A Phase IV Randomised, Double-blind, Placebo-controlled, Dose Titration Trial With Pramipexole (Sifrol, Mirapexin) 0.125-0.75 mg/Day Per os to Investigate the Long-term Efficacy, Safety and Tolerability in Patients With Idiopathic Moderate to Severe Restless Legs Syndrome for 26 Weeks Followed by a 26 Week Open-label Extension Treatment Period
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 331
- 试验地点
- 42
- 主要终点
- Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Total Score After 26 Weeks
研究概览
简要总结
The primary objective of the current study will be the evaluation of long-term efficacy of a 26-weeks treatment with pramipexole in patients with idiopathic moderate to severe Restless Legs Syndrome (RLS) in comparison to placebo.
The key secondary objectives are to assess the effects on clinical global impressions - global improvement (CGI-I) (based on CGI-I responder rate) and on RLS (based on IRLS responder rate) for 26 weeks under pramipexole in comparison to placebo. Further secondary objectives are to investigate the incidence and severity of augmentation and rebound and to assess the effects on patient global impression (PGI) (based on PGI responder rate), on RLS symptoms (based on the RLS-6 scales), on associated mood disturbance (based on item 10 of the IRLS), on pain in limbs (based on a visual analogue scale (VAS)), on quality of life in RLS (based on Johns Hopkins RLS-QoL), on general quality of life Short Form 36 (SF-36) and on safety (based on adverse events (AE) profile) of pramipexole in comparison to placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent consistent with International Conference on Harmonization - Good Clinical Practice (ICH-GCP) and local Institutional Review Board/Independent Ethics Committee (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
- •Male or female out-patients aged 18-85 years
- •Diagnosis of idiopathic RLS according to the clinical RLS criteria of the International Restless Legs Syndrome Study Group (IRLSSG) [P03-03355]. All four criteria must be present to fulfil the diagnosis of RLS.
- •RLS symptoms present at least 2 to 3 days per week during the last 3 months prior to baseline (Visit 2)
- •IRLS total score >15 at baseline (Visit 2)
排除标准
- •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 partner's surgical sterilization
- •Any woman of child-bearing potential not having a negative pregnancy test at screening
- •Breastfeeding women
- •Patients with known hypersensitivity to pramipexole or any other component of the investigational product or placebo tablets
- •Diagnosis of augmentation under previous pharmacological RLS treatment
- •Concomitant or previous pharmacologic therapy as follows: Any intake of dopamine agonists within 14 days prior to baseline (Visit 2); Any intake of levodopa within 14 days prior to baseline (Visit 2); Unsuccessful prior treatment with non-ergot dopamine agonists (e.g. pramipexole, ropinirole);
研究组 & 干预措施
Placebo
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks.
干预措施: Placebo (Drug)
Pramipexole
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase or decrease the dose in steps to 0.25 mg, 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks.
干预措施: Pramipexole (Drug)
结局指标
主要结局
Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Total Score After 26 Weeks
时间窗: Baseline and 26 weeks
IRLS total score ranging from 0 (no RLS symptoms) to 40 (very severe RLS symptoms)
次要结局
- Clinical Global Impression - Global Improvement (CGI-I) Responder Rate(after 26 weeks of treatment)
- International Restless Legs Syndrome (IRLS) Study Group Rating Scale Responder Rate(after 26 weeks of treatment)
- Patient Global Impression (PGI) Responder Rate(after 26 weeks of treatment)
- Change From Baseline in Restless Legs Syndrome-6 (RLS-6) Score "Satisfaction With Sleep" After 26 Weeks(baseline and 26 weeks of treatment)
- Change From Baseline in RLS-6 Score "Severity Falling Asleep" After 26 Weeks(Baseline and 26 weeks of treatment)
- Change From Baseline in RLS-6 Score "Severity During the Night" After 26 Weeks(baseline and 26 weeks of treatment)
- Change From Baseline in RLS-6 Score "Severity During the Day When at Rest" After 26 Weeks(Baseline and 26 weeks of treatment)
- Change From Baseline RLS-6 Score "Severity During the Day Engaged in Activities" After 26 Weeks(Baseline and 26 weeks of treatment)
- Change From Baseline in RLS-6 Score "Tired or Sleepy During the Day" After 26 Weeks(Baseline and 26 weeks of treatment)
- Change From Baseline in IRLS Mood Disturbance Score (Item 10) After 26 Weeks(Baseline and 26 weeks of treatment)
- Change From Baseline in Visual Analogue Scale (VAS) Score for Pain in Limbs After 26 Weeks(Baseline and 26 weeks of treatment)
- Change From Baseline in Quality of Life in RLS (RLS QoL) Score After 26 Weeks(Baseline and 26 weeks of treatment)
- Change From Baseline in Short Form-36 (SF-36) Dimension Bodily Pain After 26 Weeks(Baseline and 26 weeks)
- Change From Baseline in SF-36 Dimension General Health After 26 Weeks(Baseline and 26 weeks)
- Change From Baseline in SF-36 Dimension Mental Health After 26 Weeks(Baseline and 26 weeks)
- Change From Baseline in SF-36 Dimension Physical Functioning After 26 Weeks(Baseline and 26 weeks)
- Change From Baseline in SF-36 Dimension Role Limitations Due to Emotional Problems After 26 Weeks(Baseline and 26 weeks)
- Change From Baseline in SF-36 Dimension Role Limitations Due to Physical Problems After 26 Weeks(Baseline and 26 weeks)
- Change From Baseline in SF-36 Dimension Social Functioning After 26 Weeks(Baseline and 26 weeks)
- Change From Baseline in SF-36 Dimension Vitality After 26 Weeks(Baseline and 26 weeks)
- Change From Baseline in SF-36 Dimension Mental Component Summary After 26 Weeks(Baseline and 26 weeks)
- Change From Baseline in SF-36 Dimension Physical Component Summary After 26 Weeks(Baseline and 26 weeks)
- Diagnosis of Classified Augmentation According to Independent Expert Panel(after at least 4 weeks of treatment)
- Worsening of RLS Symptoms (by at Least 4 Points in the IRLS Total Score Compared to Baseline) After Treatment Discontinuation(after at least 1 week of treatment discontinuation)
- Baseline, Week 26 Mean Supine Systolic Blood Pressure(Baseline, Week 26)
- Baseline, Week 26 Mean Standing Systolic Blood Pressure(Baseline, Week 26)
- Baseline, Week 26 Mean Supine Diastolic Blood Pressure(Baseline, Week 26)
- Baseline, Week 26 Mean Standing Diastolic Blood Pressure(Baseline, Week 26)
- Baseline, Week 26 Mean Standing Pulse Rate(Baseline, Week 26)
- Baseline, Week 26 Mean Supine Pulse Rate(Baseline, Week 26)