Randomized, Placebo-controlled Trial of Ferric Carboxymaltose in RLS Patients With Iron-deficiency Anemia
Condition: Restless Legs Syndrome (RLS)
MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Anemia, Iron-Deficiency; Iron Deficiencies; Syndrome
Intervention: Injectafer® (Ferric Carboxymaltose - FCM); Placebo (Normal Saline)
Intervention description: Intravenous Iron; Normal Saline Solution
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Treatment Phase I and II Primary Objective: To evaluate the efficacy and safety of FCM (750
      mg dose x 2) for treatment of Restless Legs Syndrome (RLS) in patients with iron-deficiency
      anemia (IDA).

      Long-Term Extension Phase III Primary Objective: To evaluate the duration of effect of prior
      FCM treatment and to determine the effectiveness of further iron repletion with FCM when RLS
      symptoms worsen or reoccur.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female subject ≥18 years of age who is able to give informed consent.

          2. Confirmed diagnosis of RLS based on the Cambridge-Hopkins Diagnostic Questionnaire
             (CHDQ) and the Hopkins-Hening Telephone Diagnostic Interview (HDTI).

          3. IRLSS score ≥15 plus RLS symptoms for at least 3 months and currently occurring ≥2
             nights per week.

          4. Iron-deficiency anemia defined as an Hgb <12 g/dl with a ferritin <20 ng/mL, or
             ferritin <100 when TSAT is <18%.

          5. Subjects on sleep medication must be on a stable dose for at least 6 months prior
             screening.

          6. Subjects at risk for pregnancy must have a negative pregnancy test at screening and be
             practicing an acceptable form of birth control, have had a hysterectomy or tubal
             ligation, or otherwise be incapable of pregnancy, or have practiced any of the
             following methods of contraception for at least one month prior to study entry:
             hormonal contraceptives, spermicide with barrier, intrauterine device, or partner
             sterility.

        Exclusion Criteria:

          1. Disorders that require treatment with the same medications used for RLS include:

             peripheral neuropathy and neurodegenerative disorders (i.e. Parkinson's disease or
             dementia).

          2. Current (past 4 weeks) use of drugs that may cause or treat RLS, e.g. opioids, calcium
             channel alpha-2-delta ligands, anti-depressants, dopaminergic agonist or antagonists,
             or centrally-acting antihistamines.

          3. Any medical conditions contraindicated to MRI.

          4. Abnormal MRI at baseline that would confound the outcome measures.

          5. Secondary RLS due to neurological conditions or head trauma.

          6. History of hemochromatosis, hemosiderosis, other iron storage disorders or iron
             metabolism disorders.

          7. Women with clinically significant uterine bleeding (>200 cc blood loss) during the six
             months prior to screening.

          8. Liver transaminases (AST or ALT) greater than two times the upper limit of normal
             (ULN).

          9. Known positive Hepatitis B antigen (HBs Ag), unless positive test can be attributed to
             receipt of Hepatitis B vaccination in childhood or Hepatitis C viral antibody (HCV)
             with evidence of active hepatitis (i.e., AST/ALT greater than two times the ULN).

         10. Known positive HIV-1 or HIV-2 antibodies (anti-HIV).

         11. Active acute or known chronic infections.

         12. Rheumatoid arthritis with symptoms or signs of active inflammation.

         13. Pregnant and lactating women.

         14. Known hypersensitivity reaction to any component of Injectafer® (ferric
             carboxymaltose).

         15. Previously randomized to Injectafer® (FCM or VIT-45) in a clinical trial.

         16. Previous IV iron treatment for RLS.

         17. Parenteral iron, erythropoiesis stimulating agent use or blood transfusion within six
             weeks prior to the screening visit.

         18. Planned elective surgery during the study year.

         19. Chronic alcohol or drug abuse within the past six months.

         20. Any other pre-existing laboratory abnormality, medical condition, or disease that, in
             the opinion of Investigator, may cause the subject to be unsuitable for the study or
             place the subject at potential risk from being in the study, e.g. a malignancy,
             uncontrolled hypertension, unstable ischemic heart disease, or uncontrolled diabetes
             mellitus.

         21. Subject is unwilling or has conditions that would prohibit them from complying with
             the study requirements.