parkinson’s disease.

Primary end point(s): Change from baseline in UPDRS motor score at Week 4 of the Maintenance period.

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints include:

• Percentage of patients with a = 5 point reduction from baseline in UPDRS motor score at Week 4 of the Maintenance Period.
• Percentage of patients with a = 10 point reduction from baseline in UPDRS motor score at Week 4 of the Maintenance Period.
• Percentage of patients with a = 10 point reduction from baseline in the UPDRS parts II and III combined at Week 4 of the Maintenance Period.
• Responder defined as patients with a =30% reduction in baseline UPDRS motor score at Week 4 of the Maintenance Period
• Change from baseline in the UPDRS parts II and III combined at Week 4 of the Maintenance Period
• Change from baseline in UPDRS Activities of Daily Living at Week 4 of the Maintenance Period
• Change from baseline in the total UPDRS score (parts I-III) at Week 4 of the Maintenance Period
• Change from baseline in the UPDRS part I (mentation) at week 4 of the Maintenance Period
• Responder defined as patients with a score of much improved or very much improved on the Clinical Global Impression – Global Improvement (CGI-I) scale at Week 4 of the Maintenance Period
• Percentage of subjects withdrawn from the study due to lack of efficacy.

Timepoint(s) of evaluation of this end point: All endpoints will be evaluated at week 4 of the Maintenance period with the exception of the percentage of subjects withdrawn from the study due to lack of efficacy.

Secondary ID(s)

ROP111662

Source(s) of Monetary Support

GlaxoSmithKline Research & Development Limited