Download PDF

Clinical Trial Results:
A Phase IV, multi-centre, randomized, open label study to investigate the efficacy and safety of Floradix® mit Eisen and ferro sanol® duodenal mite 50 mg in pregnant women with diagnosed iron deficiency

Summary
EudraCT number	2010-018940-15
Trial protocol	DE
Global end of trial date	28 Nov 2013

Results information
Results version number	v1(current)
This version publication date	13 Aug 2022
First version publication date	13 Aug 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

FLDX-001

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

SALUS Haus GmbH & Co. KG

Sponsor organisation address

Bahnhofstraße 24, Bruckmühl, Germany, 83052

Public contact

Dr. med. vet. Jana D'Alascio, Medical Consulting Dr. Schlichtinger GmbH Nußbaumstraße 10 80336 München Germany, 0049 89 673 7916,

Scientific contact

Dr. med. Claus A.Hanusch, Rotkreuzklinikum München - Frauenklinik Taxisstraße 3 80637 München Germany, 0049 89 157 06 620,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

05 Dec 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Nov 2013

Was the trial ended prematurely?

Main objective of the trial

To gather information on the efficacy and safety profile of a long-term treatment with Floradix® mit Eisen and to compare descriptively against a treatment with ferro sanol® duodenal mite 50mg

Protection of trial subjects

none

Background therapy

Evidence for comparator

Actual start date of recruitment

11 Oct 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 26

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

4 sites should recruit a total of 40 randomized patients, i.e.female caucasians with mean gestation duration of 26 weeks. Early termination of recruitment: A nearly 50% screening failure rate resulted in the fact that after 3 and a half year field phase only 26 patients could be randomised. The sponsor then decided to terminate recruitment.

Screening details

Age (years): 32.8 +/- 5.6 Height (cm): 165.0 +/- 6.3 Weight (kg): 66.5 +/- 11.3 BMI (kg/m2): 24.4 +/- 3.9

Number of subjects started

49 ^[1]

Number of subjects completed

Reason: Number of subjects

Screening Failures: 23

Notes
[1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 49 patients were screened, 26 of them were randomized.

Period 1 title

Randomization visit

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Floradix mit Eisen (baseline)

Arm description

Arm type

Experimental

Investigational medicinal product name

Floradix mit Eisen

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Oral use

Dosage and administration details

Oral intake of solution Floradix mit Eisen: 3 x 15 ml per day

Ferro sanol duodenal mite 50 mg (baseline)

Arm description

Arm type

Experimental

Investigational medicinal product name

ferro sanol duodenal mite 50 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Oral intake of capsule 1 capsule per day

Number of subjects in period 1	Floradix mit Eisen (baseline)	Ferro sanol duodenal mite 50 mg (baseline)
Started	13	13
Completed	13	13

Period 2 title

Treatment period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Floradix mit Eisen

Arm description

Arm type

Experimental

Investigational medicinal product name

Floradix mit Eisen

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Oral use

Dosage and administration details

Oral intake of solution Floradix mit Eisen: 3 x 15 ml per day

Ferro sanol duodenal mite 50 mg

Arm description

Arm type

multicentre, open label

Investigational medicinal product name

Ferro sanol duodenal mite 50 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Oral intake of capsule 1 capsule per day

Number of subjects in period 2	Floradix mit Eisen	Ferro sanol duodenal mite 50 mg
Started	13	13
Completed	11	11
Not completed	2	2
change of physician	1	-
Adverse event, non-fatal	1	-
Lack of efficacy	-	1
lack of compliance	-	1

Baseline characteristics

Top of page

Reporting group title

Floradix mit Eisen (baseline)

Reporting group description

Reporting group title

Ferro sanol duodenal mite 50 mg (baseline)

Reporting group description

Reporting group values	Floradix mit Eisen (baseline)	Ferro sanol duodenal mite 50 mg (baseline)	Total
Number of subjects	13	13	26
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	13	13	26
From 65-84 years	0	0	0
85 years and over	0	0	0
Gender categorical
Units: Subjects
Female	13	13	26
Male	0	0	0

End points

Top of page

Reporting group title

Floradix mit Eisen (baseline)

Reporting group description

Reporting group title

Ferro sanol duodenal mite 50 mg (baseline)

Reporting group description

Reporting group title

Floradix mit Eisen

Reporting group description

Reporting group title

Ferro sanol duodenal mite 50 mg

Reporting group description

Subject analysis set title

Full Analysis Set

Subject analysis set type

Full analysis

Subject analysis set description

The Full Analysis Set included all enrolled patients who received at least 1 dose of study drug and had at least 1 valid post-baseline Hb measurement.

Subject analysis set title

Safety Set

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Set included all enrolled patients who received at least 1 dose of study drug.

Primary: Baseline change of haemoglobin (Hb) measurements (w12 - w0)

Top of page

End point title

Baseline change of haemoglobin (Hb) measurements (w12 - w0)

End point description

Values displayed here are the ones from study week12 compared to baseline w0. For Hb changes (vs. baseline) calculated for previous visits, please refer to attached document. For Hb values recorded for w14 and after birth, please also refer to attacher overview. Changes of Hb w14-w0 were not calculated due to low number of patients in each arm. Changes of Hb after birth-w0 were not calculated due to missing values for w14-w0.

End point type

Primary

End point timeframe

Hb measurements were done prior to randomisation (visit 1, visit 2 (= baseline, i.e. week 0) and after 4, 6, 8, 10, 12, 14 weeks and at a last measurement 6 -8 weeks after birth.

End point values	Floradix mit Eisen	Floradix mit Eisen (baseline)	Ferro sanol duodenal mite 50 mg (baseline)	Ferro sanol duodenal mite 50 mg
Number of subjects analysed	11	12	12	9
Units: Haemoglobin (g/dl)
arithmetic mean (standard deviation)	1.72 ± 1.35	0 ± 0	0 ± 0	1.27 ± 0.84

Attachments

Untitled (Filename: CSR_SALUS_FINAL_1.0_05Dec2014_Section 11 EFFICACY RESULTS.pdf)

Baseline difference w12-w0, Floradix mit Eisen

Statistical analysis description

Changes of Hb values at w12 (11 patients) compared to w0 (12 patients).

Comparison groups

Floradix mit Eisen v Floradix mit Eisen (baseline)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.0018

Method

t-test, 2-sided

Parameter type

Mean difference (net)

Point estimate

1.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

2.63

Variability estimate

Standard deviation

Dispersion value

1.35

Notes
[1] - Superiority W12 vs. w0. The present study was designed as a prospective exploratory study to demonstrate by means of a trend analysis whether: • the efficacy of both iron preparations is satisfactory in this patient population and whether there are hints for potential differences in the efficacy profile

Baseline difference w12-w0, Ferro sanol duodenal

Statistical analysis description

Changes of Hb values at w12 (9 patients) compared to w0 (12 patients).

Comparison groups

Ferro sanol duodenal mite 50 mg v Ferro sanol duodenal mite 50 mg (baseline)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

= 0.0019

Method

t-test, 2-sided

Parameter type

Mean difference (net)

Point estimate

1.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

1.91

Variability estimate

Standard deviation

Dispersion value

0.84

Notes
[2] - Superiority W12 vs. w0. The present study was designed as a prospective exploratory study to demonstrate by means of a trend analysis whether: • the efficacy of both iron preparations is satisfactory in this patient population and whether there are hints for potential differences in the efficacy profile

Mean group difference w12-w0

Comparison groups

Floradix mit Eisen v Ferro sanol duodenal mite 50 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.374

Method

t-test f unequal var. (Satterthwaite)

Parameter type

Mean difference (net)

Point estimate

0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-0.64

upper limit

1.54

Variability estimate

Standard deviation

Notes
[3] - The primary aim of this was to establish whether a solution is preferable regarding therapeutic effect as compared to a solid oral formulation.

Adverse events

Top of page

Timeframe for reporting adverse events

All adverse events occurring during the clinical study have to be recorded in source documents and CRF. In case an adverse event becomes known to the investigator within 2 weeks after the end of treatment it has still to be reported by the investigator.

Adverse event reporting additional description

All adverse events occurring during the clinical study have to be recorded in the source documents and the CRF. Where they are not based on diagnostic data, such events should be evaluated in standardized fashion through the investigator’s neutral question: “Have you noticed any changes or complaints since your last visit?”

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

15.1

Reporting group title

Floradix mit Eisen

Reporting group description

In the study protocol, an adverse event (AE) was defined as any adverse change from the patients`s condition at screening, whether or not considered to be related to the investigational product.

Reporting group title

Ferro sanol duodenal mite 50 mg

Reporting group description

Serious adverse events	Floradix mit Eisen	Ferro sanol duodenal mite 50 mg
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 13 (15.38%)	1 / 13 (7.69%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Pregnancy, puerperium and perinatal conditions
Postpartum haemorrhage
subjects affected / exposed	1 / 13 (7.69%)	0 / 13 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Premature labour
subjects affected / exposed	0 / 13 (0.00%)	1 / 13 (7.69%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Cervical incompetence
subjects affected / exposed	1 / 13 (7.69%)	0 / 13 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1.7%

Non-serious adverse events	Floradix mit Eisen	Ferro sanol duodenal mite 50 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	9 / 13 (69.23%)	11 / 13 (84.62%)
Vascular disorders
Vascular disorder
subjects affected / exposed	0 / 13 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1
Surgical and medical procedures
Surgical and medicinal procedures
subjects affected / exposed	0 / 13 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1
Pregnancy, puerperium and perinatal conditions
Pregnancy etc.
subjects affected / exposed	3 / 13 (23.08%)	2 / 13 (15.38%)
occurrences all number	4	2
General disorders and administration site conditions
General disorders
subjects affected / exposed	1 / 13 (7.69%)	2 / 13 (15.38%)
occurrences all number	1	2
Reproductive system and breast disorders
Reproductive tract disorder
subjects affected / exposed	1 / 13 (7.69%)	1 / 13 (7.69%)
occurrences all number	1	1
Respiratory, thoracic and mediastinal disorders
Respiratory disorder etc.
subjects affected / exposed	1 / 13 (7.69%)	1 / 13 (7.69%)
occurrences all number	1	1
Injury, poisoning and procedural complications
Injury etc.
subjects affected / exposed	0 / 13 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1
Nervous system disorders
Nervous system disorder
subjects affected / exposed	1 / 13 (7.69%)	0 / 13 (0.00%)
occurrences all number	1	0
Blood and lymphatic system disorders
Blood and lymphatic system disorders
subjects affected / exposed	1 / 13 (7.69%)	0 / 13 (0.00%)
occurrences all number	1	0
Gastrointestinal disorders
Gastrointestinal disorders e.g. Gastroenteritis
subjects affected / exposed	1 / 13 (7.69%)	4 / 13 (30.77%)
occurrences all number	1	4
Skin and subcutaneous tissue disorders
Oedema etc.
subjects affected / exposed	1 / 13 (7.69%)	0 / 13 (0.00%)
occurrences all number	1	0
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder etc.
subjects affected / exposed	0 / 13 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1
Infections and infestations
Infections and infestations e.g. Bacterial abdominal infection;
subjects affected / exposed	4 / 13 (30.77%)	3 / 13 (23.08%)
occurrences all number	4	4
Metabolism and nutrition disorders
Metabolic disorder
subjects affected / exposed	1 / 13 (7.69%)	0 / 13 (0.00%)
occurrences all number	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

29 Mar 2010

Amendment 1 (Protocol v3.0), dated 29 March 2010, was the initially approved version by BfArM and CEC, based on which the study was initiated. The amendment newly introduced the U1 and U2 data from the new-born and a final blood draw at study end.

30 Jul 2010

Amendment 2 (Protocol v4.0), dated 30 July 2010, was introduced to widen the inclusion time window and allow to include patients from gestation week 20 to 28 (both inclusive).

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
A Phase IV, multi-centre, randomized, open label study to investigate the efficacy and safety of Floradix® mit Eisen and ferro sanol® duodenal mite 50 mg in pregnant women with diagnosed iron deficiency

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Baseline change of haemoglobin (Hb) measurements (w12 - w0)

Primary: Baseline change of haemoglobin (Hb) measurements (w12 - w0)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase IV, multi-centre, randomized, open label study to investigate the efficacy and safety of Floradix® mit Eisen and ferro sanol® duodenal mite 50 mg in pregnant women with diagnosed iron deficiency

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Baseline change of haemoglobin (Hb) measurements (w12 - w0)

Primary: Baseline change of haemoglobin (Hb) measurements (w12 - w0)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase IV, multi-centre, randomized, open label study to investigate the efficacy and safety of Floradix® mit Eisen and ferro sanol® duodenal mite 50 mg in pregnant women with diagnosed iron deficiency