Clinical trial NCT03521635: The SUSTAIN Study Compares the Effects of Sustained and Immediate-release Pramipexole on the noctUrnal Symptoms of paTients With Advanced ParkInsoN's Disease Who Also Take L-Dopa
Official title: A Two- Stage Multicenter, Open-label, Randomized, Active Controlled Parallel Group Study Comparing the Efficacy and Safety of Pramipexole SR Versus Pramipexole IR Administered Orally Over an 18-week Treatment on Nocturnal Symptoms in L-Dopa+ Treated Patients With Advanced Parkinson's Disease (PD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson Disease
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2018-05-11
Enrollment: 98
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: The main objective of the study is to explore firstly, then further evaluate and confirm the efficacy between Pramipexole Sustained Release (SR) versus Pramipexole Immediate Release (IR) on nocturnal symptoms (as measured by the change from baseline to the end of the maintenance period in Parkinson's Disease Sleep Scale 2nd version (PDSS-2) score) in L-dopa+ treated patients with advanced Parkinson's disease (PD).


Eligibility criteria: Inclusion Criteria:

* Male or female patient with advanced idiopathic Parkinson's disease (PD) confirmed by at least bradykinesia and one of the following signs: resting tremor, rigidity.
* Diagnosed as Parkinson's disease, with at least 2 years' PD history.
* Of age ≥ 30 years at time of diagnosis.
* Modified Hoehn and Yahr stage of 2 to 4 at on-time.
* They must have clinically relevant sleep disturbances (i.e. Parkinson's Disease Sleep Scale 2nd version (PDSS-2) total score ≥18 at baseline).
* They must feel uncomfortable at night because they were unable to turn around in bed or move due to immobility (i.e. the scoring of question 9 in PDSS-2 ≥ 2, that means frequency is at least 2 to 3 days during the past week).
* They must have early morning off (i.e. the frequency of "feeling like bodily movements are poor when you wake up?" is at least 2 to 3 days during the past week).
* Patient must have motor fluctuations (at least 2 cumulative hours of off-time every day during waking hours, documented on a patient diary completed for 2 consecutive days before randomization visit).
* Patients must be treated with Levodopa combined with a Dopa-Decarboxylase-inhibitor (L-Dopa+) (i.e. standard and/or controlled release Levodopa/DDC inhibitor), or with a combination of L-Dopa+ and entacapone, at an optimized dose according to investigator's judgment, this dose being stable for at least 4 weeks prior to randomization visit.
* Patients must not have been treated with sustained release dopaminergic drug (i.e. sustained release Levodopa/Dopa-Decarboxylase (DDC) inhibitor) after supper, or any anti-PD medication after 9pm within 4 weeks prior to randomization visit.
* Patients must not have been treated with dopamine agonists within 4 weeks prior to randomization visit. A concomitant treatment with one or more of the following drugs will be allowed (at a stable dose for at least 4 weeks prior to randomization visit and the investigator does not intend to change this treatment during the treatment phase):

  * Anti-parkinsonian anticholinergics;
  * Selegiline, rasagiline, or other Monoamine Oxydase (MAO)-B-Inhibitor;
  * Amantadine;
  * Entacapone (or other Catechol-O-Methyltransferase (COMT)-Inhibitor).
* Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
* Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.

Exclusion criteria:

