Clinical trial NCT01154166: A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel Group Study of Six Months Treatment With Ropinirole PR as Adjunctive Therapy in Patients With Parkinson's Disease Who Are Not Optimally Controlled on L-Dopa
Official title: A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel Group Study of Six Months Treatment With Ropinirole PR as Adjunctive Therapy in Patients With Parkinson's Disease Who Are Not Optimally Controlled on L-Dopa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson Disease
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-06-30
Enrollment: 347
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 phase III, multicenter, randomized, double-blind, parallel group, placebo-controlled study to compare the efficacy of 6-months therapy of ropinirole Prolonged Release (PR) with that of placebo as adjunctive therapy to L-dopa in Parkinson's disease patients not optimally controlled on L-dopa. This study will be conducted in China. Subjects will have total 14 visits over the 26 week duration of the study.

Following screening, eligible subjects will receive study medication during the fourteen day placebo run-in period which they will be instructed to take in addition to their background L-dopa. If subjects are still eligible at the end of the placebo run-in period they will be randomized (1:1) to receive once daily doses of ropinirole PR or identical appearing placebo tablets. Dosing will start at 2 mg ropinirole PR, or placebo equivalent. During the 24 week treatment phase, the subjects dose will be adjusted according to the recommended schedule to achieve symptomatic control. All subjects must be titrated to a minimum dose of 6 mg/day. If sufficient symptomatic control is not achieved or maintained at a dose of 6mg/day of ropinirole PR, the daily dose should be increased by 2mg at weekly or longer intervals up to a dose of 8mg/day.If sufficient symptomatic control is still not achieved or maintained at a dose of 8mg/day of ropinirole PR, the daily dose should be increased by 4mg at two weekly or longer intervals. Further dose titration should not be conducted within the final 8 weeks of the treatment phase. The maximum recommended daily dose is 24mg.

The planned reduction in L-dopa dose will begin once subjects are titrated to Dose Level 4 or Dose Level 5 of study medication. For each increase in study medication, there will be a corresponding decrease in L-dopa. If loss of symptom control occurs with the reduction in the background L-dopa dose, the dose of study medication should be increased to the next higher dose level with no adjustment in the dose of L-dopa. If loss of symptom control persists, subjects should be titrated up an additional dose level. Subjects who do not experience an improvement in symptoms following upward titration by 2 dose levels of study medication, should be "rescued" with L-dopa.

Subjects will be dispensed down-titration medication at the study completion/early withdrawal visit if the patient did not enter extension study and should be scheduled to return for a follow up visit 4 to 14 days after the last dose of study medication. The extension study aim to evaluate the safety profile of ReQuip PR during long-term treatment in subjects with advanced parkinson's disease.


Eligibility criteria: Inclusion Criteria:

* 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 (such as oral contraception, surgical sterilization, intrauterine device \[IUD\], or diaphragm IN ADDITION to spermicidal foam and condom on male partner, or systemic contraception \[i.e. Norplant System\]), during the study and for at least one month prior to randomisation and one month following completion of the study.
* 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 four weeks prior to screening.
* Provide written informed consent for this study
* A minimum of 3 hours awake time"off " for each diary day recorded during the Placebo Run-In Period.
* 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 biphasic dyskinesia on their stable dose of L-dopa.
* Presence, or history within the previous 3 months, of significant and/or uncontrolled psychiatric, hematological, renal, hepatic, endocrinological, neurological (other than Parkinson.s Disease), or cardiovascular disease or active malignancy (other than basal cell cancer);
* Any abnormality, at Screening, that the investigator deems to be clinically relevant on history, physical examination and in diagnostic laboratory tests including ECG;
* Unstable liver disease, cirrhosis, known biliary abnormalities(except Gilbert's syndrome or asymptomatic gallstones) or AST or ALT\>2xULN or alk phos and bilirubin\>1.5 xULN
* Recent history of severe dizziness or fainting due to postural hypotension on standing.
* Clinical dementia that in the judgment of the investigator would preclude assessment of the subject.
* Recent history or current evidence of drug abuse or alcoholism.
* Consumption of any dopamine agonist within four weeks of the screening visit.
* 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 PR.
* 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. Subjects already on chronic therapy with any of these agents may be enrolled but must remain on stable doses of the agent from 7 days prior to enrolment through the end of the Treatment Period.
* Use of an investigational drug within 30 days or 5 half-lives (which ever is longer).

Primary outcomes:
measure: Mean Change From Baseline in Total Awake Time Spent "Off" at Week 24 Using Last Observation Carried Forward (LOCF)
timeFrame: Baseline and Week 24 (Visit 13)
Secondary outcomes:
measure: Mean Change From Baseline (BL) in the Unified Parkinson Disease Rating Scale (UPDRS) Total Motor Score at Week 24 Using LOCF
timeFrame: Baseline and Week 24 (Visit 13)
measure: Mean Change From Baseline in the Percentage of Awake Time Spent "Off" (ATSO) at Week 24 Using LOCF
timeFrame: Baseline and Week 24
measure: Mean Change From Baseline in Total Awake Time Spent "on" at Week 24 Using LOCF
timeFrame: Baseline and Week 24
measure: Mean Change From Baseline in Total Awake Time "on" Without Troublesome Dyskinesias (TD) at Week 24 Using LOCF
timeFrame: Baseline and Week 24
measure: Mean Change From Baseline in the UPDRS Activities of Daily Living (ADL) Score at Week 24 Using LOCF
timeFrame: Baseline and Week 24
measure: Number of Responders Based on the Clinical Global Impression (CGI) Global Improvement Scale Using LOCF
timeFrame: Week 24
measure: Number of Participants Requiring Reinstatement of L-dopa Following a Dose Reduction Using LOCF
timeFrame: Week 24
measure: Number of Responders to Study Treatment Using LOCF
timeFrame: Baseline to Week 24
measure: Mean Change From Baseline in the Depression Scores on the Hamilton Depression Rating Scale (HAMD-17) Using LOCF
timeFrame: Baseline and Week 24
measure: Mean Change From Baseline (BL) in the Parkinson's Disease Sleep Scale (PDSS) Total Score Using LOCF
timeFrame: Baseline and Week 24
measure: Mean Change From Baseline in the Parkinson's Disease Quality of Life Scores (PDQ39) Using LOCF
timeFrame: Baseline and Week 24
measure: Time to Reinstatement of L-dopa Following a Reduction in Dose Using LOCF
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Wuhan
country: China
facility: GSK Investigational Site
state: Hubei
city: Suzhou
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Xian
country: China
facility: GSK Investigational Site
state: Shaanxi
city: Chengdu
country: China
facility: GSK Investigational Site
state: Sichuan
city: Chengdu
country: China
facility: GSK Investigational Site
state: Sichuan
city: Kunming
country: China
facility: GSK Investigational Site
state: Yunnan
city: Kunming
country: China
facility: GSK Investigational Site
state: Yunnan
city: Hangzhou
country: China
facility: GSK Investigational Site
state: Zhejiang
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Tianjin
country: China
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: