A Fixed Dose Study of Ropinirole Prolonged Release as Adjunctive Treatment in Patients With Advanced Parkinson's Disease

NCT ID: NCT01494532

Last Updated: 2018-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 352 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-02
• Study Completion Date: 2014-11-18

Brief Summary

This is a double blind, fixed dose, parallel group study to characterize the dose response of ropinirole PR as adjunctive therapy to L-dopa in patients with late stage Parkinson's disease. The primary endpoint of this study, mean change from baseline in total awake time spent "off' is the same endpoint as used in the ropinirole PR pivotal study for advanced Parkinson's disease patients. This study includes a wide range of ropinirole doses (4-24mg) with the 8mg, 12mg, and 16mg per day doses powered to detect a 1.7 hour difference in total awake time spent "off" compared with placebo. The dose of Ldopa will remain stable through the study, unless the subject experiences tolerability issues that require an L-dopa dose reduction. Up to three L-dopa dose reductions are allowed, making a total reduction of up to approximately 30%. Keeping the L-dopa dose constant where possible is important to avoid confounding the efficacy data. Clinical review of the primary and secondary endpoints will be performed in order to establish the lowest maximally effective therapeutic dose.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

ropinirole

active treatment 4, 8, 12, 16, or 24mg/day

Group Type: EXPERIMENTAL

ropinirole/L-dopa

Intervention Type: DRUG

Ropinirole as adjunctive therapy with L-dopa

placebo

placebo comparator 4, 8, 12, 16, or 24mg/day

Group Type: PLACEBO_COMPARATOR

placebo/L-dopa

Intervention Type: DRUG

Placebo as adjunctive therapy with L-dopa

Interventions

ropinirole/L-dopa

Ropinirole as adjunctive therapy with L-dopa

Intervention Type: DRUG

placebo/L-dopa

Placebo as adjunctive therapy with L-dopa

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of idiopathic Parkinson's disease (according to modified Hoehn & Yahr criteria Stages II-IV) and demonstrating lack of control with L-dopa therapy (e.g.

end of dose akinesia, simple on/off fluctuations).

• Subjects receiving a stable dose of L-dopa for at least 4 weeks prior to screening.
• A minimum of 3 hours awake "off-time" for each diary day recorded during the baseline period.
• Men or non-pregnant/non-breast-feeding women of at least 30 years of age 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.
• Provide written informed consent for this study.
• Be willing and able to comply with study procedures, including diary card completion and follow-up clinic visits.

Exclusion Criteria

• Late stage advanced subjects demonstrating incapacitating peak dose or diphasic dyskinesia on their stable dose of L-dopa
• Consumption of any dopamine agonist, including ropinirole, within four weeks of randomization in the study.
• 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]).
• Subjects with crippling degenerative arthritis or other physical or mental conditions which would preclude accurate assessment of efficacy or safety.
• 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].
• Subjects with severe clinical dementia e.g. scoring 3 or 4 on UPDRS item 1 [mentation].
• Subjects with severe dizziness or fainting due to postural hypotension on standing.
• Subjects with a personal history of melanoma.
• 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.
• 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.
• 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.
• Current alcohol or drug dependence.
• 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.
• 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 enrolment (randomization). Subjects already on chronic therapy with any of these agents may be enrolled but doses must have remained stable from 7 days prior to enrolment (randomization) through the end of the treatment period.
• Women who are pregnant or breast-feeding.
• Use of an investigational drug from 30 days or 5 half-lives (whichever is longer) prior to enrolment (randomization) through to the end of the treatment period. 15. Women who are pregnant or breast-feeding. 16. Use of an investigational drug from 30 days or 5 half-lives (whichever is longer) prior to enrolment (randomization) through to the end of the treatment period.

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Fountain Valley, California, United States

GSK Investigational Site

Pasadena, California, United States

GSK Investigational Site

Reseda, California, United States

GSK Investigational Site

Ventura, California, United States

GSK Investigational Site

Boca Raton, Florida, United States

GSK Investigational Site

Tampa, Florida, United States

GSK Investigational Site

Springfield, Massachusetts, United States

GSK Investigational Site

Forest Hills, New York, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

San Martín, Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Caba, , Argentina

GSK Investigational Site

Valdivia, Los Lagos Region, Chile

GSK Investigational Site

Viña del Mar, Región de Valparaíso, Chile

GSK Investigational Site

Santiago, , Chile

GSK Investigational Site

Santiago, , Chile

GSK Investigational Site

Santiago, , Chile

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Chelyabinsk, , Russia

GSK Investigational Site

Kazan', , Russia

GSK Investigational Site

Krasnoyarsk, , Russia

GSK Investigational Site

Kursk, , Russia

GSK Investigational Site

Novosibirsk, , Russia

GSK Investigational Site

Omsk, , Russia

GSK Investigational Site

Perm, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saratov, , Russia

GSK Investigational Site

Smolensk, , Russia

GSK Investigational Site

Ufa, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Yekaterinburg, , Russia

GSK Investigational Site

Banská Bystrica, , Slovakia

GSK Investigational Site

Bratislava, , Slovakia

GSK Investigational Site

Bratislava, , Slovakia

GSK Investigational Site

Bratislava, , Slovakia

GSK Investigational Site

Bratislava, , Slovakia

GSK Investigational Site

Dubnica nad Váhom, , Slovakia

GSK Investigational Site

Trnava, , Slovakia

GSK Investigational Site

Anyang-si, , South Korea

GSK Investigational Site

Busan, , South Korea

GSK Investigational Site

Daejeon, , South Korea

GSK Investigational Site

Seongnam-si Gyeonggi-do, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Sungnam, , South Korea

Countries

United States; Argentina; Chile; Estonia; Russia; Slovakia; South Korea

Study Documents

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

111569

Identifier Type: -

Identifier Source: org_study_id