COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Randomized, Placebo-controlled Trial of Ferric Carboxymaltose in RLS Patients With Iron-deficiency Anemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02826681
Recruitment Status : Recruiting
First Posted : July 11, 2016
Last Update Posted : January 27, 2020
Information provided by (Responsible Party):
American Regent, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Restless Legs Syndrome (RLS) Drug: Injectafer® (Ferric Carboxymaltose - FCM) Drug: Placebo (Normal Saline) Phase 2

Detailed Description:

This will be a Phase II, randomized, placebo-controlled study. All subjects who meet the inclusion criteria, with no exclusion criteria, will qualify to enter the Screening Phase. The study will enroll 70 eligible subjects to receive blinded study drug in Treatment Phase I. All eligible subjects will be randomized in a 1:1 ratio to receive a blinded dose of either FCM 750 mg undiluted slow intravenous (IV) push at 100 mg/minute or a Placebo (15 ml of Normal Saline [NS]) IV push at 2 ml/minute on Day 0 and 7.

A subject will be defined at Day 42 as a Responder if the International Restless Legs Syndrome Severity Scale (IRLSS) score is ≤10 or if the IRLSS score is >10 with a Clinical Global Impression-Improvement (CGI-I) score of much or very much improvement and the subject does not request further treatment for RLS. A subject will be defined as a treatment Non-Responder if neither of these criteria are met.

Non-Responders who do not meet the laboratory criteria for additional dosing will be discontinued from the study and treated for RLS as deemed appropriate by the referring physician. Subjects who are Non-Responders at the end of Treatment Phase I and met the necessary laboratory criteria (ferritin <300 ng/mL and a TSAT <45%) will consented for enrollment in Treatment Phase II of the study. These subjects will receive the first of two unblinded doses of FCM (undiluted slow IV push 750 mg 100 mg/minute) on Day 0 of Phase II, which will occur within 7 days of the completing Treatment Phase I visit. The subjects will then receive the second dose of FCM (undiluted slow IV push 750 mg 100 mg/minute) on Day 7. All treated subjects will have blood samples taken for hematology, chemistries and iron indices on Day 14. Treatment efficacy (IRLSS score), medication review and adverse events assessment by phone will be done on Day 28. All subjects will return to the clinic on Day 42 for end of study assessments. Subjects completing Treatment Phase II will be re-evaluated on Day 42 and defined as either a Responder or Non-Responder, using the same criteria described above. Subjects deemed as treatment Non-Responders will be discontinued from the study after final assessments are complete.

Subjects who are evaluated on Day 42 (Week 6) as Responders from either Treatment Phase I or Treatment Phase II will continue through into the 46-Week, Long-Term Extension Phase III of the study, and be monitored and assessed by phone for RLS symptoms (IRLSS and Hopkins RLS-Sleep Quality Questionnaire [HRSQ]) and adverse events on (approximately every 9 weeks) Weeks 15, 25, 34, 43 and 52 (final follow-up visit). During Phase III subjects may receive additional unblinded treatments with FCM if at any time the subject reports worsening of RLS symptoms (an increase >4 points on the IRLSS compared to the last evaluation captured for that subject) and laboratory criteria are met (ferritin <300 ng/mL and a TSAT <45%). Subjects will receive a single FCM 750 mg undiluted slow IV push at 100 mg/minute. See section 6.6 for dosing and assessment outline. No additional treatment will be allowed after the Week 46. A final face-to-face study visit will occur on Week 52 (approximately 365 days since initial Day 0 Treatment). If a clinic visit is not possible, final evaluation will be completed by phone.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Placebo-controlled Trial of Ferric Carboxymaltose in Restless Legs Syndrome Patients With Iron-deficiency Anemia
Actual Study Start Date : May 24, 2017
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Injectafer
750 mg undiluted slow IVpush (100 mg/minute) of Injectafer® (Ferric Carboxymaltose - FCM)
Drug: Injectafer® (Ferric Carboxymaltose - FCM)
Intravenous Iron
Other Names:
  • Ferinject®
  • Iroprem®
  • Renegy®

Placebo Comparator: Normal Saline
Placebo (15 ml of Normal Saline [NS]) IV push at 2 ml/minute on Day 0 and 7.
Drug: Placebo (Normal Saline)
Normal Saline Solution
Other Name: Normal Saline

Primary Outcome Measures :
  1. Treatment Phase I: IRLSS score change [ Time Frame: Baseline to Day 42 ]
    IRLSS (International Restless Legs Syndrome Severity Scale) score change from baseline to Day 42 with comparison between FCM (Ferric Carboxymaltose) vs. Placebo.

  2. Treatment Phase I: CGI-I [ Time Frame: Day 42 ]
    CGI-I (Clinical Global Impression- Improvement) at Day 42.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02826681

Layout table for location contacts
Contact: James Bambrick, BS 631-772-3518
Contact: Mark Falone, MD 610-650-4200

Layout table for location information
United States, California
Synergy San Diego Active, not recruiting
Lemon Grove, California, United States, 91945
United States, Florida
Alliance for Multispeciality Research Active, not recruiting
Fort Myers, Florida, United States, 33912
United States, Maryland
Johns Hopkins Bayview Medical Center Recruiting
Baltimore, Maryland, United States, 21224-2780
Contact: Emily Rost    410-550-1046   
Principal Investigator: Christopher Earley, MD         
United States, Massachusetts
Boston Neuro Research Recruiting
South Dartmouth, Massachusetts, United States, 02169
Contact: Nicole Pires    281-783-4159   
Principal Investigator: Mushtaque Chachar, MD         
United States, Nevada
Neurology Center of Las Vegas Recruiting
Las Vegas, Nevada, United States, 89128
Contact: Angela Gomez    702-425-1798   
Principal Investigator: Shanker Dixit, MD         
United States, Texas
Clinical Trial Network Active, not recruiting
Houston, Texas, United States, 77074
United States, Washington
The Polyclinic Active, not recruiting
Seattle, Washington, United States, 98104
Sponsors and Collaborators
American Regent, Inc.
Layout table for additonal information
Responsible Party: American Regent, Inc. Identifier: NCT02826681    
Other Study ID Numbers: 1VIT15042
First Posted: July 11, 2016    Key Record Dates
Last Update Posted: January 27, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Psychomotor Agitation
Restless Legs Syndrome
Anemia, Iron-Deficiency
Pathologic Processes
Hematologic Diseases
Anemia, Hypochromic
Iron Metabolism Disorders
Metabolic Diseases
Neurologic Manifestations
Nervous System Diseases
Psychomotor Disorders
Neurobehavioral Manifestations
Signs and Symptoms
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Mental Disorders