Clinical trial NCT00349531: A Phase IV Trial With Pramipexole to Investigate the Effects on RLS Symptoms and Sleep Disturbance in Patients With RLS
Official title: A Phase IV Randomised, Double-blind, Placebo-controlled, Dose Titration Trial With Pramipexole (Sifrol®, Mirapexin®) 0.125-0.75 mg/Day Per os for 12 Weeks to Investigate the Effects on RLS Symptoms (IRLS) and Sleep Disturbance (MOS Sleep Scale) in Out-patients With Idiopathic Restless Legs Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Restless Legs Syndrome
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2006-07-07
Enrollment: 369
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to investigate the effects on RLS symptoms and sleep disturbance of pramipexole (Mirapexin) 0.125 mg/day to 0.75 mg/day per os for 12 weeks, compared to placebo, in the treatment of patients with idiopathic Restless Legs Syndrome


Eligibility criteria: Inclusion Criteria:

1. Written informed consent consistent with ICH-GCP and local IRB/IEC requirements obtained prior to any study procedures being performed and the ability and willingness to comply with study treatment regimen and to attend study assessments.
2. Male or female out-patients aged 18-80 years.
3. Diagnosis of idiopathic RLS according to the clinical RLS criteria of the IRLSSG \[P03-03355\]. All four criteria must be present to fulfil the diagnosis of RLS:

   * An urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs. (Sometimes the urge to move is present without the uncomfortable sensations and sometimes the arms or other body parts are involved in addition to the legs)
   * The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting
   * The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues
   * The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night. (When symptoms are very severe, the worsening at night may not be noticeable but must have been previously present).
4. RLS symptoms present at least 2 to 3 days per week during the last 3 months prior to baseline (Visit 2).
5. IRLS total score \>15 at baseline (Visit 2).

Exclusion Criteria:

1. Women of child-bearing potential who do not use during the trial an adequate method of contraception.
2. Women of child-bearing potential not having negative pregnancy test at screening.
3. Breastfeeding women.
4. Concomitant or previous pharmacologic therapy for RLS with: dopamine agonists or levodopa (within 14 days prior to baseline), levodopa with augmentation, unsuccessful prior treatment with non-ergot dopamine agonists.
5. All treatment less than 14 days or concomitant treatment with medication or dietary supplements which could significantly influence RLS symptoms.
6. Withdrawal symptoms.
7. Pramipexole non-responders in other indications than RLS.
8. Patients with known hypersensitivity to pramipexole or any other component of the investigational product or placebo tablets.
9. Diabetes mellitus requiring insulin therapy.
10. Any of the following laboratory results at screening:

    * any clinically significant abnormalities in laboratory parameters;
    * haemoglobin below LLN.
11. Clinically significant renal disease or calculated creatinine clearance lower than 30 mL/minute.
12. Clinically significant hepatic disease or GPT \>2 times the ULN.
13. Serum ferritin \<10 ng/mL.
14. History of/or malignant melanoma.
15. History of/or clinically significant vision abnormalities.
16. History of/or any other sleep disorder (other than RLS-related).
17. History of/or major depressive disorder or any psychotic disorder, mental disorders or any present Axis I psychiatric disorder according to DSM IV requiring any medical therapy.
18. History of/or clinical signs of suicidal behaviour, suicide ideation or acute suicidal tendency according to the investigator's opinion.
19. History of/or alcohol abuse or drug addiction (within 2 years).
20. Patients on a shift-work-schedule or who are otherwise unable to follow a regular sleep-wake cycle.
21. Participation in an investigational drug study within one month.
22. Any clinically significant conditions that would interfere or constitute a health hazard for the patient.

Primary outcomes:
measure: Primary endpoint: change from baseline after 12 weeks in IRLS total score. Co-primary endpoint: change from baseline after 12 weeks in MOS sleep disturbance score.
timeFrame: 12 weeks after start of treatment
Secondary outcomes:
measure: Secondary endpoints: CGI-I and IRLS responder rate other MOS dimensions, RLS-6 items 4-6, IRLS item 10, VAS ,Verbal Fluency Tests ,RLS-QoL scores PGI responder rate adverse event profile, systolic and diastolic blood pressure, pulse rate
timeFrame: 12 weeks after start of treatment
Other outcomes:
Locations:
city: Kgs. Lyngby
country: Denmark
facility: 248.615.45103 Boehringer Ingelheim Investigational Site
city: København K
country: Denmark
facility: 248.615.45102 Boehringer Ingelheim Investigational Site
city: København NV
country: Denmark
facility: 248.615.45101 Boehringer Ingelheim Investigational Site
city: Vaerløse
country: Denmark
facility: 248.615.45104 Boehringer Ingelheim Investigational Site
city: Espoo
country: Finland
facility: 248.615.35101 Boehringer Ingelheim Investigational Site
city: Joensuu
country: Finland
facility: 248.615.35104 Boehringer Ingelheim Investigational Site
city: Lahti
country: Finland
facility: 248.615.35103 Boehringer Ingelheim Investigational Site
city: Oulu
country: Finland
facility: 248.615.35102 Boehringer Ingelheim Investigational Site
city: Berlin-Steglitz
country: Germany
facility: 248.615.49103 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.615.49109 Boehringer Ingelheim Investigational Site
city: Görlitz
country: Germany
facility: 248.615.49105 Boehringer Ingelheim Investigational Site
city: Hattingen
country: Germany
facility: 248.615.49108 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 248.615.49106 Boehringer Ingelheim Investigational Site
city: Schwerin
country: Germany
facility: 248.615.49102 Boehringer Ingelheim Investigational Site
city: Ulm
country: Germany
facility: 248.615.49101 Boehringer Ingelheim Investigational Site
city: Witten
country: Germany
facility: 248.615.49107 Boehringer Ingelheim Investigational Site
city: Würzburg
country: Germany
facility: 248.615.49104 Boehringer Ingelheim Investigational Site
city: BIrr
country: Ireland
facility: 248.615.35302
city: Carrigtwohill
country: Ireland
facility: 248.615.35301 Boehringer Ingelheim Investigational Site
city: Castlecomer
country: Ireland
facility: 248.615.35303
city: Bari
country: Italy
facility: 248.615.39007 Policlinico di Bari - Università di Bari
city: Dolo (VE)
country: Italy
facility: 248.615.39006 Ospedale Civile di Dolo
city: Genova
country: Italy
facility: 248.615.39002 Ospedale S. Martino - A. O. Università di Genova
city: Messina
country: Italy
facility: 248.615.39008 Policlinico Gaetano Martino
city: Milano
country: Italy
facility: 248.615.39001 Istituto San Raffaele Turro
city: Pavia
country: Italy
facility: 248.615.39004 IRCCS Fondazione Istituto Neurologico "C. Mondino"
city: Pisa
country: Italy
facility: 248.615.39005 Ospedale S. Chiara
city: Udine
country: Italy
facility: 248.615.39003 A. O. Santa Maria della Misericordia
city: Bekkestua
country: Norway
facility: 248.615.47101 Boehringer Ingelheim Investigational Site
city: Fevik
country: Norway
facility: 248.615.47102 Boehringer Ingelheim Investigational Site
city: Moelv
country: Norway
facility: 248.615.47104 Boehringer Ingelheim Investigational Site
city: Oslo
country: Norway
facility: 248.615.47103 Boehringer Ingelheim Investigational Site
city: Tvedestrand
country: Norway
facility: 248.615.47105 Boehringer Ingelheim Investigational Site
city: Avila
country: Spain
facility: 248.615.3408 Hospital Nuestra Señora de Sonsoles
city: Maderid
country: Spain
facility: 248.615.3402
city: Madrid
country: Spain
facility: 248.615.3404 Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: 248.615.3406
city: Madrid
country: Spain
facility: 248.615.3407
city: San Cugat del Valles (Barcelona)
country: Spain
facility: 248.615.3403 Hospital General de Catalunya
city: Göteborg
country: Sweden
facility: 248.615.46101 Boehringer Ingelheim Investigational Site
city: Göteborg
country: Sweden
facility: 248.615.46103 Boehringer Ingelheim Investigational Site
city: Hedemora
country: Sweden
facility: 248.615.46102 Boehringer Ingelheim Investigational Site
city: Örebro
country: Sweden
facility: 248.615.46104 Boehringer Ingelheim Investigational Site
city: Buckshaw Village, Chorley
country: United Kingdom
facility: 248.615.44006 Boehringer Ingelheim Investigational Site
city: Cambridge
country: United Kingdom
facility: 248.615.44004 Boehringer Ingelheim Investigational Site
city: Manchester
country: United Kingdom
facility: 248.615.44007 Boehringer Ingelheim Investigational Site
city: Reading
country: United Kingdom
facility: 248.615.44009 Boehringer Ingelheim Investigational Site
city: Romford
country: United Kingdom
facility: 248.615.44002 Boehringer Ingelheim Investigational Site
city: West Green, Crawley
country: United Kingdom
facility: 248.615.44005 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Hornyak M, Sohr M, Busse M; 604 and 615 Study Groups. Evaluation of painful sensory symptoms in restless legs syndrome: experience from two clinical trials. Sleep Med. 2011 Feb;12(2):186-9. doi: 10.1016/j.sleep.2010.11.007. Epub 2011 Jan 21.