A Fixed Dose, Dose Response Study for Ropinirole Prolonged Release in Patients With Early Stage Parkinson's Disease

NCT01485172 | Completed Phase 4 Results

• 1 other identifier: 111662
• Study Type: interventional
• Target: 186
• Locations: 5 countries
• Sites: 34

Brief Summary

This study is a fixed dose, dose response study to characterize the dose response for ropinirole PR in early stage PD patients (Hoehn \& Yahr stages I-III). After screening and baseline assessments, subjects will be randomized to one of six final target treatment groups (placebo, 2, 4, 8, 12 or 24mg/day ropinirole PR). The study will consist of a screening period, an up-titration period, a maintenance period, a down titration period and a follow up period. This study utilizes change from baseline in the UPDRS motor score as the primary endpoint, in line with that used in the ropinirole PR monotherapy pivotal study (SK\&F101468/168). Clinical review of the primary and secondary endpoints will be performed in order to establish the lowest maximally effective therapeutic dose.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline (BL) in Unified Parkinson Disease (PD) Rating Scale (UPDRS) Motor Score

  The UPDRS is a clinician based rating scale used to measure motor impairments and disability. The UPDRS assesses six features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the participant. One of the six features include the Part III - Motor Examination where scores can range 0-108 where the maximum score indicates the worse condition. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the individual post-randomization values. The least squares(LS) means were estimated using the mixed model repeated measures(MMRM) adjusting for BL UPDRS motor score and race(white versus other) or by using the non-parametric rank analysis of covariance(ANCOVA).

  Baseline and Week 4 of the Maintenance Period (Study Week 17)

Secondary Outcomes (10)

• Number of Participants With a >=5 Points Reduction From Baseline in UPDRS Motor Score

  Baseline and Week 4 of the Maintenance Period (Study Week 17)

• Number of Participants With a >=10 Points Reduction From Baseline in UPDRS Motor Score

  Baseline and Week 4 of the Maintenance Period (Study Week 17)

• Number of Participants With a >=10 Points Reduction From Baseline in UPDRS Parts II and III Combined

  Baseline and Week 4 of the Maintenance Period (Study Week 17)

• Responder Rate Defined as Participants With a >=30% Reduction in Baseline UPDRS Motor Score

  Baseline and Week 4 of the Maintenance Period (Study Week 17)

• Change From Baseline in UPDRS Parts II and III Combined

  Baseline and Week 4 of the Maintenance Period (Study Week 17)

Study Arms (2)

ropinirole

EXPERIMENTAL

ropinirole 2, 4, 8, 12, or 24 mg/day

Drug: ropinirole monotherapy

placebo

PLACEBO COMPARATOR

placebo comparator 2, 4, 8, 12, or 24 mg/day

Drug: ropinirole monotherapy; Drug: placebo monotherapy

Interventions

ropinirole monotherapy DRUG

ropinirole as monotherapy in Parkinson's disease

placebo; ropinirole

placebo monotherapy DRUG

placebo as monotherapy in Parkinson's disease

placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of idiopathic Parkinson's disease (according to modified Hoehn \& Yahr criteria Stages I-III.)
• 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.
• A baseline UPDRS motor score of at least 10.
• 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.
• Provide written informed consent for this study.
• Be willing and able to comply with study procedures.

You may not qualify if:

• Subjects with Parkinson's disease in whom dopaminergic therapy is not warranted at the time of screening.
• Subjects with severe, clinically significant condition(s) other than Parkinson's disease which, in the opinion of the investigator, 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 precluding 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 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.
• Subjects with an active suicidal plan/intent or have had active suicidal thoughts in the past 6 months. Subjects with 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 baseline (randomization).
• Subjects 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 normal smoking habit.
• Women who are pregnant or breast-feeding.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (34)

GSK Investigational Site

Fountain Valley, California, 92708, United States

Location

GSK Investigational Site

Pasadena, California, 91105, United States

Location

GSK Investigational Site

Reseda, California, 91355, United States

Location

GSK Investigational Site

Torrance, California, 90505, United States

Location

GSK Investigational Site

Ventura, California, 93003, United States

Location

GSK Investigational Site

Boca Raton, Florida, 33486, United States

Location

GSK Investigational Site

Tampa, Florida, 33612, United States

Location

GSK Investigational Site

Augusta, Georgia, 30912, United States

Location

GSK Investigational Site

Forest Hills, New York, 11375, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45227, United States

Location

GSK Investigational Site

Richmond, Virginia, 23249, United States

Location

GSK Investigational Site

Tallinn, 10138, Estonia

Location

GSK Investigational Site

Tallinn, 13419, Estonia

Location

GSK Investigational Site

Tartu, 51014, Estonia

Location

GSK Investigational Site

Chelyabinsk, 454136, Russia

Location

GSK Investigational Site

Kazan', 420012, Russia

Location

GSK Investigational Site

Krasnoyarsk, 660022, Russia

Location

GSK Investigational Site

Kursk, 305007, Russia

Location

GSK Investigational Site

Novosibirsk, 630091, Russia

Location

GSK Investigational Site

Omsk, 644033, Russia

Location

GSK Investigational Site

Perm, 614990, Russia

Location

GSK Investigational Site

Saint Petersburg, 194044, Russia

Location

GSK Investigational Site

Saratov, 410012, Russia

Location

GSK Investigational Site

Smolensk, 214019, Russia

Location

GSK Investigational Site

Ufa, 450000, Russia

Location

GSK Investigational Site

Yekaterinburg, 620102, Russia

Location

GSK Investigational Site

Banská Bystrica, 974 04, Slovakia

Location

GSK Investigational Site

Bratislava, 813 69, Slovakia

Location

GSK Investigational Site

Bratislava, 831 03, Slovakia

Location

GSK Investigational Site

Busan, 602-715, South Korea

Location

GSK Investigational Site

Donggu Gwangju, 501757, South Korea

Location

GSK Investigational Site

Seoul, 138-736, South Korea

Location

GSK Investigational Site

Seoul, 152-703, South Korea

Location

GSK Investigational Site

Sungnam -Gyeonggi-do, 463707, South Korea

Location

Related Links

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

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2011
• First Posted: December 5, 2011
• Study Start: January 31, 2012
• Primary Completion: April 30, 2014
• Study Completion: April 30, 2014
• Last Updated: June 20, 2018
• Results First Posted: February 2, 2015

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

KR (5); RU (12); US (11); ES (3); SL (3)