* Secondary parkinsonian syndromes due to drugs (e.g., metoclopramide, flunarizine), metabolic disorders (e.g., Wilson's disease), encephalitis or degenerative diseases (e.g., progressive supranuclear palsy).
* Dementia, as defined by a Mini-Mental State Exam score \< 24 at screening visit.
* Any psychiatric disorder according to DSM-V Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria that could prevent compliance or completion of the study and/or put the patient at risk if he/she takes part in the study.
* History of psychosis, except history of drug induced hallucinations (provided the investigator considers that participation to the trial would not represent a significant risk for the patient).
* History of deep brain stimulation.
* History of nucleus lesioning.
* Clinically significant electrocardiogram (ECG) abnormalities at screening visit, according to investigator's judgement.
* Clinically significant hypotension (i.e. supine systolic blood pressure \< 90 mmHg) and/or symptomatic orthostatic hypotension (i.e. clinical symptoms of orthostatic hypotension associated with a decline ≥ 20 mmHg in systolic blood pressure and a decline ≥ 10 mmHg in diastolic blood pressure, at 1 minute after standing compared with the previous supine systolic and diastolic blood pressure obtained after 5 minutes of quiet rest) at screening or randomization visit.
* Major surgery (major according to the investigator's assessment) performed within 12 weeks prior to randomization or planned within 12 months after screening, e.g. hip replacement.
* Any other clinically significant disease, whether treated or not, that could put the patient at risk or could prevent compliance or completion of the study.
* Serious Sleep Apnea Hypopnea Syndrome (i.e. the scoring of question 15 in Parkinson's Disease Sleep Scale 2nd version (PDSS-2)≥ 3, that means frequency is at least 4 to 5 days during the past week )
* Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
* Serum levels of Aspartate Aminotransferase (AST)(SGOT), Alanine Aminotransferase (ALT)(SGPT), alkaline phosphatases or total bilirubin \>2 ULN (on screening lab test).
* Patients with a creatinine clearance \< 50 mL/min (estimated by the local lab / the investigator using the Modification of Diet in Renal Disease (MDRD, please refer to Appendix 10.1), and calculated on screening lab test).
* Any hypnotic medication within 4 weeks prior to the randomization visit (i.e. diazepam, clonazepam, estazolam, alprazolam, zolpidem, etc.).
* Any medication (including intra-muscular formulations) with central dopaminergic antagonist activity within 4 weeks prior to the randomization visit (i.e. typical neuroleptics, atypical antipsychotics, reserpine, methyldopa, centrally-active antiemetics, etc.).
* Any of the following drugs within 4 weeks prior to randomization visit: methylphenidate, cinnarizine, amphetamines.
* Flunarizine within 3 months prior to randomization visit.
* Known hypersensitivity to Pramipexole or its excipients.
* Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
* Previous enrolment in this trial.
* Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatment(s).
* Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial.
* Women who are pregnant, nursing, or who plan to become pregnant in the trial.

Primary outcomes:
measure: Change From Baseline to Week 18 in Parkinson's Disease Sleep Scale 2nd Version (PDSS-2) Total Score
timeFrame: Baseline and Week 18
Secondary outcomes:
measure: Nocturnal Hypokinesia Questionnaire (NHQ) Score (Change From Baseline)
timeFrame: Baseline and Week 18
measure: Scale for Outcomes in Parkinson's Disease (SCOPA)-Sleep Score (Change From Baseline)
timeFrame: Baseline and Week 18
measure: Early Morning Off (EMO) Score (Change From Baseline)
timeFrame: Baseline and Week 18
measure: Responder Rate for Parkinson's Disease Sleep Scale 2nd Version (PDSS-2) Total Score<18
timeFrame: At Week 18
measure: Responder Rate for Early Morning Off (EMO) Score
timeFrame: At Week 18
measure: The Parkinson's Disease Questionnaire (PDQ)-8 Score (Change From Baseline)
timeFrame: Baseline and Week 18
measure: Responder Rate for Clinical Global Impression of Improvement (CGI-I)
timeFrame: At Week 18
measure: Responder Rate for Patient Global Impression of Improvement (PGI-I)
timeFrame: At Week 18
measure: Epworth Sleepiness Scale (ESS) Score (Change From Baseline)
timeFrame: Baseline and Week 18
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Beijing Hospital
city: Chengdu
country: China
facility: West China Hospital
city: Guangzhou
country: China
facility: The First Afiliated Hospital, Sun Yet-sen University
city: Hangzhou
country: China
facility: 2nd Affiliated Hosp Zhejiang University College of Medical
city: Nanjing
country: China
facility: Brain Hospital Affiliated to Nanjing Med University
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
city: Shenyang
country: China
facility: The First Hospital of Chinese Medical University
city: Suzhou City
country: China
facility: The Second Affiliated Hospital of Soochow University
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Wuhan
country: China
facility: Wuhan Union Hospital
city: Xian
country: China
facility: First Affiliated Hospital of Xi'an JiaoTong University
Study officials:
References: