A Randomised, Comparing Fixed Doses of Pramipexole to Investigate the Efficacy and Safety in Patients With RLS.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00390689
First received: October 19, 2006
Last updated: June 23, 2014
Last verified: April 2014
  Purpose

The objective of double blind phase in this trial is to compare the efficacy and safety at the fixed dose of 0.25 mg,0.5 mg and 0.75 mg pramipexole in RLS. The objective of open label phase in this trial is to investigate the long term safety and efficacy of pramipexole in RLS.


Condition Intervention Phase
Idiopathic Restless Legs Syndrome
Drug: Pramipexole 0.125 mg tablet
Drug: Pramipexole 0.5 mg tablet
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind Study to Evaluate the Efficacy and Safety of Pramipexole at Fixed Doses of 0.25 mg, 0.5 mg, and 0.75 mg in Patients With Idiopathic Restless Legs Syndrome for 6 Weeks, Followed by a 46-week Open-label Long-term Study

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change From Baseline in International Restless Legs Syndrome (IRLS) Total Score at 6 Weeks [ Time Frame: Week 6 - change from baseline ] [ Designated as safety issue: No ]
    The International Restless Legs Syndrome Study Group (IRLSSG) proposes classification of severity based on the total score on the IRLS (0-10, mild; 11-20, moderate; 21-30, severe; 31-40, very severe). A decrease in the score of the IRLS by 10 or more points corresponds to the improvement of severity by one rank and has clinical importance. Therefore, the primary endpoint in the double-blind period was set as a decrease by 10 or more points in the mean change on the total score of the IRLS from the baseline to Visit 5 (last observation day in the double-blind period) at all doses of 0.25 mg, 0.5 mg, and 0.75 mg/day of pramipexole.


Secondary Outcome Measures:
  • IRLS Responder [ Time Frame: baseline to week 6 ] [ Designated as safety issue: No ]
    The percentage of patients with 50 % or more reduction of IRLS (The measure means the percentage of high responder on the trial medications)

  • Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Total Score at 6 Weeks [ Time Frame: Week 6 - change from baseline ] [ Designated as safety issue: No ]
    PSQI developed to evaluate the quality of sleep is a self-recording questionnaire consisting of 18 questions focused on 7 factors such as sleep quality, sleep period time, sleep latency, sleep efficiency, sleep difficulty, use of hypnotics, and hindrance to activities of daily living due to daytime sleepiness. Each score (0-3 points) in the respective factors was added to calculate the total score (0-21 points). Rating scale scored from 0 (best sleep) to 21 (worst sleep).

  • Change From Baseline in Japanese Version of the Epworth Sleepiness Scale (JESS) Total Score at 6 Weeks [ Time Frame: Week 6 - change from baseline ] [ Designated as safety issue: No ]
    ESS is a self-recording scale used to evaluate sleepiness experienced in daily activities and it consists of 8 items focused on specific situations such as reading books and watching television. Each score (0-3 points) to 8 questions was added simply to calculate the total ESS score. A Japanese translation of the ESS (a provisional version provided by the Japanese Respiratory Society) used so far had not been prepared through the international scale development and validation process, but the version prepared through this process was published at the 31st meeting of the Japanese Society of Sleep Research. The questions in JESS had been discussed with the original author of the ESS and their measurement concepts had been confirmed. The JESS is the Japanese version of ESS prepared through the international scale development and validation process. Rating scale scored from 0 (no daytime sleep) to 24 (worst daytime sleep)

  • Clinical Global Impression Global Improvement (CGI-I) Responder [ Time Frame: baseline to week 6 ] [ Designated as safety issue: No ]
    CGI is extensively used for risk-benefit evaluation (efficacy) of drug therapies. The CGI evaluates the severity and improvement in 7 ranks. It also evaluates the therapeutic effect and side effects in 4 ranks, separately. Rating scale from 1 (very much improved) to 7 (very much worse). The percentage of patients who were evaluated as 1(very much improved) or 2(much improved) by the investigator were considered responders.

  • Patient Global Impression (PGI) Responder [ Time Frame: baseline to week 6 ] [ Designated as safety issue: No ]
    PGI is used to evaluate a global impression by patients themselves in 7 ranks. Rating scale from 1 (very much better) to 7 (very much worse). The percentage of patients where the patient evaluated himself/herself as 1(very much better) or 2(much better)were considered responders.

  • Clinically Significant Abnormalities in Vital Signs (Blood Pressure and Pulse Rate in Both Supine and Standing Positions), ECG, Laboratory Tests - Double Blind Period. [ Time Frame: baseline to 6 weeks ] [ Designated as safety issue: Yes ]
  • Change From Baseline in International Restless Legs Syndrome (IRLS) Total Score at 52 Weeks for Open-Label Period [ Time Frame: Week 52 - change from baseline ] [ Designated as safety issue: No ]
    The International Restless Legs Syndrome Study Group (IRLSSG) proposes classification of severity based on the total score on the IRLS (0-10, mild; 11-20, moderate; 21-30, severe; 31-40, very severe).

  • IRLS Responder for Open-label Period [ Time Frame: baseline to week 52 ] [ Designated as safety issue: No ]
    The percentage of patients with 50 % or more reduction of IRLS (The measure means the percentage of high responder on the trial medications)

  • Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Total Score at 52 Weeks for Open-Label Period [ Time Frame: Week 52 - change from baseline ] [ Designated as safety issue: No ]
    PSQI developed to evaluate the quality of sleep is a self-recording questionnaire consisting of 18 questions focused on 7 factors such as sleep quality, sleep period time, sleep latency, sleep efficiency, sleep difficulty, use of hypnotics, and hindrance to activities of daily living due to daytime sleepiness. Each score (0-3 points) in the respective factors was added to calculate the total score (0-21 points). Rating scale scored from 0 (best sleep) to 21 (worst sleep).

  • Change From Baseline in Japanese Version of the Epworth Sleepiness Scale (JESS) Total Score at 52 Weeks for Open-Label Period [ Time Frame: Week 52 - change from baseline ] [ Designated as safety issue: No ]
    ESS is a self-recording scale used to evaluate sleepiness experienced in daily activities and it consists of 8 items focused on specific situations such as reading books and watching television. Each score (0-3 points) to 8 questions was added simply to calculate the total ESS score. A Japanese translation of the ESS (a provisional version provided by the Japanese Respiratory Society) used so far had not been prepared through the international scale development and validation process, but the version prepared through this process was published at the 31st meeting of the Japanese Society of Sleep Research. The questions in JESS had been discussed with the original author of the ESS and their measurement concepts had been confirmed. The JESS is the Japanese version of ESS prepared through the international scale development and validation process. Rating scale scored from 0 (no daytime sleep) to 24 (worst daytime sleep)

  • Clinical Global Impression Global Improvement (CGI-I) Responder at 52 Weeks for Open-label Period [ Time Frame: baseline to week 52 ] [ Designated as safety issue: No ]
    CGI is extensively used for risk-benefit evaluation (efficacy) of drug therapies. The CGI evaluates the severity and improvement in 7 ranks. It also evaluates the therapeutic effect and side effects in 4 ranks, separately. Rating scale from 1 (very much improved) to 7 (very much worse). The percentage of patients who were evaluated as 1(very much improved) or 2(much improved) by the investigator were considered responders.

  • Patient Global Impression (PGI) Responder at 52 Weeks for Open-Label Period [ Time Frame: baseline to week 52 ] [ Designated as safety issue: No ]
    PGI is used to evaluate a global impression by patients themselves in 7 ranks. Rating scale from 1 (very much better) to 7 (very much worse). The percentage of patients where the patient evaluated himself/herself as 1(very much better) or 2(much better)were considered responders.

  • Possible Augmentation in RLS Symptoms at 52 Weeks for Open-Label Period [ Time Frame: baseline to week 52 ] [ Designated as safety issue: No ]
    Possible augmentation defined as persistence of a state in which RLS symptoms begin to occur 2 hours earlier than the usual time zone for 5 days or more a week


Enrollment: 154
Study Start Date: October 2006
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pramipexole 0.25 mg once daily
Pramipexole 0.25 mg given once daily
Drug: Pramipexole 0.125 mg tablet
Experimental: Pramipexole 0.5 mg once daily
Pramipexole 0.5 mg given once daily
Drug: Pramipexole 0.5 mg tablet
Experimental: Pramipexole 0.75 mg once daily
Pramipexole 0.75 mg given once daily
Drug: Pramipexole 0.125 mg tablet Drug: Pramipexole 0.5 mg tablet

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients between 20 and 80 years
  2. Patients with a diagnosis of restless legs syndrome (RLS) according to the following diagnosis criteria of National institute of health (NIH)/International restless legs syndrome study group (IRLSSG):

    1. An urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs.
    2. The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting.
    3. 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.
    4. 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.
  3. Patients with a total score larger than 15 on the IRLS at Visit 2

Exclusion Criteria:

  1. Premenopausal women who meet any of the following 1) to 3) 1) Patients who are pregnant or possibly pregnant 2) Patients who are lactating 3) Patients who wish to become pregnant during the study period
  2. Patients who cannot take adequate contraceptive measures
  3. Patients with a history of akathisia induced by neuroleptics
  4. Patients with diabetes mellitus requiring insulin therapy
  5. Patients who are judged to have microcytic anaemia by the investigator or sub-investigator
  6. Patients with a history or signs of peripheral neuropathy, myelopathy, multiple sclerosis, Parkinson's disease or other neurological diseases that may result in the occurrence of secondary RLS in the physical function tests or neurological tests
  7. Patients with other sleep disorders such as abnormal behaviour during Rapid eye movement (REM) sleep, narcolepsy and sleep apnoea syndrome (patients with an apnoea-hypopnoea index (AHI) exceeding 15 determined by polysomnography at the relevant trial site or those with loud snoring at least 5 nights/week and an experience of respiratory arrest during sleep or excessive daytime sleepiness)
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00390689

Locations
Japan
248.627.037 Boehringer Ingelheim Investigational Site
Aichi-gun, Aichi, Japan
248.627.014 Boehringer Ingelheim Investigational Site
Fujisawa, Kanagawa, Japan
248.627.029 Boehringer Ingelheim Investigational Site
Fukuoka, Fukuoka, Japan
248.627.032 Boehringer Ingelheim Investigational Site
Hiroshima, Hiroshima, Japan
248.627.030 Boehringer Ingelheim Investigational Site
Kagoshima, Kagoshima, Japan
248.627.013 Boehringer Ingelheim Investigational Site
Kanagawa, Yokohama, Japan
248.627.033 Boehringer Ingelheim Investigational Site
Kanazawa, Ishikawa, Japan
248.627.027 Boehringer Ingelheim Investigational Site
Kawasaki, Kanagawa, Japan
248.627.024 Boehringer Ingelheim Investigational Site
Kitakyusyu, Fukuoka, Japan
248.627.023 Boehringer Ingelheim Investigational Site
Kitakyusyu, Fukuoka, Japan
248.627.022 Boehringer Ingelheim Investigational Site
Kochi, Kochi, Japan
248.627.034 Boehringer Ingelheim Investigational Site
Kodaira, Tokyo, Japan
248.627.041 Boehringer Ingelheim Investigational Site
Koriyama, Fukushima, Japan
248.627.038 Boehringer Ingelheim Investigational Site
Koriyama, Fukushima, Japan
248.627.039 Boehringer Ingelheim Investigational Site
Kumamoto, Kumamoto, Japan
248.627.003 Boehringer Ingelheim Investigational Site
Kurume, Fukuoka, Japan
248.627.036 Boehringer Ingelheim Investigational Site
Minato-ku, Tokyo, Japan
248.627.025 Boehringer Ingelheim Investigational Site
Mitaka-shi, Tokyo, Japan
248.627.015 Boehringer Ingelheim Investigational Site
Nagoya, Aichi, Japan
248.627.017 Boehringer Ingelheim Investigational Site
Osaka, Osaka, Japan
248.627.011 Boehringer Ingelheim Investigational Site
Otaru, Hokkaido, Japan
248.627.026 Boehringer Ingelheim Investigational Site
Otsu, Shiga, Japan
248.627.002 Boehringer Ingelheim Investigational Site
Sakai,Osaka, Japan
248.627.035 Boehringer Ingelheim Investigational Site
Sapporo, Hokkaido, Japan
248.627.010 Boehringer Ingelheim Investigational Site
Sapporo, Hokkaido, Japan
248.627.012 Boehringer Ingelheim Investigational Site
Sendai, Miyagi, Japan
248.627.001 Boehringer Ingelheim Investigational Site
Shibuya-ku, Tokyo, Japan
248.627.004 Boehringer Ingelheim Investigational Site
Shimotsuga-gun,Tochigi, Japan
248.627.040 Boehringer Ingelheim Investigational Site
Shinjuku-ku, Tokyo, Japan
248.627.018 Boehringer Ingelheim Investigational Site
Takatsuki,Osaka, Japan
248.627.028 Boehringer Ingelheim Investigational Site
Tokorozawa, Saitama, Japan
248.627.019 Boehringer Ingelheim Investigational Site
Tokushima, Tokushima, Japan
248.627.016 Boehringer Ingelheim Investigational Site
Toyohashi, Aichi, Japan
248.627.031 Boehringer Ingelheim Investigational Site
Urasoe, Okinawa, Japan
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00390689     History of Changes
Other Study ID Numbers: 248.627
Study First Received: October 19, 2006
Results First Received: March 5, 2009
Last Updated: June 23, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Restless Legs Syndrome
Psychomotor Agitation
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases
Parasomnias
Mental Disorders
Dyskinesias
Neurologic Manifestations
Psychomotor Disorders
Neurobehavioral Manifestations
Signs and Symptoms
Pramipexol
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on July 29, 2014