Clinical trial NCT01494532: A Fixed Dose Study of Ropinirole Prolonged Release as Adjunctive Treatment in Patients With Advanced Parkinson's Disease
Official title: A Fixed Dose, Dose-response Study of Ropinirole Prolonged Release (PR) as Adjunctive Treatment to L-dopa in Patients With Advanced Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson Disease
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-12-19
Enrollment: 352
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change From Baseline (BL) in Total Awake Time Spent "Off" at Week 4 of Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Secondary outcomes:
measure: Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) "Off" Time at Week-4 of Maintenance Period
timeFrame: Week 4 of the Maintenance Period (Study Week 17)
measure: Percentage of Participants With a >=1 Hour Reduction in Baseline "Off" Time at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Percentage of Participants With a >=2 Hours Reduction in Baseline "Off" Time at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period
timeFrame: Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in Absolute Awake Time Spent "on" Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in Absolute Awake Time Spent "on" at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Percent Change From Baseline in Awake Time Spent "Off" at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Percent Change From Baseline in Awake Time Spent "on" Without TD at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Percent Change From Baseline in Awake Time Spent "on" at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in the Percent Awake Time Spent "Off" at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in the Percent Awake Time Spent "on" Without TD at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in the Percent Awake Time Spent "on" at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in the Percent of a 24-hour Day Spent "Off" at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in the Percent of a 24- Hour Day Spent "on" Without TD at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in the Percent of a 24-hour Day Spent "on" at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an "on" State, at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an "on" State, at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in UPDRS ADL Score With Participants in an "Off" State, at Week 4 of the Maintenance Period
timeFrame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
measure: Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period
timeFrame: Baseline (BL) and Week 4 of the Maintenance Period (Study Week 17)
measure: Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy
timeFrame: From start of study treatment until end of treatment (assessed up to 18 weeks)
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: GSK Investigational Site
state: California
city: Pasadena
country: United States
facility: GSK Investigational Site
state: California
city: Reseda
country: United States
facility: GSK Investigational Site
state: California
city: Ventura
country: United States
facility: GSK Investigational Site
state: California
city: Boca Raton
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Springfield
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Forest Hills
country: United States
facility: GSK Investigational Site
state: New York
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: San Martin
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Caba
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Valdivia
country: Chile
facility: GSK Investigational Site
state: Región De Los Lagos
city: Viña del Mar
country: Chile
facility: GSK Investigational Site
state: Valparaíso
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Anyang-Si
country: Korea, Republic of
facility: GSK Investigational Site
city: Busan
country: Korea, Republic of
facility: GSK Investigational Site
city: Daejeon
country: Korea, Republic of
facility: GSK Investigational Site
city: Seongnam-si Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Sungnam
country: Korea, Republic of
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: GSK Investigational Site
city: Kazan
country: Russian Federation
facility: GSK Investigational Site
city: Krasnoyarsk
country: Russian Federation
facility: GSK Investigational Site
city: Kursk
country: Russian Federation
facility: GSK Investigational Site
city: Novosibirsk
country: Russian Federation
facility: GSK Investigational Site
city: Omsk
country: Russian Federation
facility: GSK Investigational Site
city: Perm
country: Russian Federation
facility: GSK Investigational Site
city: Saratov
country: Russian Federation
facility: GSK Investigational Site
city: Smolensk
country: Russian Federation
facility: GSK Investigational Site
city: St.Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Ufa
country: Russian Federation
facility: GSK Investigational Site
city: Yaroslavl
country: Russian Federation
facility: GSK Investigational Site
city: Banska Bystrica
country: Slovakia
facility: GSK Investigational Site
city: Bratislava
country: Slovakia
facility: GSK Investigational Site
city: Bratislava
country: Slovakia
facility: GSK Investigational Site
city: Bratislava
country: Slovakia
facility: GSK Investigational Site
city: Bratislava
country: Slovakia
facility: GSK Investigational Site
city: Dubnica Nad Vahom 1
country: Slovakia
facility: GSK Investigational Site
city: Trnava
country: Slovakia
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: