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Placebo-Controlled Study to Investigate the Efficacy & Safety of Injectafer in the Treatment of RLS

Primary Purpose

Restless Legs Syndrome (RLS)

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Injectafer
Placebo
Sponsored by
American Regent, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Restless Legs Syndrome (RLS)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Coastal Clinical Research, Inc.
  • Synergy San Diego
  • Desert Valley Research
  • Anderson Clinical Research
  • Neurology Offices of South FL
  • Elite Research Institute
  • MidAmmerica Neuroscience Institute
  • Central Kentucky Research Assoc., Inc.
  • Neuromedical Clinical of Central Louisiana
  • Ctr for Brain & Neuro Care, LLC
  • Massachusetts General Hospital, Sleep Disorders Clinical Research Program
  • Desert Neurology
  • Neurology Center of Las Vegas
  • Guilford Neurologic Associates
  • Metrolina Neurological Associates
  • Saad Upstate Neurology
  • Tri-State Mountain Neurology Associates
  • Egret Bay Neurology
  • The Polyclinic, Madison Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Injectafer

Normal Saline

Arm Description

Two doses of Injectafer 750 mg undiluted dose at 100 mg/minute given 5 days apart for a total of 1500 mgs.

IV Placebo (15ml of Normal Saline) IV push at 2ml/minute

Outcomes

Primary Outcome Measures

International Restless Legs Syndrome (IRLS) Total Score Change From Baseline on Day 42
Summary of the actual values of IRLS total score on baseline and Day 42, and the change from baseline to Day 42. Eligible subjects were to have met the following requirements prior to receiving additional treatment: A baseline score ≥ 15 on the International Restless Legs Syndrome (IRLS) Rating Scale. The minimum score is 15 with the maximum of 40. A score of less than 15 is not an indicator of RLS. However, a score of 15 or greater is an indicator of RLS. Further increase indicates more severe disease.
Proportion of Patients Rated as Much or Very Much Improved With the Clinical Global Impression (CGI) Performed by Investigator (CGI-I)
Responder is defined as subjects rated as much or very much improved with the CGI-I on Day 42. Summary of the number (percentage) of CGI-I responder. Per the protocol, the he CGI is a 3-item observer-rated scale that measures illness severity (CGIS), global improvement or change (CGIC) and therapeutic response. The scale requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention.

Secondary Outcome Measures

Clinical Global Impression-Improvement (CGI-S) by Subject
Similar to the CGI-I except this is self-reported, 7-item scale for assessment of symptoms after treatment with the rating as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Restless Legs Syndrome Quality of Life (RLS-QLI) Change From Baseline to Day 42.
The Restless Legs Syndrome Quality of Life (RLS-QLI) instrument, a self-assessment, 17-item questionnaire with four scales identified through factor analysis: Daily Function, Social Function, Sleep Quality, and Emotional Well-Being, developed to facilitate clinical research on RLS. Scoring Instructions below: Social Function = Sum (Items 1, 2, 3, 4), subtract 4, divide by 16, multiply by 100 Daily Function = Sum (Items 5, 6, 13,14, 15, 16), subtract 6, divide by 24, multiply by 100 Sleep Quality = Sum (Item 7, 8, 9, 17), subtract 4, divide by 18, multiply by 100 Emotional Well-being = Sum (Items 10, 11, 12), subtract 3, divide by 12, multiply by 100 Note: Resulting scores range between 0-100. Higher scores on the RLS-QLI indicate a lower quality of life. Lower scores indicate a higher quality of life.
Fatigue Linear Analog Scale Change From Baseline
The Fatigue Linear Analog Scale is a self-assessment scale in which a 100 mm line is used to measure the severity of fatigue and its effect on a person's activities and lifestyle. The scale severity measure ranges from No Fatigue to Worst Possible Fatigue.
Medical Outcomes Study(MOS) Sleep Scale Change From Baseline to Day 42
The MOS-Sleep scale, is a 12-item standardized, validated questionnaire for assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache which has been demonstrated to be sensitive to RLS treatment effects. This questionnaire provides information about sleep quality. Individual questions can be used for analysis but summary or index scores of a group of questions, is more commonly used in analysis. The "quantity of sleep" dimension is the average number of hours of sleep per night reported by the patient and the "optimal sleep" is a dichotomized version that is "yes" when the number of hours of sleep is 7 or 8. The scores of the dimensions and of the sleep problem index were converted to a 0 to 100 scale, with higher scores reflecting more of the attribute implied by the name (e.g. greater sleep disturbance, greater adequacy of sleep).
Time Off Pre-Enrollment Prescribed Restless Legs Syndrome (RLS) Medications
Subjects could start tapering off pre-enrollment prescribed RLS medications after Day 5 until Day 365.

Full Information

First Posted
March 18, 2015
Last Updated
October 11, 2021
Sponsor
American Regent, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02397057
Brief Title
Placebo-Controlled Study to Investigate the Efficacy & Safety of Injectafer in the Treatment of RLS
Official Title
A Double-Blinded, Multi-Center, Randomized, Placebo-Controlled Study to Investigate the Efficacy and Safety of Injectafer (Ferric Carboxymaltose) in the Treatment of Restless Legs Syndrome (RLS)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
January 2015 (Actual)
Primary Completion Date
January 2018 (Actual)
Study Completion Date
January 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
American Regent, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed Description
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. Subjects will visit the clinic on Days 0 and 5 for treatment, and then on Days 14, 42, 168, and 365. In between the clinic visits subjects will be contacted remotely on Days 84, 126, 210, 252, 294, and 336. The subject's participation in the study will be for approximately 1 year from Day 0.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Restless Legs Syndrome (RLS)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
209 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Injectafer
Arm Type
Active Comparator
Arm Description
Two doses of Injectafer 750 mg undiluted dose at 100 mg/minute given 5 days apart for a total of 1500 mgs.
Arm Title
Normal Saline
Arm Type
Placebo Comparator
Arm Description
IV Placebo (15ml of Normal Saline) IV push at 2ml/minute
Intervention Type
Drug
Intervention Name(s)
Injectafer
Other Intervention Name(s)
Ferinject®, Iroprem®, Renegy®
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normal Saline
Primary Outcome Measure Information:
Title
International Restless Legs Syndrome (IRLS) Total Score Change From Baseline on Day 42
Description
Summary of the actual values of IRLS total score on baseline and Day 42, and the change from baseline to Day 42. Eligible subjects were to have met the following requirements prior to receiving additional treatment: A baseline score ≥ 15 on the International Restless Legs Syndrome (IRLS) Rating Scale. The minimum score is 15 with the maximum of 40. A score of less than 15 is not an indicator of RLS. However, a score of 15 or greater is an indicator of RLS. Further increase indicates more severe disease.
Time Frame
Baseline and Day 42
Title
Proportion of Patients Rated as Much or Very Much Improved With the Clinical Global Impression (CGI) Performed by Investigator (CGI-I)
Description
Responder is defined as subjects rated as much or very much improved with the CGI-I on Day 42. Summary of the number (percentage) of CGI-I responder. Per the protocol, the he CGI is a 3-item observer-rated scale that measures illness severity (CGIS), global improvement or change (CGIC) and therapeutic response. The scale requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention.
Time Frame
Day 42
Secondary Outcome Measure Information:
Title
Clinical Global Impression-Improvement (CGI-S) by Subject
Description
Similar to the CGI-I except this is self-reported, 7-item scale for assessment of symptoms after treatment with the rating as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Time Frame
Day 42
Title
Restless Legs Syndrome Quality of Life (RLS-QLI) Change From Baseline to Day 42.
Description
The Restless Legs Syndrome Quality of Life (RLS-QLI) instrument, a self-assessment, 17-item questionnaire with four scales identified through factor analysis: Daily Function, Social Function, Sleep Quality, and Emotional Well-Being, developed to facilitate clinical research on RLS. Scoring Instructions below: Social Function = Sum (Items 1, 2, 3, 4), subtract 4, divide by 16, multiply by 100 Daily Function = Sum (Items 5, 6, 13,14, 15, 16), subtract 6, divide by 24, multiply by 100 Sleep Quality = Sum (Item 7, 8, 9, 17), subtract 4, divide by 18, multiply by 100 Emotional Well-being = Sum (Items 10, 11, 12), subtract 3, divide by 12, multiply by 100 Note: Resulting scores range between 0-100. Higher scores on the RLS-QLI indicate a lower quality of life. Lower scores indicate a higher quality of life.
Time Frame
Baseline and Day 42
Title
Fatigue Linear Analog Scale Change From Baseline
Description
The Fatigue Linear Analog Scale is a self-assessment scale in which a 100 mm line is used to measure the severity of fatigue and its effect on a person's activities and lifestyle. The scale severity measure ranges from No Fatigue to Worst Possible Fatigue.
Time Frame
Baseline and Day 42
Title
Medical Outcomes Study(MOS) Sleep Scale Change From Baseline to Day 42
Description
The MOS-Sleep scale, is a 12-item standardized, validated questionnaire for assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache which has been demonstrated to be sensitive to RLS treatment effects. This questionnaire provides information about sleep quality. Individual questions can be used for analysis but summary or index scores of a group of questions, is more commonly used in analysis. The "quantity of sleep" dimension is the average number of hours of sleep per night reported by the patient and the "optimal sleep" is a dichotomized version that is "yes" when the number of hours of sleep is 7 or 8. The scores of the dimensions and of the sleep problem index were converted to a 0 to 100 scale, with higher scores reflecting more of the attribute implied by the name (e.g. greater sleep disturbance, greater adequacy of sleep).
Time Frame
Change from Baseline and Day 42.
Title
Time Off Pre-Enrollment Prescribed Restless Legs Syndrome (RLS) Medications
Description
Subjects could start tapering off pre-enrollment prescribed RLS medications after Day 5 until Day 365.
Time Frame
Time from Day 5 to Day 365

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subject's ≥18 years of age, willing and able to give informed consent to the study. RLS symptoms affirming diagnosis. The IRLS Diagnostic Criteria must be met: 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. The urge to move or unpleasant sensations are worse or exclusively present at rest or inactivity, such as lying down or sitting. The urge to move or unpleasant sensations are partially/temporarily relieved with walking or moving the legs. 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. 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). A score ≥15 on the IRLS Rating Scale at screening and on Day 0 prior to dosing. Subjects on anti-depressants and sleep medications must be on a stable dose for at least 6 months. Subject has regular sleep hours between 9 pm and 9 am. 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: RLS 2° to other disease or injury. Disorders that require treatment with the same medications used for RLS include: peripheral neuropathy and neurodegenerative disorders (i.e. Parkinson's Disease or Dementia). Stage 4 - 5 CKD, subjects on dialysis or anticipated to start dialysis while participating in this study. 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. Subjects with multiple sclerosis. History of neuroleptic akathisia. Parenteral iron use within 6 weeks prior to screening. History of >10 blood transfusions in the past 2 years. Anticipated need for blood transfusion during the study. Known hypersensitivity reaction to any component of Injectafer® (Ferric Carboxymaltose). Previously randomized to Injectafer® (FCM or VIT-45) in a clinical trial. Current, active or acute or chronic infection other than viral upper respiratory tract infection Malignancy (other than basal or squamous cell skin cancer or the subject has been cancer free for ≥ 5 years). Pregnant or lactating women. Seizure disorder currently being treated with medication. Baseline ferritin ≥300 ng/mL. Baseline TSAT ≥45%. History of hemochromatosis, hemosiderosis, or other iron storage disorders. AST or ALT greater than 2 times the upper limit of normal (ULN). Hemoglobin greater than the ULN. 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). Known positive HIV-1/HIV-2 antibodies (anti-HIV). Received an investigational drug within 30 days before randomization. Chronic alcohol or drug abuse within the past 6 months. 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. Subject unable or unwilling to comply with the study requirements.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Falone, MD
Organizational Affiliation
American Regent, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Coastal Clinical Research, Inc.
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
Facility Name
Synergy San Diego
City
National City
State/Province
California
ZIP/Postal Code
91950
Country
United States
Facility Name
Desert Valley Research
City
Rancho Mirage
State/Province
California
ZIP/Postal Code
92270
Country
United States
Facility Name
Anderson Clinical Research
City
Redlands
State/Province
California
ZIP/Postal Code
92374
Country
United States
Facility Name
Neurology Offices of South FL
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33428
Country
United States
Facility Name
Elite Research Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33169
Country
United States
Facility Name
MidAmmerica Neuroscience Institute
City
Lenexa
State/Province
Kansas
ZIP/Postal Code
66214-1505
Country
United States
Facility Name
Central Kentucky Research Assoc., Inc.
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40509
Country
United States
Facility Name
Neuromedical Clinical of Central Louisiana
City
Alexandria
State/Province
Louisiana
ZIP/Postal Code
71301
Country
United States
Facility Name
Ctr for Brain & Neuro Care, LLC
City
Fulton
State/Province
Maryland
ZIP/Postal Code
20759
Country
United States
Facility Name
Massachusetts General Hospital, Sleep Disorders Clinical Research Program
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Desert Neurology
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89119
Country
United States
Facility Name
Neurology Center of Las Vegas
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Facility Name
Guilford Neurologic Associates
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27405
Country
United States
Facility Name
Metrolina Neurological Associates
City
Indian Land
State/Province
South Carolina
ZIP/Postal Code
29707
Country
United States
Facility Name
Saad Upstate Neurology
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29307
Country
United States
Facility Name
Tri-State Mountain Neurology Associates
City
Johnson City
State/Province
Tennessee
ZIP/Postal Code
37604
Country
United States
Facility Name
Egret Bay Neurology
City
Houston
State/Province
Texas
ZIP/Postal Code
77058
Country
United States
Facility Name
The Polyclinic, Madison Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States

12. IPD Sharing Statement

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Placebo-Controlled Study to Investigate the Efficacy & Safety of Injectafer in the Treatment of RLS

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