Clinical trial NCT00375284: A 6 Week Trial to Study the Efficacy and Safety of a Starting Dose 0.25 mg Pramipexole (Mirapex) in Patients With RLS
Official title: A Phase IV Randomised, Double-blind, Active and Placebo-controlled, 6-week Trial to Investigate the Efficacy and Safety of a Starting (and Fixed) Dose 0.25 mg Pramipexole (Mirapex®) in 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: 2006-09-12
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: This trial is a 6-week, double-blind, randomized, active and placebo-controlled parallel-group study with a primary objective of comparison of starting doses of pramipexole fixed-dose (0.25 mg daily) and pramipexole titrated-dose (0.125 mg qd for 1 week, then 0.25 mg qd for the remaining 5 weeks) with placebo to evaluate efficacy and safety in treating RLS symptoms in patients diagnosed with idiopathic RLS.

The secondary objectives of this study will be to assess the onset of action of symptomatic relief of RLS for pramipexole with daily assessment of PGI and modified IRLS during two intervals of the first 2 weeks (Days 2, 3 and 4 and Days 9, 10, and 11) and assessment of IRLS, PGI and CGI-I at Weeks 1, 2, 4 and 6 (CGI-I additionally on Day 3).


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 18 to 80 years of age.
3. Diagnosis of idiopathic RLS according to the clinical RLS criteria revised by the IRLSSG in collaboration with the U.S.A. National Institutes of Health \[P03-03355\]. 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.
5. IRLS rating scale score \>15 at baseline (Visit 2).

Exclusion Criteria:

1. Women of child-bearing potential (i.e., premenopausal women, or postmenopausal women less than 6 months after last menses) who do not use during the clinical trial an adequate method of contraception such as: double barrier protection (e.g., diaphragm or condom and spermicide), intrauterine device, hormonal therapy (oral, injectable, or subcutaneous), or partners surgical sterilization.
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 as follows:

   * Any intake of dopamine agonists within 14 days prior to baseline (Visit 2).
   * Any intake of L-dopa within 14 days prior to baseline (Visit 2).
   * Any intake of L-dopa prior to baseline visit, if augmentation in RLS symptoms was observed.
   * Unsuccessful prior treatment with non-ergot dopamine agonists (e.g., pramipexole, ropinirole).
5. All treatment less than 14 days before baseline (Visit 2) or concomitant treatment with medication or dietary supplements which could significantly influence RLS symptoms, e.g., dopaminergic (other than levodopa and dopamine agonists) or antidopaminergic drugs, non-selective MAO inhibitors, sympathomimetics, neuroleptics, antidepressants, hypnotics, any benzodiazepines, antiepileptics, opioids, clonidine, ferrous salts, magnesium, folic acid, vitamin B12, antihistaminics, lithium, metoclopramide.
6. Withdrawal symptoms of any medication must not be present at baseline (Visit 2).
7. Previous 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. Confirmed diagnosis of diabetes mellitus requiring insulin therapy.
10. Any of the following lab results at screening:

    * Patients with any clinically significant abnormalities in laboratory parameters at screening at the investigators discretion.
    * Haemoglobin (Hb) below lower limit of normal (LLN).

