Placebo-Controlled Study to Investigate the Efficacy & Safety of Injectafer in the Treatment of RLS
Condition: Restless Legs Syndrome (RLS)
MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome
Intervention: Injectafer; Placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 209.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This will be a Phase III, double blinded, multi-center, randomized, placebo-controlled study.
      Eligible subjects will be randomized in a 1:1 ratio to receive Injectafer or Placebo on days
      0 and 5. All treated subjects will be followed for efficacy and safety for 12 months. The
      subject's participation in the study will be for approximately 1 year from Day 0.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female subject's ≥18 years of age, willing and able to give informed consent
             to the study.

          2. RLS symptoms affirming diagnosis. The IRLS Diagnostic Criteria must be met:

               1. An urge (distressing need) to move the legs usually associated with painful or
                  uncomfortable sensations in the legs. The urge to move may be present without the
                  uncomfortable sensations. The arms or other body parts may be involved in
                  addition to the legs.

               2. The urge to move or unpleasant sensations are worse or exclusively present at
                  rest or inactivity, such as lying down or sitting.

               3. The urge to move or unpleasant sensations are partially/temporarily relieved with
                  walking or moving the legs.

               4. The urge to move or unpleasant sensations are worse in the evening or night than
                  during the day or only occur in the evening or night. When symptoms are severe,
                  the worsening at night may not be noticeable but must have been previously
                  present.

          3. Subjects should be on monotherapy for RLS. Treatment should be stable for at least 8
             weeks prior to screening (See approved RLS Therapies/Regimen in Appendix III).

          4. A score ≥15 on the IRLS Rating Scale at screening and on Day 0 prior to dosing.

          5. Subjects on anti-depressants and sleep medications must be on a stable dose for at
             least 6 months.

          6. Subject has regular sleep hours between 9 pm and 9 am.

          7. Subjects at risk for pregnancy must have a negative pregnancy test at baseline 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. RLS 2° to other disease or injury.

          2. Disorders that require treatment with the same medications used for RLS include:
             peripheral neuropathy and neurodegenerative disorders (i.e. Parkinson's Disease or
             Dementia).

          3. Stage 4 - 5 CKD, subjects on dialysis or anticipated to start dialysis while
             participating in this study.

          4. Any pain related (e.g., frequent muscle cramps, myalgia, fibromyalgia) or sleep
             related disorders (e.g. sleep apnea, unless on stable Continuous Positive Airway
             Pressure [CPAP]) which may confound the outcome measures.

          5. Subjects with multiple sclerosis.

          6. History of neuroleptic akathisia.

          7. Parenteral iron use within 6 weeks prior to screening.

          8. History of >10 blood transfusions in the past 2 years.

          9. Anticipated need for blood transfusion during the study.

         10. Known hypersensitivity reaction to any component of Injectafer® (Ferric
             Carboxymaltose).

         11. Previously randomized to Injectafer® (FCM or VIT-45) in a clinical trial.

         12. Current, active or acute or chronic infection other than viral upper respiratory tract
             infection

         13. Malignancy (other than basal or squamous cell skin cancer or the subject has been
             cancer free for ≥ 5 years).

         14. Pregnant or lactating women.

         15. Seizure disorder currently being treated with medication.

         16. Baseline ferritin ≥300 ng/mL.

         17. Baseline TSAT ≥45%.

         18. History of hemochromatosis, hemosiderosis, or other iron storage disorders.

         19. AST or ALT greater than 2 times the upper limit of normal (ULN).

         20. Hemoglobin greater than the ULN.

         21. Known positive hepatitis B antigen (HBsAg), 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 the upper limit of
             normal).

         22. Known positive HIV-1/HIV-2 antibodies (anti-HIV).

         23. Received an investigational drug within 30 days before randomization.

         24. Chronic alcohol or drug abuse within the past 6 months.

         25. Any other pre-existing laboratory abnormality, medical condition or disease, which per
             the investigator may put the subject at risk if they participate in the study.

         26. Subject unable or unwilling to comply with the study requirements.