as per GCP sponsor/company decision

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.

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.

Inclusion Criteria:

1. Age ≥ 18 years
2. Diagnosis of RLS based upon the CH-RLSq and HTDI
3. IRLS score ≥ 15 at baseline evaluation when off RLS medications
4. Willingness to participate and signing the informed consent form

Exclusion Criteria:

1. S-ferritin > 300 ng/mL and/or TfS > 50 %
2. Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis and haemo-siderosis)
3. Known hypersensitivity to IV iron or any excipients in the investigational drug prod-ucts
4. 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
5. History of active asthma within the last 5 years
6. Decompensated liver cirrhosis or active hepatitis (defined as ASAT or ALAT > 3 times upper limit of normal)
7. Active acute or chronic infections (assessed by clinical judgement supplied with WBC and CRP)
8. Rheumatoid arthritis with symptoms or signs of active inflammation
9. Pregnant or nursing women
10. Previous IV iron treatment for RLS
11. IV iron treatment within 1 year prior to screening
12. Blood transfusion within 4 weeks prior to screening
13. Planned elective surgery during the study
14. Participation in any other interventional study where the study drug has not passed 5 half-lives prior to the screening
15. 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