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

Idiopathic Restless Legs Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00390689
• Other study ID #: 248.627
• Status: Completed
• Phase: Phase 3
• First received: October 19, 2006
• Last updated: June 23, 2014
• Start date: October 2006

Study information

• Verified date: April 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Idiopathic Restless Legs Syndrome
• Psychomotor Agitation
• Restless Legs Syndrome

Intervention

Drug:
• Pramipexole 0.125 mg tablet

• Pramipexole 0.5 mg tablet

Locations

Country	Name	City	State
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	248.627.023 Boehringer Ingelheim Investigational Site	Kitakyusyu, Fukuoka
Japan	248.627.024 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	248.627.038 Boehringer Ingelheim Investigational Site	Koriyama, Fukushima
Japan	248.627.041 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	248.627.010 Boehringer Ingelheim Investigational Site	Sapporo, Hokkaido
Japan	248.627.035 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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in International Restless Legs Syndrome (IRLS) Total Score at 6 Weeks	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.	Week 6 - change from baseline	No
Secondary	IRLS Responder	The percentage of patients with 50 % or more reduction of IRLS (The measure means the percentage of high responder on the trial medications)	baseline to week 6	No
Secondary	Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Total Score at 6 Weeks	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).	Week 6 - change from baseline	No
Secondary	Change From Baseline in Japanese Version of the Epworth Sleepiness Scale (JESS) Total Score at 6 Weeks	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)	Week 6 - change from baseline	No
Secondary	Clinical Global Impression Global Improvement (CGI-I) Responder	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.	baseline to week 6	No
Secondary	Patient Global Impression (PGI) Responder	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.	baseline to week 6	No
Secondary	Clinically Significant Abnormalities in Vital Signs (Blood Pressure and Pulse Rate in Both Supine and Standing Positions), ECG, Laboratory Tests - Double Blind Period.		baseline to 6 weeks	Yes
Secondary	Change From Baseline in International Restless Legs Syndrome (IRLS) Total Score at 52 Weeks for Open-Label Period	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).	Week 52 - change from baseline	No
Secondary	IRLS Responder for Open-label Period	The percentage of patients with 50 % or more reduction of IRLS (The measure means the percentage of high responder on the trial medications)	baseline to week 52	No
Secondary	Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Total Score at 52 Weeks for Open-Label Period	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).	Week 52 - change from baseline	No
Secondary	Change From Baseline in Japanese Version of the Epworth Sleepiness Scale (JESS) Total Score at 52 Weeks for Open-Label Period	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)	Week 52 - change from baseline	No
Secondary	Clinical Global Impression Global Improvement (CGI-I) Responder at 52 Weeks for Open-label Period	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.	baseline to week 52	No
Secondary	Patient Global Impression (PGI) Responder at 52 Weeks for Open-Label Period	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.	baseline to week 52	No
Secondary	Possible Augmentation in RLS Symptoms at 52 Weeks for Open-Label Period	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	baseline to week 52	No

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