Clinical Trial Results:
An open label study on safety and pharmacokinetics of an intravenous administered single dose of Feramyl 200 mg in healthy blood donors compared to a single dose of Feramyl 1000 mg in IBD patients to evaluate dose dependency and kinetics after 1 hour infusion.
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Summary
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EudraCT number |
2013-001123-39 |
Trial protocol |
DK |
Global end of trial date |
29 Sep 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
15 May 2016
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First version publication date |
15 May 2016
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Other versions |
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Summary report(s) |
Synopsis SWB0113 |
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 |
SWB0113
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Serumwerk Bernburg AG
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Sponsor organisation address |
Hallesche Landstrasse 105b, Bernburg, Germany, 06406
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Public contact |
Susanne Manhart, Serumwerk Bernburg, +49 3471860180, smanhart@serumwerk.de
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Scientific contact |
Susanne Manhart, Serumwerk Bernburg, +49 3471860180, smanhart@serumwerk.de
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Sponsor organisation name |
Serumwerk Bernburg AG
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Sponsor organisation address |
hallesche Landstrasse 105 b, Bernburg, Germany, 06406
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Public contact |
Susanne Manhart, Serumwerk Bernburg AG, 0049 03471860180, smanhart@serumwerk.de
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Scientific contact |
Susanne Manhart, Serumwerk Bernburg AG, 0049 03471860180, smanhart@serumwerk.de
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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 |
29 Sep 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Sep 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Sep 2013
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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 |
To evaluate the dose dependency of Feramyl 200 mg vs. Feramyl 1000 mg administered over 1 hour intravenously with respect to Cmax, Tmax and AUC,
To evaluate the safety of 1-hour infusion time by monitoring of vital signs and clinical chemical safety parameters,
To evaluate the Cmax, Tmax, AUC, half-life, elimination constant, volumes of distribution and urine excretion compared to literature data for competitors and
To evaluate standard clinical chemistry safety parameters and compare the results after 200 mg to 1000 mg and compare literature data for competitors
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Protection of trial subjects |
The protocol was approved by local ethics committee and competent authority. The trial was conducted in accordance with good clinical practice and the Declaration of Helsinki. Informed consent was obtained in writing prior to any trial-related activities.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Jun 2013
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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 |
Denmark: 15
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Worldwide total number of subjects |
15
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EEA total number of subjects |
15
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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) |
15
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were screened in the period June 2013 to September 2013. The trial took place at one site in Denmark. | ||||||||||||
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Pre-assignment
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Screening details |
Healthy blood donors, who have donated at least 400 ml blood within the last 2 weeks. Age between 18–45 years and who were willing to provide written informed consent were considered eligible to participate in the trial. | ||||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Healthy blood donors | ||||||||||||
Arm description |
Healthy blood donors, who had donated at least 400 ml within the last two weeks, Feramyl 200 mg diluted in 100 ml 0.9% NaCL solution, administered intravenously in 60 minutes | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Feramyl
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Investigational medicinal product code |
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Other name |
iron HES
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
single dose, intraveneous infusion over 60 min
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Baseline characteristics reporting groups
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Reporting group title |
Healthy blood donors
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Reporting group description |
Healthy blood donors, who had donated at least 400 ml within the last two weeks, Feramyl 200 mg diluted in 100 ml 0.9% NaCL solution, administered intravenously in 60 minutes | ||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
PK/Efficacy
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Fourteen subjects were dosed and were available for the safety analysis. Samples from six patients were not analyzed for pharmacokinetic analysis since their blood samples were accidentally destroyed. Hence eight subjects completed the study and were available for pharmacokinetic analysis
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Subject analysis set title |
Safety
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Fourteen subjects were dosed and were available for the safety analysis.
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End points reporting groups
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Reporting group title |
Healthy blood donors
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Reporting group description |
Healthy blood donors, who had donated at least 400 ml within the last two weeks, Feramyl 200 mg diluted in 100 ml 0.9% NaCL solution, administered intravenously in 60 minutes | ||
Subject analysis set title |
PK/Efficacy
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Fourteen subjects were dosed and were available for the safety analysis. Samples from six patients were not analyzed for pharmacokinetic analysis since their blood samples were accidentally destroyed. Hence eight subjects completed the study and were available for pharmacokinetic analysis
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Subject analysis set title |
Safety
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Fourteen subjects were dosed and were available for the safety analysis.
