IV Iron Treatment of Restless Legs Syndrome

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to to establish proof-of-concept for efficacy of iron isomaltoside 1000 in subjects with Restless Legs Syndrome. The study is a randomised, comparative, double-blind study with a 3 months extension. Subjects with restless leg syndrome (RLS) will be randomised 2:1 to one of the following treat-ment groups: Group A (42 subjects): 1000 mg iron isomaltoside 1000 Group B (21 subjects): Placebo infusion Furthermore, non-responders, who continue to meet entry requirements, will receive 1000 mg iron isomaltoside 1000 at week 6.

Detailed Description
-----------------
RLS is a disorder of sensation with a prevalence of around 2-5 % of the population. RLS is extremely responsive to dopaminergic agents, but a second issue is that iron deficiency states may precipitate RLS in as much as 25-30 % of subjects with iron deficiency. RLS appears to be related to deficits in brain iron content and metabolism. Magnetic resonance imaging (MRI) images demonstrate a decrease in substantia nigra and red nucleus iron content. The severity of this decrease in brain iron content is correlated with the severity of symptoms. A number of patients are quite resistant to dietary iron repletion but do resolve symptoms with high doses of intravenous (IV) iron. For the individual subject, there will be 4 phases to the study which includes teleconferences (TCs) and 2 visits. The treatment and treatment evaluation is the main study.

Official Title
-----------------
A Phase II, Six-week, Randomised, Comparative, Double-blind Study of Intravenous Iron Isomaltoside 1000 Versus Placebo in Subjects With Restless Leg Syndrome With a 3 Month Extension

Conditions
-----------------
Restless Legs Syndrome

Intervention / Treatment
-----------------
* Drug: Iron isomaltoside 1000
* Drug: Sodium Chloride 0.9%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years Diagnosis of RLS based upon the CH-RLSq and HTDI IRLS score ≥ 15 at baseline evaluation when off RLS medications Willingness to participate and signing the informed consent form Exclusion Criteria: S-ferritin > 300 ng/mL and/or TfS > 50 % Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis and haemo-siderosis) Known hypersensitivity to IV iron or any excipients in the investigational drug prod-ucts Pregnant or nursing women. In order to avoid pregnancy, women of childbearing po-tential have to use adequate contraception (e.g. intrauterine devices, hormonal contra-ceptives, or double barrier method) during the whole study period and 7 days after the last dosing History of active asthma within the last 5 years Decompensated liver cirrhosis or active hepatitis (defined as ASAT or ALAT > 3 times upper limit of normal) Active acute or chronic infections (assessed by clinical judgement supplied with WBC and CRP) Rheumatoid arthritis with symptoms or signs of active inflammation Pregnant or nursing women Previous IV iron treatment for RLS IV iron treatment within 1 year prior to screening Blood transfusion within 4 weeks prior to screening Planned elective surgery during the study Participation in any other interventional study where the study drug has not passed 5 half-lives prior to the screening Any other medical condition that, in the opinion of the Investigator, may cause the subject to be unsuitable for the completion of the study or place the subject at potential risk from being in the study, e.g. history of multiple allergies, a malignancy, uncon-trolled hypertension, unstable ischaemic heart disease, or uncontrolled diabetes melli-tus

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Infusion of 1000 mg iron isomaltoside 1000 at baseline. The infusion is diluted in 100 mL 0.9 % sodium chloride and given over approximately 15 min | Drug: Iron isomaltoside 1000<br>* Intravenous treatment<br>* Other names: Monofer;|
| Placebo Comparator: Group B<br>Infusion of 100 mL 0.9 % sodium chloride at baseline given over approximately 15 min | Drug: Sodium Chloride 0.9%<br>* Intravenous treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the change in RLS symptoms from baseline to week 6 measured by the clinical global impression (CGI) score |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in RLS symptoms from baseline to week 4 and month 2 and 3 measured by the CGI score |  | 3 months | 
| Change in RLS symptoms from baseline to week 4 and 6 and month 2 and 3 measured by the International Restless Legs Scale (IRLS) |  | from baseline to t = 12 weeks | 
| Time from baseline to start of RLS medication |  | from baseline to t = 6 weeks | 
| Time from baseline to start of RLS medication or non-response (CGI ≥ 3 at week 6) |  | from baseline to t = 6 weeks |