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

NCT01154166 | Completed Phase 3 Results

• 1 other identifier: 111528
• Study Type: interventional
• Target: 347
• Locations: 1 country
• Sites: 18

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.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in Total Awake Time Spent "Off" at Week 24 Using Last Observation Carried Forward (LOCF)

  The "off" state is defined as the state in which Parkinson's Disease (PD) symptoms (lack of mobility, tremor, or rigidity) are not adequately controlled by the drug. Participants were asked to record the duration of their "off " periods in 24-hour diary cards prior to each visit on two days of each relevant week. The total number of awake hours spent "off" per 24-hour period was the sum of the hours recorded on the two 24-hour diary cards. Change from Baseline is calculated as the value at Week 24 minus the Baseline value.

  Baseline and Week 24 (Visit 13)

Secondary Outcomes (12)

• Mean Change From Baseline (BL) in the Unified Parkinson Disease Rating Scale (UPDRS) Total Motor Score at Week 24 Using LOCF

  Baseline and Week 24 (Visit 13)

• Mean Change From Baseline in the Percentage of Awake Time Spent "Off" (ATSO) at Week 24 Using LOCF

  Baseline and Week 24

• Mean Change From Baseline in Total Awake Time Spent "on" at Week 24 Using LOCF

  Baseline and Week 24

• Mean Change From Baseline in Total Awake Time "on" Without Troublesome Dyskinesias (TD) at Week 24 Using LOCF

  Baseline and Week 24

• Mean Change From Baseline in the UPDRS Activities of Daily Living (ADL) Score at Week 24 Using LOCF

  Baseline and Week 24

Study Arms (2)

ReQuip PR

EXPERIMENTAL

Ropinirole PR tablets of 2.0 mg, 4.0mg and 8.0 mg

Drug: ReQuip PR

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

ReQuip PR DRUG

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.

ReQuip PR

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (18)

GSK Investigational Site

Guangzhou, Guangdong, 510120, China

Location

GSK Investigational Site

Wuhan, Hubei, 430022, China

Location

GSK Investigational Site

Suzhou, Jiangsu, 215004, China

Location

GSK Investigational Site

Xi'an, Shaanxi, 710061, China

Location

GSK Investigational Site

Chengdu, Sichuan, 610041, China

Location

GSK Investigational Site

Chengdu, Sichuan, 610072, China

Location

GSK Investigational Site

Kunming, Yunnan, 650032, China

Location

GSK Investigational Site

Kunming, Yunnan, 650101, China

Location

GSK Investigational Site

Hangzhou, Zhejiang, 310009, China

Location

GSK Investigational Site

Beijing, 100034, China

Location

GSK Investigational Site

Beijing, 100050, China

Location

GSK Investigational Site

Beijing, 100053, China

Location

GSK Investigational Site

Beijing, 100730, China

Location

GSK Investigational Site

Beijing, 100853, China

Location

GSK Investigational Site

Shanghai, 200025, China

Location

GSK Investigational Site

Shanghai, 200032, China

Location

GSK Investigational Site

Shanghai, 200040, China

Location

GSK Investigational Site

Tianjin, 300052, China

Location

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2010
• First Posted: June 30, 2010
• Study Start: February 15, 2010
• Primary Completion: September 1, 2011
• Study Completion: September 29, 2011
• Last Updated: August 6, 2018
• Results First Posted: August 7, 2012

Record last verified: 2018-06

Locations

CN (18)