A Study to Evaluate the Efficacy of 18 to 24mg/Day Ropinirole Controlled Release (CR) Tablets in Early and Advanced Parkinson's Disease (PD) Patients.

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01929317
• Date of registration: 22/08/2013
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A Study to Evaluate the Efficacy of 18 to 24mg/Day Ropinirole Controlled Release (CR) Tablets in Early and Advanced Parkinson's Disease (PD) Patients.
• Scientific title: A Study ROP116991, Clinical Evaluation of 18 to 24mg/Day Ropinirole CR for Parkinson's Disease.
• Date of first enrolment: August 28, 2013
• Target sample size: 81
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01929317
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Japan

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

Inclusion criteria at the start of the screening

- Patients who are diagnosed as Parkinson's Disease with severity of the modified Hoehn
& Yahr criteria Stages I-IV.

- 1) Monotherapy subject: Subjects who have never received L-dopa, or subjects who have
had prior exposure to L-dopa (up to 450 milligram (mg)/day) for up to 3 months in
total and L-dopa treatment has been discontinued, for a minimum of 4 weeks prior to
the screening phase. 2) L-dopa adjunct subject: Subjects receiving L-dopa (up to 450
mg/day) for at least 4 weeks prior to the screening phase.

- Patients receiving 15mg/day Ropinirole IR or 16mg/day Ropinirole CR for 4 weeks prior
to the screening phase, UPDRS Part III total (on) scores is 10 points or more at
screening visit and can expect clinical efficacy by increasing Ropinirole CR.

- Age: 20years or older (at the time of informed written consent)

- Informed consent: Patients who are able to give informed written consent in person.
(i.e. patients who are capable of giving informed written consent on their own)

- Sex: Either sex. Women of child-bearing potential will be eligible for inclusion in
this study. However they have to have a negative pregnancy test at the screening visit
and will have to agree to further pregnancy testing at the time points determined in
study assessments and procedures and practice one of the methods of contraception
mentioned in the protocol from the screening visit until the end of the follow-up
examination - Outpatient status

- corrected QT (QTc) <450 millisecond (msec) or <480msec for subjects with Bundle Branch
Block. The QTc should be based on single or averaged QTc values of triplicate
electrocardiograms (ECGs) obtained over a brief recording period.

- Liver function tests: Patients with aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) < 2x upper limit of normal (ULN); and Alkaline Phosphatase and
bilirubin =< 1.5xULN (isolated bilirubin > 1.5ULN is acceptable if bilirubin is
fractionated and direct bilirubin < 35%) at the screening visit.

Randomization Criteria

- Patients whose UPDRS Part III total (on) scores is 10 points or more at week 0

- Patients who did not achieve an optimal therapeutic response by treatment with
16mg/day Ropinirole CR and required higher dose of Ropinirole CR

- Patients who are 80% or more compliant taking study drug

Exclusion Criteria

- Late stage advanced patients demonstrating incapacitating peak dose or biphasic
dyskinsia on their stable dose of L-dopa.

- Patients who have used any other dopamine agonist (except for Ropinirole IR and CR)
within 4 weeks prior to the screening phase.

- Patients who have been treated with the following drugs at 4 weeks or earlier before
the start of the screening phase, and whose treatment regimen of the drug has been
changed. Anticholinergic agents: trihexyphenidyl hydrochloride, piroheptine
hydrochloride, mazaticol hydrochloride, metixene hydrochloride, biperiden
hydrochloride, profenamine, amantadine hydrochloride,droxidopa, citicoline, selegiline
hydrochloride, entacapone, zonisamide, Estrogens, CYP1A2 inhibitors.

- Patients who have been changing in smoking habit (started or stopped smoking) within
the screening phase.

- Patients who have been treated with any other investigational drug within 12 weeks
prior to the screening phase.

- Patients who present serious physical signs and symptoms other than those of the PD
(e.g. cardiac/hepatic/renal disorder and haematopoietic disorder).

- Patients with symptomatic postural hypotension. (e.g. dizziness and syncope).

- Patients with a current or history of drug abuse or alcoholism.

- Patients with severe dementia such as score 3 or 4 of the UPDRS item 1 (Mentation,
behaviour, and mood).

- Patients with current or history of major psychosis (e.g. schizophrenia or psychotic
depression) such as score 3 or 4 of the UPDRS item 2 (thought disorder) or item
3(depression).