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End point title |
dose-dependency cmax, tmax, AUC [1] | ||||||||
End point description |
The primary efficacy endpoint was to evaluate the dose dependency of Feramyl 200 mg vs. Feramyl 1000 mg administered over 1 hour intravenously with respect to Cmax, Tmax and AUC. The primary efficacy endpoint could not be addressed because no subject was dosed with Feramyl 1000 mg. This in turn was because none of the IBD anaemia patients were recruited in the group as it proved difficult due to the inclusion and the exclusion criteria.
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End point type |
Primary
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End point timeframe |
Enrollment period: Visit 1 (-1 week)
Treatment period: Visit 2 (Day 1), Visit 3 (Day 2), Visit 4 (Day 7)
Blood sampling time Points (h): -0.25, 0.01, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 24.00, 168.00
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary efficacy endpoint was to evaluate the dose dependency of Feramyl 200 mg vs. Feramyl 1000 mg administered over 1 hour intravenously with respect to Cmax, Tmax and AUC. The primary efficacy endpoint could not be addressed because no subject was dosed with Feramyl 1000 mg. This in turn was because none of the IBD anaemia patients were recruited in the group as it proved difficult due to the inclusion and the exclusion criteria. |
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| Notes [2] - The primary efficacy endpoint could not be addressed because no subject was dosed with Feramyl 1000 |
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| No statistical analyses for this end point | |||||||||
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End point title |
safety of a1-hour infusion [3] | ||||||||||
End point description |
The primary safety endpoint was to evaluate the safety of a1-hour infusion time by monitoring vital signs, clinical chemical safety parameters and adverse events.
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End point type |
Primary
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End point timeframe |
Enrollment period: Visit 1 (-1 week)
Treatment period: Visit 2 (Day 1), Visit 3 (Day 2), Visit 4 (Day 7)
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: for incidence of AEs and SAEs no statistical analysis was done also because of small number of cases |
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| Notes [4] - 5 adverse events in 3 subjects, all mild in nature and unlikely related to study drug |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Cmax | ||||||||||
End point description |
The secondary efficacy endpoints were to evaluate the Cmax, Tmax, AUC, half life, elimination constants, volumes of distribution and urine excretion compared to literature data for competitors.Cmax, the maximum observed serum concentration. Non-compartmental PK Analysis. The coefficient of determination, R2, for λz has to be >0.85 otherwise estimates of AUC, t½, Vz, and CL are not acceptable. AUC%Extrap should preferably not exceed 25 % in order not to reduce precision of AUC, Vz and CL.
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End point type |
Secondary
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End point timeframe |
Enrollment period: Visit 1 (-1 week)
Treatment period: Visit 2 (Day 1), Visit 3 (Day 2), Visit 4 (Day 7)
Blood sampling time Points (h): -0.25, 0.01, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 24.00, 168.00
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| No statistical analyses for this end point | |||||||||||
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End point title |
tmax | ||||||||||
End point description |
The secondary efficacy endpoints were to evaluate the Cmax, Tmax, AUC, half life, elimination constants, volumes of distribution and urine excretion compared to literature data for competitors.
tmax, time for occurrence of Cmax. Non-compartmental PK analysis. The coefficient of determination, R2, for λz has to be >0.85 otherwise estimates of AUC, t½, Vz, and CL are not acceptable. AUC%Extrap should preferably not exceed 25 % in order not to reduce precision of AUC, Vz and CL.
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End point type |
Secondary
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End point timeframe |
Enrollment period: Visit 1 (-1 week)
Treatment period: Visit 2 (Day 1), Visit 3 (Day 2), Visit 4 (Day 7)
Blood sampling time Points (h): -0.25, 0.01, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 24.00, 168.00
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| No statistical analyses for this end point | |||||||||||
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End point title |
AUC (0-t) | ||||||||||
End point description |
The secondary efficacy endpoints were to evaluate the Cmax, Tmax, AUC, half life, elimination constants, volumes of distribution and urine excretion compared to literature data for competitors.
AUC(0-t), the area under the serum concentration curve from zero until the last concentration, Cz, calculated from the linear trapezoidal rule. Non-compartmental PK analysis. The coefficient of determination, R2, for λz has to be >0.85 otherwise estimates of AUC, t½, Vz, and CL are not acceptable. AUC%Extrap should preferably not exceed 25 % in order not to reduce precision of AUC, Vz and CL.
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End point type |
Secondary
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End point timeframe |
Enrollment period: Visit 1 (-1 week)
Treatment period: Visit 2 (Day 1), Visit 3 (Day 2), Visit 4 (Day 7)
Blood sampling time Points (h): -0.25, 0.01, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 24.00, 168.00
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| No statistical analyses for this end point | |||||||||||
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End point title |
Lambda z | ||||||||||
End point description |
The secondary efficacy endpoints were to evaluate the Cmax, Tmax, AUC, half-life, elimination constants, volumes of distribution and urine excretion compared to literature data for competitors.
λz, the terminal slope of the serum concentration curve in a semi-logarithmic plot used for calculation of t½, the terminal half-life. Non-compartmental PK analysis. The coefficient of determination, R2, for λz has to be >0.85 otherwise estimates of AUC, t½, Vz, and CL are not acceptable. AUC%Extrap should preferably not exceed 25 % in order not to reduce precision of AUC, Vz and CL.
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End point type |
Secondary
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End point timeframe |
Enrollment period: Visit 1 (-1 week)
Treatment period: Visit 2 (Day 1), Visit 3 (Day 2), Visit 4 (Day 7)
Blood sampling time Points (h): -0.25, 0.01, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 24.00, 168.00
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| No statistical analyses for this end point | |||||||||||
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End point title |
half-life | ||||||||||
End point description |
The secondary efficacy endpoints were to evaluate the Cmax, Tmax, AUC, half life, elimination constants, volumes of distribution and urine excretion compared to literature data for competitors.
t½, the terminal half-life. Non-compartmental PK analysis. The coefficient of determination, R2, for λz has to be >0.85 otherwise estimates of AUC, t½, Vz, and CL are not acceptable. AUC%Extrap should preferably not exceed 25 % in order not to reduce precision of AUC, Vz and CL.
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End point type |
Secondary
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End point timeframe |
Enrollment period: Visit 1 (-1 week)
Treatment period: Visit 2 (Day 1), Visit 3 (Day 2), Visit 4 (Day 7)
Blood sampling time Points (h): -0.25, 0.01, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 24.00, 168.00
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| No statistical analyses for this end point | |||||||||||
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End point title |
volume of distribution | ||||||||||
End point description |
The secondary efficacy endpoints were to evaluate the Cmax, Tmax, AUC, half life, elimination constants, volumes of distribution and urine excretion compared to literature data for competitors.
Vz,the apparent volume of distribution during the terminal phase. Non-compartmental PK analysis. The coefficient of determination, R2, for λz has to be >0.85 otherwise estimates of AUC, t½, Vz, and CL are not acceptable. AUC%Extrap should preferably not exceed 25 % in order not to reduce precision of AUC, Vz and CL.
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End point type |
Secondary
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End point timeframe |
Enrollment period: Visit 1 (-1 week)
Treatment period: Visit 2 (Day 1), Visit 3 (Day 2), Visit 4 (Day 7)
Blood sampling time Points (h): -0.25, 0.01, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 24.00, 168.00
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| No statistical analyses for this end point | |||||||||||
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End point title |
iron urine exretion | ||||||||||
End point description |
The secondary efficacy endpoints were to evaluate the Cmax, Tmax, AUC, half life, elimination constants, volumes of distribution and urine excretion compared to literature data for competitors.
Fe in Urine was below Limit of qualification in all subjects.
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End point type |
Secondary
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End point timeframe |
Enrollment period: Visit 1 (-1 week)
Treatment period: Visit 2 (Day 1), Visit 3 (Day 2), Visit 4 (Day 7)
Urine sampling period: -2 - 0 hours pre-dose, 0 - 8 hours post-dose, 8 - 24 hours post-dose
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| Notes [5] - Fe in urine was below limit of quantification |
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| No statistical analyses for this end point | |||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the time a subject had signed the ICF and until he/she has completed the study, all AEs/SAEs were collected in the CRF.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
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Reporting groups
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Reporting group title |
Healthy blood donors
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Reporting group description |
Healthy blood donors received 200 mg Feramyl diluted in 100 ml Saline solution as intravenous Infusion within 1 hour. | ||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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. | |||
| The primary efficacy endpoint could not be addressed because no subject was dosed with Feramyl 1000 mg. This in turn was because none of the IBD anaemia patients were recruited in the group as it proved difficult due to the inclusion and the exclusio | |||