Primary outcomes:
measure: The co-primary endpoints are: Assessment of clinical response of treatment measured by the change from baseline in total IRLS score and CGI-I responder rate (at least much improved) after 6 weeks, 2 weeks and 1 week.
timeFrame: 6 weeks
Secondary outcomes:
measure: Onset of action on Day 3 as measured by the CGI-I responder rate Onset of action as measured by PGI and modified IRLS score Clinical Global Impression of improvement Patient Global Impression IRLS as a responder rate VAS score for pain in limbs
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 248.616.065 Boehringer Ingelheim Investigational Site
state: Alabama
city: Dothan
country: United States
facility: 248.616.028 Boehringer Ingelheim Investigational Site
state: Alabama
city: Mesa
country: United States
facility: 248.616.035 Boehringer Ingelheim Investigational Site
state: Arizona
city: Peoria
country: United States
facility: 248.616.025 Boehringer Ingelheim Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: 248.616.073 Boehringer Ingelheim Investigational Site
state: Arizona
city: Tucson
country: United States
facility: 248.616.067 Boehringer Ingelheim Investigational Site
state: Arizona
city: Fayetteville
country: United States
facility: 248.616.009 Boehringer Ingelheim Investigational Site
state: Arkansas
city: Foothill Ranch
country: United States
facility: 248.616.040 Boehringer Ingelheim Investigational Site
state: California
city: Fullerton
country: United States
facility: 248.616.062 Boehringer Ingelheim Investigational Site
state: California
city: Pasadena
country: United States
facility: 248.616.050 Boehringer Ingelheim Investigational Site
state: California
city: Colorado Springs
country: United States
facility: 248.616.031 Boehringer Ingelheim Investigational Site
state: Colorado
city: Pueblo
country: United States
facility: 248.616.017 Boehringer Ingelheim Investigational Site
state: Colorado
city: Wallingford
country: United States
facility: 248.616.071 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Deland
country: United States
facility: 248.616.043 Boehringer Ingelheim Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: 248.616.014 Boehringer Ingelheim Investigational Site
state: Florida
city: Naples
country: United States
facility: 248.616.020 Boehringer Ingelheim Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: 248.616.048 Boehringer Ingelheim Investigational Site
state: Florida
city: Spring Hill
country: United States
facility: 248.616.072 Boehringer Ingelheim Investigational Site
state: Florida
city: St. Petersburg
country: United States
facility: 248.616.018 Boehringer Ingelheim Investigational Site
state: Florida
city: Augusta
country: United States
facility: 248.616.049 Boehringer Ingelheim Investigational Site
state: Georgia
city: Columbus
country: United States
facility: 248.616.033 Boehringer Ingelheim Investigational Site
state: Georgia
city: Macon
country: United States
facility: 248.616.057 Boehringer Ingelheim Investigational Site
state: Georgia
city: Savannah
country: United States
facility: 248.616.066 Boehringer Ingelheim Investigational Site
state: Georgia
city: Stockbridge
country: United States
facility: 248.616.047 Boehringer Ingelheim Investigational Site
state: Georgia
city: Chicago
country: United States
facility: 248.616.059 Boehringer Ingelheim Investigational Site
state: Illinois
city: Lenexa
country: United States
facility: 248.616.045 Boehringer Ingelheim Investigational Site
state: Kansas
city: Olathe
country: United States
facility: 248.616.061 Boehringer Ingelheim Investigational Site
state: Kansas
city: Baton Rouge
country: United States
facility: 248.616.060 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Brighton
country: United States
facility: 248.616.058 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Wellesley Hills
country: United States
facility: 248.616.051 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Minneapolis
country: United States
facility: 248.616.001 Boehringer Ingelheim Investigational Site
state: Minnesota
city: Jackson
country: United States
facility: 248.616.004 Boehringer Ingelheim Investigational Site
state: Mississippi
city: Florissant
country: United States
facility: 248.616.064 Boehringer Ingelheim Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: 248.616.016 Boehringer Ingelheim Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: 248.616.063 Boehringer Ingelheim Investigational Site
state: Missouri
city: Dover
country: United States
facility: 248.616.053 Boehringer Ingelheim Investigational Site
state: New Hampshire
city: Albuquerque
country: United States
facility: 248.616.036 Boehringer Ingelheim Investigational Site
state: New Mexico
city: Albany
country: United States
facility: 248.616.021 Boehringer Ingelheim Investigational Site
state: New York
city: Cincinnati
country: United States
facility: 248.616.013 Boehringer Ingelheim Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: 248.616.003 Boehringer Ingelheim Investigational Site
state: Ohio
city: Marion
country: United States
facility: 248.616.068 Boehringer Ingelheim Investigational Site
state: Ohio
city: Norman
country: United States
facility: 248.616.012 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: 248.616.006 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: 248.616.019 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Clarks Summit
country: United States
facility: 248.616.069 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Columbia
country: United States
facility: 248.616.008 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Dallas
country: United States
facility: 248.616.005 Boehringer Ingelheim Investigational Site
state: Texas
city: Rockwall
country: United States
facility: 248.616.070 Boehringer Ingelheim Investigational Site
state: Texas
city: San Marcos
country: United States
facility: 248.616.039 Boehringer Ingelheim Investigational Site
state: Texas
city: Alexandria
country: United States
facility: 248.616.011 Boehringer Ingelheim Investigational Site
state: Virginia
city: Norfolk
country: United States
facility: 248.616.055 Boehringer Ingelheim Investigational Site
state: Virginia
city: Milwaukee
country: United States
facility: 248.616.024 Boehringer Ingelheim Investigational Site
state: Wisconsin
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: