Clinical Trial Results:
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)
Summary
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EudraCT number |
2015-001521-16 |
Trial protocol |
HU CZ PL ES |
Global end of trial date |
02 Jan 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Apr 2021
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First version publication date |
24 Apr 2021
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Other versions |
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Summary report(s) |
2015-001521-16_CSR Synopsis_26Nov2018 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
1VIT14037
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02397057 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Luitpold Pharmaceuticals, Inc.
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Sponsor organisation address |
800 Adams Avenue, Norristown, United States, PA 19403
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Public contact |
Mark Falone, American Regent, mfalone@americanregent.com
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Scientific contact |
Mark Falone, American Regent, mfalone@americanregent.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Oct 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Jan 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Jan 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study is to evaluate the efficacy and safety of an IV Injectafer® in subjects with Restless Leg Syndrome (RLS).
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Protection of trial subjects |
Subjects were informed by the Investigator about the nature of the study, along with the aims, methods, anticipated benefits, potential hazards, and discomfort that participation may have entailed. Written informed consent was obtained from subjects. The study protocol and the informed consent form were submitted to the Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. The study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Nov 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 52
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Country: Number of subjects enrolled |
Spain: 18
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Country: Number of subjects enrolled |
Czechia: 4
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Country: Number of subjects enrolled |
Hungary: 15
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Country: Number of subjects enrolled |
United States: 76
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Country: Number of subjects enrolled |
Ukraine: 44
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Worldwide total number of subjects |
209
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EEA total number of subjects |
89
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
142
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From 65 to 84 years |
66
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85 years and over |
1
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Recruitment
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Recruitment details |
The study was conducted in the US and Europe between 19 February 2015 and 22 January 2017. | ||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
The screening period, starting at Day -7 and following obtainment of informed consent/assent, was of maximum 9 days to allow for all screening results to be obtained and validated. | ||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | ||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Active treatment | ||||||||||||||||||||||||||||||
Arm description |
On Day 0 and Day 5, subjected received 750 mg active investigational medicinal product, Injectafer®, intravenously at 100 mg/mL. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Injectafer®
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Investigational medicinal product code |
Injectafer®
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
750 mg solution for intravenous administration
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Arm title
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Placebo | ||||||||||||||||||||||||||||||
Arm description |
On Day 0 and Day 5, subjects received 15 mL placebo (standard saline solution) IV push. | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
15 ml, IV push
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Baseline characteristics reporting groups
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Reporting group title |
Active treatment
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Reporting group description |
On Day 0 and Day 5, subjected received 750 mg active investigational medicinal product, Injectafer®, intravenously at 100 mg/mL. | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
On Day 0 and Day 5, subjects received 15 mL placebo (standard saline solution) IV push. | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Active treatment
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Reporting group description |
On Day 0 and Day 5, subjected received 750 mg active investigational medicinal product, Injectafer®, intravenously at 100 mg/mL. | ||
Reporting group title |
Placebo
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Reporting group description |
On Day 0 and Day 5, subjects received 15 mL placebo (standard saline solution) IV push. |
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End point title |
IRLS total score | ||||||||||||
End point description |
Change in IRLS total score from baseline to Day 42.
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End point type |
Primary
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End point timeframe |
Baseline
Day 42
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Notes [1] - 2 subjects in placebo group treated with active substances but not analyzed in FAS [2] - 2 subjects in placebo group treated with active substances but not analyzed in FAS |
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Statistical analysis title |
IRLS total score | ||||||||||||
Comparison groups |
Active treatment v Placebo
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Number of subjects included in analysis |
208
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.0043 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Day 0 to Day 365
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
Active treatment
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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13 Jul 2015 |
Amendment (13 July 2015) included the following key changes:
• Day 28 was added to the remote contact by phone procedure.
• Interactive Web Response/Electronic Data Capture was updated to IRT.
• The C-SSRS was added.
• Stratification of subjects by RLS medication-related augmentation was added.
• Definition of intervention was updated.
• RLS therapy prior to screening was revised to specify subjects should be on monotherapy for RLS.
Exclusion criterion #5 (subjects with multiple sclerosis) was added.
• Stratification factor for the CMH test was changed to region (US, EUR).
• Information on the natural history, disease understanding, and treatment guidance for
RLS was updated.
• Length of the study was adjusted from approximately 12½ months to approximately
12 months.
• Procedure for tapering from current RLS medication posttreatment was added.
• An RLS subject diary to record progress was added to the study procedures.
• The following study procedures were added to Day 365 (End of Study):
o Contact IRT to complete subject from study.
o If the subject terminated early or the Day 365 phosphorus value was below the lower limit of normal, the subject should have returned (as directed by the Investigator) for a repeat blood sample until the value was back within normal limits.
• Reporting of SAEs was updated to specify any SAE was to be reported within 24 hours of the Investigator becoming aware of the event.
Time off pre-enrollment prescribed RLS medications was added to the secondary efficacy endpoints |
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02 Jun 2016 |
Amendment (02 June 2016) included the following key changes:
• Further details were added to the RLS tapering treatment regimen:
o Day 6 was added to the timing of tapering from prescribed RLS medication.
o The subject was to be maintained on the lowest dose level attained at the end of the tapering period and that dose was to remain stable for the duration of the subject’s participation in the study.
• A +2-day window was added to the 7-day screening period.
• The time frame for keeping the RLS diary was updated to starting at screening.
• Additional dosing details were revised to specify that central laboratory results obtained during the Day 42 or Day 168 visit could have been used to qualify a subject for additional dosing if those laboratory tests had occurred with 14 days of the first dose of study drug.
• An interim analysis of efficacy was added. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |