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

• Register: ClinicalTrials.gov
• Last refreshed on: 22 February 2021
• Main ID: NCT03521635
• Date of registration: 11/04/2018
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim
• Public title: 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
• Scientific 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)
• Date of first enrolment: July 3, 2018
• Target sample size: 98
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03521635
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

China

Key inclusion & exclusion 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



Age minimum: 30 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson Disease

Intervention(s)

Drug: Pramipexole IR

Drug: Pramipexole SR

Primary Outcome(s)

Change From Baseline to Week 18 in Parkinson's Disease Sleep Scale 2nd Version (PDSS-2) Total Score [Time Frame: Baseline and Week 18]

Secondary Outcome(s)

Early Morning Off (EMO) Score (Change From Baseline) [Time Frame: Baseline and Week 18]

Responder Rate for Clinical Global Impression of Improvement (CGI-I) [Time Frame: At Week 18]

Scale for Outcomes in Parkinson's Disease (SCOPA)-Sleep Score (Change From Baseline) [Time Frame: Baseline and Week 18]

The Parkinson's Disease Questionnaire (PDQ)-8 Score (Change From Baseline) [Time Frame: Baseline and Week 18]

Responder Rate for Early Morning Off (EMO) Score [Time Frame: At Week 18]

Responder Rate for Patient Global Impression of Improvement (PGI-I) [Time Frame: At Week 18]

Epworth Sleepiness Scale (ESS) Score (Change From Baseline) [Time Frame: Baseline and Week 18]

Nocturnal Hypokinesia Questionnaire (NHQ) Score (Change From Baseline) [Time Frame: Baseline and Week 18]

Responder Rate for Parkinson's Disease Sleep Scale 2nd Version (PDSS-2) Total Score<18 [Time Frame: At Week 18]

Secondary ID(s)

0248-0686

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 16/02/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03521635