Restless Legs Syndrome
Conditions
Brief summary
Non-randomized open label Phase II clinical trial in which subjects meeting criteria for RLS were assigned to 1 of 3 treatment cohorts. The first cohort received one 500 mg IV iron sucrose infusion in 500 mL normal sterile saline (NSS) administered over four hours. The second cohort received two 500 mg IV iron sucrose infusions in 500mL of NSS administered over four to six hours on two separate dates, separated by two to seven days. The third cohort received two 500 mg IV iron sucrose infusions in at least 500 mL of NSS over six hours within 30 hours of the start of the first infusion. Cohorts were enrolled and treated subsequently.
Sponsors
American Regent, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed consent. * Male or female subjects \> 18 yrs. old. * RLS signs and symptoms affirming diagnosis. * A baseline score \> or = to 15 is required on the International RLS Study Group Rating Scale (IRLSSG). * At least one leg with an average baseline Periodic Leg Movement (PLM) while asleep \> or = to 15 movements per hour by actigraphy. * Subjects on dopa-adrenergic therapy or other RLS treatments must be off therapy at least one week before any baseline RLS assessments and actigraphy measurement are obtained. * Subject has regular sleep hours between 9 p.m. and 9 a.m. * Subjects at risk for pregnancy must have a negative pregnancy test at baseline and be practicing an acceptable form of birth control.
Exclusion criteria
* Known intolerance to Venofer. * RLS which is ascribed to renal disease. * RLS 2° to other CNS disease or injury. * Any pain related or sleep related disorders which may confound the outcome measures. * History of neuroleptic akinesia. * Concurrent use of oral iron supplement. * Parenteral iron use within the past 6 months. * Active infection. * Currently being treated for asthma. * Severe peripheral vascular disease with significant skin changes. * Seizure disorder currently being treated with medication. * Serum ferritin level \> 300 ng/mL or a TSAT \> or = to 45% at baseline or a history of hemochromatosis. * Significant cardiovascular or hepatic disease or any other pre-existing medical condition or disease which in the view of the investigator participation in this study would put the subject's disease management at risk or the subject would be unable to comply with the study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Day 84 for International Restless Leg Syndrome Study Group (IRLSSG) Scale | Baseline to Day 84 | Validated rating scale of RLS symptoms (Range 1 \[mild\] - 40 \[severe\]) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Day 84 for Total Periodic Limb Movements (PLM's) | Baseline to Day 84 | Quantifies amount of leg movement |
Participant flow
Recruitment details
November 14, 2003 - August 8, 2005 Locations: Hospitals and Medical Clinics
Pre-assignment details
A Baseline score \> or = to 15 was required on the International RLS Study Group (IRLSSG) Rating Scale. At least 1 leg was required to have an average baseline Periodic Leg Movement (PLM) while asleep \> or = to 15 movements per hour by actigraphy.
Participants by arm
| Arm | Count |
|---|---|
| Cohort I (Venofer 500mg x 1 Dose) Single 500 mg infusion of Venofer over 4 hours. | 7 |
| Cohort II (Venofer 500mg X 2 Doses) A 500 mg infusion of Venofer over 4 to 6 hours on Day 0; with a second 500 mg infusion administered between Day 2 and Day 7. | 6 |
| Cohort III (Venofer 500mg x 2 Doses) A 500 mg infusion of Venofer over 6 hours on Day 0, followed within 24 hours by a second 500 mg infusion of Venofer over 6 hours. | 8 |
| Total | 21 |
Baseline characteristics
| Characteristic | Cohort I (Venofer 500mg x 1 Dose) | Cohort II (Venofer 500mg X 2 Doses) | Cohort III (Venofer 500mg x 2 Doses) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 7 | 4 / 6 | 5 / 8 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 | 1 / 8 |
Outcome results
Primary
Mean Change From Baseline to Day 84 for International Restless Leg Syndrome Study Group (IRLSSG) Scale
Validated rating scale of RLS symptoms (Range 1 \[mild\] - 40 \[severe\])
Time frame: Baseline to Day 84
Population: Only subjects who completed the IRLSSG Rating Scale at baseline AND on Day 84.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort I (Venofer 500mg x 1 Dose) | Mean Change From Baseline to Day 84 for International Restless Leg Syndrome Study Group (IRLSSG) Scale | -2.4 units on a scale | Standard Deviation 5.41 |
| Cohort II (Venofer 500mg X 2 Doses) | Mean Change From Baseline to Day 84 for International Restless Leg Syndrome Study Group (IRLSSG) Scale | -14.3 units on a scale | Standard Deviation 5.03 |
| Cohort III (Venofer 500mg x 2 Doses) | Mean Change From Baseline to Day 84 for International Restless Leg Syndrome Study Group (IRLSSG) Scale | -16.0 units on a scale | Standard Deviation 8.49 |
Secondary
Mean Change From Baseline to Day 84 for Total Periodic Limb Movements (PLM's)
Quantifies amount of leg movement
Time frame: Baseline to Day 84
Population: Only subjects who recorded PLM's/Hour at Baseline AND on Day 84.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort I (Venofer 500mg x 1 Dose) | Mean Change From Baseline to Day 84 for Total Periodic Limb Movements (PLM's) | -7.2 PLM's per hour | Standard Deviation 24.12 |
| Cohort II (Venofer 500mg X 2 Doses) | Mean Change From Baseline to Day 84 for Total Periodic Limb Movements (PLM's) | -75.0 PLM's per hour | Standard Deviation 49.71 |
| Cohort III (Venofer 500mg x 2 Doses) | Mean Change From Baseline to Day 84 for Total Periodic Limb Movements (PLM's) | -96.2 PLM's per hour | Standard Deviation 0 |
Post Hoc
Percentage (%) of Subjects Responding to Treatment From Baseline to Day 84 Based on Global Assessments by the Examiner.
Response is defined as any effect based on a scale of 0 through 4 where 0 = no effect, 1 = mild effect, 2 = moderate effect, 3 = marked effect, and 4 = dramatic effect.
Time frame: Baseline to Day 84
Population: Only subjects who were evaluated at Baseline AND on Day 84
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I (Venofer 500mg x 1 Dose) | Percentage (%) of Subjects Responding to Treatment From Baseline to Day 84 Based on Global Assessments by the Examiner. | 28.6 percent of participants |
| Cohort II (Venofer 500mg X 2 Doses) | Percentage (%) of Subjects Responding to Treatment From Baseline to Day 84 Based on Global Assessments by the Examiner. | 66.7 percent of participants |
| Cohort III (Venofer 500mg x 2 Doses) | Percentage (%) of Subjects Responding to Treatment From Baseline to Day 84 Based on Global Assessments by the Examiner. | 66.7 percent of participants |