Restless Legs Syndrome (RLS)
Conditions
Brief summary
The purpose of this study was to evaluate the safety of 2 dosage regimens of Intravenous (IV) iron Ferric Carboxymaltose (FCM) in comparison to placebo in patients with Restless Legs Syndrome (RLS)
Interventions
DRUGPlacebo
Sponsors
American Regent, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects \> or = to 18 years old, and able to give informed consent to the study. * RLS signs and symptoms affirming diagnosis. The IRLS Diagnostic Criteria for RLS must be met. * Subjects have RLS symptoms \> or = to 5 nights per week for at least the past 3 months. * A baseline score \> or = to 15 on the IRLS Rating Scale. * At least one leg with an average baseline Periodic Leg Movement while asleep (PLMS) \> or = to 15 movements per hour and at least 3 days of baseline PLMS data is measurable in each leg. * Subjects on anti-depressants, sleep medications, dopamine agonists, benzodiazepines, narcotics or other RLS treatments must be off therapy at least one week or 5 half lives, whichever is longer before any baseline RLS assessments and PLM measurements 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
* RLS 2° to other CNS disease or injury. Such disorders include peripheral neuropathy, neurodegenerative disorders, and multiple sclerosis. * RLS 2° to Chronic Kidney Disease. * Any pain related or sleep related disorders (e.g. sleep apnea) which may confound the outcome measures. * History of neuroleptic akathisia. * Oral iron use (including multivitamins with iron) after screening. * Parenteral iron use within 4 weeks prior to screening. * Parenteral iron use \> 125 mg per week within 4 to 8 weeks prior to screening. * History of \> or = to 10 blood transfusions in the past 2 years. * Anticipated need for blood transfusion during the study. * Known hypersensitivity reaction to any component to FCM. * Previously participated in an FCM clinical trial. * Chronic or serious active severe infection. * Malignancy (other than basal or squamous cell skin cancer or the subject has been cancer free for \> 5 years). * Active inflammatory arthritis (e.g. rheumatoid arthritis, SLE). * Receiving prescription medication for the treatment of bronchospasm. * Pregnant or lactating women. * Severe peripheral vascular disease with significant skin changes. * Seizure disorder currently being treated with medication. * Baseline ferritin \> 300 ng/mL. * Baseline TSAT \> or = to 45%. * History of hemochromatosis or hemosiderosis or other iron storage disorders. * AST or ALT greater than the upper limit of normal. * Hemoglobin greater than the upper limit of normal. * Calcium or phosphorous outside the normal range. * Known positive hepatitis B antigen (HBsAg) or hepatitis C viral antibody (HCV) with evidence of active hepatitis. * Known positive HIV-1/HIV-2 antibodies (anti-HIV). * Received an investigational drug within 30 days before randomization. * Chronic alcohol or drug abuse within the past 6 months. * Significant cardiovascular disease, including myocardial infarction within 12 months prior to study inclusion, congestive heart failure NYHA (New York Heart Association) III or IV, or poorly controlled hypertension according to the judgment of the investigator. * Any other pre-existing laboratory abnormality, medical condition or disease which in view of the investigator participation in this study may put the subject at risk. * Subject unable to comply with study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| International Restless Legs Syndrome (IRLS) Total Score | Change from Baseline to Day 28 | The scale represents the patients symptoms of RLS. The patient rates his/her symptoms based on 10 questions with a maximum possible score of 40 representing the most severe symptoms while a score of 0 represents no symptoms at all. |
Participant flow
Recruitment details
Study Period: March 23, 2006 to July 16, 2007 Locations: Hospitals and Medical Clinics (15 total sites)
Participants by arm
| Arm | Count |
|---|---|
| Ferric Carboxymaltose (FCM) 2 x 500 mg 500mg intravenous (IV) dose of FCM on Day 0 and Day 5. | 24 |
| Placebo Intravenous (IV) solution of placebo on Day 0 and Day 5. | 21 |
| Total | 45 |
Baseline characteristics
| Characteristic | Placebo | Ferric Carboxymaltose (FCM) 2 x 500 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 4 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 20 Participants | 35 Participants |
| Age, Continuous | 54.1 years STANDARD_DEVIATION 13.68 | 49.5 years STANDARD_DEVIATION 11.42 | 51.7 years STANDARD_DEVIATION 12.59 |
| Region of Enrollment United States | 21 participants | 24 participants | 45 participants |
| Sex: Female, Male Female | 11 Participants | 17 Participants | 28 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 24 | 6 / 21 |
| serious Total, serious adverse events | 0 / 24 | 0 / 21 |
Outcome results
Primary
International Restless Legs Syndrome (IRLS) Total Score
The scale represents the patients symptoms of RLS. The patient rates his/her symptoms based on 10 questions with a maximum possible score of 40 representing the most severe symptoms while a score of 0 represents no symptoms at all.
Time frame: Change from Baseline to Day 28
Population: Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferric Carboxymaltose (FCM) 2 x 500 mg | International Restless Legs Syndrome (IRLS) Total Score | -8.9 Scores on a scale | Standard Deviation 8.52 |
| Placebo | International Restless Legs Syndrome (IRLS) Total Score | -4.0 Scores on a scale | Standard Deviation 0.04 |