- Patients who have received surgical treatment for PD in the past (e.g. pallidectomy,
deep brain stimulation).

- Female patients who are pregnant or lactating, who may be pregnant, or who plan for
pregnancy during the study or within 30 days after the last dose of the study drug.

- Unstable liver disease (as defined by the presence of ascites, encephalopathy,
coagulapathy, hypoalbuminaemia, oesophageal or gastric varices or persistent
jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's
syndrome or asymptomatic gallstones). Chronic hepatitis B administered
immunosuppressive agents due to risk of hapatitis B reactivation.

- Patients with a history of drug allergy to Ropinirole hydrochloride.

- Except for patients with a history of basal cell carcinoma, patients with a current or
history of cancer or malignant tumor within 5 years prior to the screening phase.

- Others whom the investigator (subinvestigator) considers ineligible for the study.



Age minimum: 20 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson Disease

Intervention(s)

Drug: Ropinirole CR 2mg tablet

Drug: Ropinirole CR 8mg tablet

Drug: Ropinirole CR matching Placebo tablet

Primary Outcome(s)

Mean Change From Baseline (Week 0) in UPDRS Part III Total Score at Week 12 in the CR High-dose Group [Time Frame: Baseline and Week 12]

Secondary Outcome(s)

Change From Baseline in the Japanese UPDRS Part 2 Total Score at the Indicated Visits by the on/Off Status in the Long Term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Change From Baseline in the Percentage of Awake Time Spent "Off" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct in Long Term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Percent Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Long Term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Change From Baseline in Actual Hours of Awake Time Spent "On" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Change From Baseline in Actual Hours of Awake Time Spent "On" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct in Long Term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Change From Baseline in Actual Hours of Awake Time Spent "On" Without Troublesome Dyskinesias at the Indicated Visits Only in Participants Who Received L-dopa Adjunct in Long Term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Change From Baseline in the Actual Hours of Awake Time Spent "Off" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct in Long Term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Change From Baseline in the Percentage of Awake Time Spent "Off" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Number of Participants Achieving a 30% and 20% Reduction From Baseline in the UPDRS Total Part 3 Score at the Indicated Visits in Long Term Phase. [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49, 52]

Percent Change From Baseline in the Japanese UPDRS Part 2 Total Score at the Indicated Visits by the on/Off Status in the Long-term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Long-term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Long Term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Number of Participants With an Improvement (Responder) in the Clinical Global Impression (CGI) Global Improvement Scale at Week 12 [Time Frame: Week 12]

Percent Change From Baseline in the Japanese UPDRS Part 3 Total Score at the Indicated Visits in the Long Term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Percent Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Change From Baseline in Actual Hours of Awake Time Spent "On"Without Troublesome Dyskinesias at the Indicated Visits Only in Participants Who Received L-dopa Adjunct [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Change From Baseline in Percentage of Awake Time Spent "On" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct in Long Term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Change From Baseline in Percentage of Awake Time Spent "On" Without Troublesome Dyskinesias at the Indicated Visits Only in Participants Who Received L-dopa Adjunct in Long Term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Change From Baseline in the Actual Hours of Awake Time Spent "Off" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Number of Participants Remaining in the Study [Time Frame: From the start of the study medication (Week 0) until Week 52]

Percent Change From Baseline in the Japanese UPDRS Part 3 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Change From Baseline in the Japanese UPDRS Part 2 Total Score at the Indicated Visits by the on/Off Status in the Dose Increase Effect Verification Phase [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Mean Change From Baseline in UPDRS Part 3 Total Score at the Indicated Visits for Long Term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49, 52]

Percent Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Percent Change From Baseline in the Japanese UPDRS Part 2 Total Score at the Indicated Visits by the on/Off Status in the Dose Increase Effect Verification Phase [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Mean Change From Baseline (Week 0) in UPDRS Part III Total Score at the Indicated Visits [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Number of Participants Achieving a 30% and 20% Reduction From Baseline in the UPDRS Total Part 3 Score at the Indicated Visits in the Dose Increase Effect Verification Phase [Time Frame: Baseline, Weeks, 2, 4, 6, 8 and 12]

Percent Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Long-term Phase [Time Frame: Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52]

Secondary ID(s)

116991

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 21/05/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01929317