Clinical trial NCT00356096: Phase IV Trial With Pramipexole to Evaluate Safety and Efficacy in Patients With RLS Associated With Mood Disturbances
Official title: A Phase IV Randomised, Double-blind, Placebo-controlled, Dose Titration Trial With 0.125-0.75 mg/Day Pramipexole (Sifrol®, Mirapexin®) Orally for 12 Weeks to Investigate the Safety and Efficacy in Out-patients With Idiopathic Restless Legs Syndrome Associated With Mood Disturbances
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Restless Legs Syndrome
Depression
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2006-07-25
Enrollment: 404
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 determine the efficacy of pramipexole 0.125 mg to 0.75 mg daily versus placebo on RLS symptoms and on associated mood disturbances and depressive symptoms, after 12 weeks of treatment


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. In addition all of the following must be demonstrated at Visit 2 (baseline):

IRLS total score \>15 A score of \>=2 for item 10 of the IRLS rating scale

Exclusion Criteria:

1. Women of child-bearing potential who do not use an adequate method of contraception
2. Any women of child-bearing potential not having negative pregnancy test at screening
3. Breastfeeding women
4. Concomitant or previous pharmacologic therapy for RLS
5. All treatment less than 14 days before baseline or concomitant treatment with medication or dietary supplements, which could significantly influence RLS symptoms
6. Withdrawal symptoms of any medication must not be present at baseline
7. Previous pramipexole non-responders in other indications than RLS.
8. Hypersensitivity to pramipexole or any other component of the investigational product
9. Diagnosis of diabetes mellitus requiring insulin
10. Any of the following laboratory results at screening: clinically significant abnormalities at the investigatos discretion; Hb below lower limit of normal
11. Clinically significant renal disease at screening
12. Clinically significant hepatic disease at screening
13. Serum ferritin \<10 ng/mL at screening.
14. History of/or malignant melanoma.
15. History of/or clinically significant vision abnormalities
16. History of/or any other sleep disorder
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, or BDI-II total score \>28
18. History of/or clinical signs of suicidal behaviour, suicide ideation or acute suicidal tendency according to the investigators opinion
19. History of/or alcohol abuse or drug addiction within the last 2 years before screening
20. Patients on a shift-work-schedule or otherwise unable to follow a regular sleep-wake cycle
21. Participation in an investigational drug study within one month prior to the start of this study
22. Patients with any clinically significant conditions that in the opinion of the investigator

Primary outcomes:
measure: The primary endpoint is the change from baseline after 12 weeks of treatment in: IRLS total score, IRLS item 10 score and BDI-II total score
timeFrame: 12 weeks
Secondary outcomes:
measure: The following endpoints will be analysed: CGI-I, IRLS and BDI-II responder rate, VAS score for pain in limbs, RLS-6 item scores, HADS-A score, RLS-QoL score, PGI responder rate, Adverse events profile, Systolic and diastolic blood pressure, Pulse rate
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Espoo
country: Finland
facility: 248.604.35801 Boehringer Ingelheim Investigational Site
city: Helsinki
country: Finland
facility: 248.604.35805 Boehringer Ingelheim Investigational Site
city: Lahti
country: Finland
facility: 248.604.35803 Boehringer Ingelheim Investigational Site
city: Oulu
country: Finland
facility: 248.604.35802 Boehringer Ingelheim Investigational Site
city: Bron
country: France
facility: 248.604.3301A HOP Le Vinatier,Psychiat,Bron
city: Lille cedex
country: France
facility: 248.604.3304B Hôpital Roger Salengro
city: Montbrison
country: France
facility: 248.604.3307A Cabinet Médical
city: Montpellier cédex 5
country: France
facility: 248.604.3303A Hôpital Gui de Chauliac
city: Montpellier cédex 5
country: France
facility: 248.604.3303C Hôpital Gui de Chauliac
city: Paris cédex 13
country: France
facility: 248.604.3302A Hôpital Pitié Salpétrière
city: Pessac cédex
country: France
facility: 248.604.3305B Hôpital du Haut Levêque
city: Berlin (Hellersdorf)
country: Germany
facility: 248.604.4903 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.604.4902 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.604.4904 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.604.4905 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.604.4906 Boehringer Ingelheim Investigational Site
city: Chemnitz
country: Germany
facility: 248.604.4909 Boehringer Ingelheim Investigational Site
city: Freiburg
country: Germany
facility: 248.604.4901 Boehringer Ingelheim Investigational Site
city: Kassel
country: Germany
facility: 248.604.4907 Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: 248.604.4910 Boehringer Ingelheim Investigational Site
city: Marburg
country: Germany
facility: 248.604.4908 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 248.604.4911 Boehringer Ingelheim Investigational Site
city: Carrigtwohill
country: Ireland
facility: 248.604.35305
city: Castledermot
country: Ireland
facility: 248.604.35302 Boehringer Ingelheim Investigational Site
city: Bologna
country: Italy
facility: 248.604.3901 Università degli Studi di Bologna
city: Città S. Angelo (PE)
country: Italy
facility: 248.604.3905 Casa di Cura Villa Serena
city: Pisa
country: Italy
facility: 248.604.3906 Clinica Psichiatrica
city: Roma
country: Italy
facility: 248.604.3902 IRCCS San Raffaele
city: Telese Terme (be)
country: Italy
facility: 248.604.3909 IRCCS Fondazione "Salvatore Maugeri"
city: Torino
country: Italy
facility: 248.604.3908 Azienda Sanitaria San Giovanni Battista
city: Troina (Enna)
country: Italy
facility: 248.604.3904 IRCCS Oasi Maria SS
city: Daegu
country: Korea, Republic of
facility: 248.604.82001 Boehringer Ingelheim Investigational Site
city: Incheon
country: Korea, Republic of
facility: 248.604.82003 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 248.604.82002 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 248.604.82004 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 248.604.3401
city: Madrid
country: Spain
facility: 248.604.3403
city: Madrid
country: Spain
facility: 248.604.3405
city: Oviedo
country: Spain
facility: 248.604.3407
city: San Cugat del Vallés (Barcelona)
country: Spain
facility: 248.604.3402
city: San Sebastián
country: Spain
facility: 248.604.3404 Hospital de Donostia
city: Göteborg
country: Sweden
facility: 248.604.4602 Boehringer Ingelheim Investigational Site
city: Göteborg
country: Sweden
facility: 248.604.4603 Boehringer Ingelheim Investigational Site
city: Hedemora
country: Sweden
facility: 248.604.4601 Boehringer Ingelheim Investigational Site
city: Skövde
country: Sweden
facility: 248.604.4604 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 248.604.4606 Boehringer Ingelheim Investigational Site
city: Örebro
country: Sweden
facility: 248.604.4605 Boehringer Ingelheim Investigational Site
city: Cambridge
country: United Kingdom
facility: 248.604.44004 Boehringer Ingelheim Investigational Site
city: Chorley
country: United Kingdom
facility: 248.604.44006 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 248.604.44001 Boehringer Ingelheim Investigational Site
city: Manchester
country: United Kingdom
facility: 248.604.44007 Boehringer Ingelheim Investigational Site
city: Reading
country: United Kingdom
facility: 248.604.44009 Boehringer Ingelheim Investigational Site
city: Romford
country: United Kingdom
facility: 248.604.44002 Boehringer Ingelheim Investigational Site
city: West Green, Crawley
country: United Kingdom
facility: 248.604.44005 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.