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

NCT01494532 | Completed Phase 4 Results

• 1 other identifier: 111569
• Study Type: interventional
• Target: 352
• Locations: 7 countries
• Sites: 52

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline (BL) in Total Awake Time Spent "Off" at Week 4 of Maintenance Period

  "Off" time is defined as the state in which the participants(par) symptoms include lack of mobility(bradykinesia) with or without additional features such as tremor or rigidity. Par were asked to record awake time "off ", awake time "on", troublesome dyskinesias(TD) during awake time "on", or time asleep for 30 minute intervals in 24 hr diary cards for 2 days preceding visits. Total number of awake hrs spent "off" per 24-hr period was the average of the 2 diary cards of the sum of awake hours spent "off" in each 24-hr diary card. BL is the last non-missing assessment measured on or before the first dose, change from BL was calculated by subtracting the BL values from the MP Week 4 values. Mixed Model Repeated Measures (MMRM) model used BL total awake time 'Off', treatment, visit and treatment by visit

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

Secondary Outcomes (23)

• Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) "Off" Time at Week-4 of Maintenance Period

  Week 4 of the Maintenance Period (Study Week 17)

• Percentage of Participants With a >=1 Hour Reduction in Baseline "Off" Time at Week 4 of the Maintenance Period

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

• Percentage of Participants With a >=2 Hours Reduction in Baseline "Off" Time at Week 4 of the Maintenance Period

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

• Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period

  Week 4 of the Maintenance Period (Study Week 17)

• Change From Baseline in Absolute Awake Time Spent "on" Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period

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

Study Arms (2)

ropinirole

EXPERIMENTAL

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

Drug: ropinirole/L-dopa

placebo

PLACEBO COMPARATOR

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

Drug: placebo/L-dopa

Interventions

ropinirole/L-dopa DRUG

Ropinirole as adjunctive therapy with L-dopa

ropinirole

placebo/L-dopa DRUG

Placebo as adjunctive therapy with L-dopa

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (52)

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

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

Springfield, Massachusetts, 01104, United States

Location

GSK Investigational Site

Forest Hills, New York, 11375, United States

Location

GSK Investigational Site

Richmond, Virginia, 23249, United States

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1200AAT, Argentina

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1419AHN, Argentina

Location

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, C1192AAW, Argentina

Location

GSK Investigational Site

San Martín, Buenos Aires, 1650, Argentina

Location

GSK Investigational Site

Buenos Aires, B1602DBG, Argentina

Location

GSK Investigational Site

Buenos Aires, C1133AAW, Argentina

Location

GSK Investigational Site

Buenos Aires, C1426AHA, Argentina

Location

GSK Investigational Site

Caba, 1209, Argentina

Location

GSK Investigational Site

Valdivia, Los Lagos Region, 5090145, Chile

Location

GSK Investigational Site

Viña del Mar, Región de Valparaíso, 2570017, Chile

Location

GSK Investigational Site

Santiago, 7500551, Chile

Location

GSK Investigational Site

Santiago, 7500710, Chile

Location

GSK Investigational Site

Santiago, 8260094, Chile

Location

GSK Investigational Site

Tallinn, 10138, Estonia

Location

GSK Investigational Site

Tallinn, 10617, 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

Yaroslavl, 150030, 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, 826 06, Slovakia

Location

GSK Investigational Site

Bratislava, 831 03, Slovakia

Location

GSK Investigational Site

Bratislava, 833 05, Slovakia

Location

GSK Investigational Site

Dubnica nad Váhom, 1841, Slovakia

Location

GSK Investigational Site

Trnava, 91702, Slovakia

Location

GSK Investigational Site

Anyang-si, 431-070, South Korea

Location

GSK Investigational Site

Busan, 602-715, South Korea

Location

GSK Investigational Site

Daejeon, 371718, South Korea

Location

GSK Investigational Site

Seongnam-si Gyeonggi-do, 463-707, South Korea

Location

GSK Investigational Site

Seoul, 130-702, 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, 463712, 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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2011
• First Posted: December 19, 2011
• Study Start: April 2, 2012
• Primary Completion: November 18, 2014
• Study Completion: November 18, 2014
• Last Updated: June 20, 2018
• Results First Posted: December 3, 2015

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

AR (8); ES (2); SL (7); RU (13); US (9); CL (5); KR (8)