Last updated: 11/07/2018 03:33:50
A fixed dose study of ropinirole prolonged release as adjunctive treatment in patients with advanced Parkinson’s diseaseTANDEM-569
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: This is a double blind, fixed dose, parallel group study to characterize the dose responseof ropinirole PR as adjunctive therapy to L-dopa in patients with late stage Parkinson’sdisease. The primary endpoint of this study, mean change from baseline in total awaketime spent “off’ is the same endpoint as used in the ropinirole PR pivotal study foradvanced Parkinson’s disease patients. This study includes a wide range of ropiniroledoses (4-24mg) with the 8mg, 12mg, and 16mg per day doses powered to detect a 1.7hour difference in total awake time spent “off” compared with placebo. The dose of Ldopawill remain stable through the study, unless the subject experiences tolerabilityissues that require an L-dopa dose reduction. Up to three L-dopa dose reductions areallowed, making a total reduction of up to approximately 30%. Keeping the L-dopa doseconstant where possible is important to avoid confounding the efficacy data. Clinicalreview of the primary and secondary endpoints will be performed in order to establish thelowest maximally effective therapeutic dose.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
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:
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Interventions:
Drug: ropinirole/L-dopa
Drug: placebo/L-dopa
Enrollment:
352
Observational study model:
Not applicable
Primary completion date:
2014-18-11
Time perspective:
Not applicable
Clinical publications:
Zesiewicz T, Chriscoe S, Jimenez T, Upward J, Davy M, VanMeter S,. A randomized, fixed-dose, Dose–response Study of Ropinirole Prolonged Release in Advanced Parkinson’s Disease . Neurodegener Dis Manag. 2017;7(1):61-72.
Medical condition
Parkinson Disease
Product
ropinirole
Collaborators
Not applicable
Study date(s)
April 2012 to November 2014
Type
Interventional
Phase
4
Participation criteria
Sex
Female & Male
Age
30+ years
Accepts healthy volunteers
No
- 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.
- Late stage advanced subjects demonstrating incapacitating peak dose or diphasic
- dyskinesia on their stable dose of L-dopa
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Seongnam-si Gyeonggi-do, South Korea, 463-707
Status
Study Complete
Location
GSK Investigational Site
Viña del Mar, Valparaíso, Chile, 2570017
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1192AAW
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Forest Hills, New York, United States, 11375
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Boca Raton, Florida, United States, 33486
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1133AAW
Status
Study Complete
Location
GSK Investigational Site
Richmond, Virginia, United States, 23249
Status
Study Complete
Location
GSK Investigational Site
Pasedena, California, United States, 91105
Status
Study Complete
Location
GSK Investigational Site
San Martin, Buenos Aires, Argentina, 1650
Status
Study Complete
Location
GSK Investigational Site
Valdivia, Región De Los Lagos, Chile, 5090145
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1419AHN
Status
Study Complete
Location
GSK Investigational Site
Ventura, California, United States, 93003
Status
Study Complete
Location
GSK Investigational Site
Springfield, Massachusetts, United States, 01104
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Fountain Valley, California, United States, 92708
Status
Study Complete
Location
GSK Investigational Site
Reseda, California, United States, 91355
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2014-18-11
Actual study completion date
2014-18-11
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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