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Clinical Trial Results:
The Effect of Tecfidera® (Dimethyl Fumarate, BG00012) on the Gut Microbiota as a Causal Factor for Gastro Intestinal Associated Adverse Events (TECONGUT)

Summary
EudraCT number	2015-001197-18
Trial protocol	NO
Global end of trial date	12 Jun 2017

Results information
Results version number	v1(current)
This version publication date	05 Jan 2019
First version publication date	05 Jan 2019
Other versions

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

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Trial information

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Sponsor protocol code

NOR-BGT-14-10665

ISRCTN number

US NCT number

NCT02471560

WHO universal trial number (UTN)

Sponsor organisation name

Biogen

Sponsor organisation address

250 Binney Street, Cambridge, Massachusetts, United States, 02142

Public contact

Study Medical Director, Biogen, clinicaltrials@biogen.com

Scientific contact

Study Medical Director, Biogen, clinicaltrials@biogen.com

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

12 Jun 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

12 Jun 2017

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary objective of the study was to determine if dimethyl fumarate (DMF) causes changes in the abundance and diversity of commensal microbiota.

Protection of trial subjects

Subjects were treated according to clinical practice; protection of subjects was ensured by health care professional (HCP) as per clinical practice.

Background therapy

Evidence for comparator

Actual start date of recruitment

03 Nov 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Norway: 36

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

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Recruitment details

A total of 38 subjects were screened from 7 sites in Norway.

Screening details

A total of 38 subjects were screened, 1 subject withdrew due to screening failure and 1 subject withdrew informed consent before study start.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Dimethyl Fumarate (DMF)

Arm description

Subjects followed the dosing schedule recommended by summary of product characteristics (SPC) for DMF i.e., 120 milligram (mg) two time daily (BID) orally for 7 days, followed by recommended dose of 240 mg BID.

Arm type

Experimental

Investigational medicinal product name

Dimethyl Fumarate

Investigational medicinal product code

Other name

BG00012

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

DMF 120 mg capsules BID orally for 7 days, followed by recommended dose of 240 mg BID.

Injectable (Multiple Sclerosis Disease Modifying Therapies)

Arm description

Subjects followed administration instructions and dosing schedule recommended in SPC.

Arm type

Experimental

Investigational medicinal product name

Multiple Sclerosis Disease Modifying Therapies (MS DMT)

Investigational medicinal product code

Other name

IFNβ-1a, IFNβ-1b, Glatiramer Acetate

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Administered as recommended by SPC.

Number of subjects in period 1	Dimethyl Fumarate (DMF)	Injectable (Multiple Sclerosis Disease Modifying Therapies)
Started	27	9
Completed	22	9
Not completed	5	0
Adverse Event	3	-
Protocol Deviation	1	-
Lost to follow-up	1	-

Baseline characteristics

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Reporting group title

Dimethyl Fumarate (DMF)

Reporting group description

Reporting group title

Injectable (Multiple Sclerosis Disease Modifying Therapies)

Reporting group description

Subjects followed administration instructions and dosing schedule recommended in SPC.

Reporting group values	Dimethyl Fumarate (DMF)	Injectable (Multiple Sclerosis Disease Modifying Therapies)	Total
Number of subjects	27	9	36
Age Categorical
Units: Subjects
Age Continuous
Units: years
median (inter-quartile range (Q1-Q3))	45 (39 to 52)	44 (33 to 59)	-
Gender Categorical
Units: Subjects
Female	19	7	26
Male	8	2	10

End points

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Reporting group title

Dimethyl Fumarate (DMF)

Reporting group description

Reporting group title

Injectable (Multiple Sclerosis Disease Modifying Therapies)

Reporting group description

Subjects followed administration instructions and dosing schedule recommended in SPC.

Subject analysis set title

DMF Subjects Without GIAE

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects who had received DMF and do not develop gastro-intestinal adverse event (GIAE).

Subject analysis set title

DMF Subjects With GIAE

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects who had received DMF and do develop GIAE.

Primary: Change From Baseline in Gut Microbiota Composition in Subjects pre vs Post Initiation of DMF Treatment at Week 2

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End point title

Change From Baseline in Gut Microbiota Composition in Subjects pre vs Post Initiation of DMF Treatment at Week 2 ^[1]

End point description

End point type

Primary

End point timeframe

Bseline, Week 2

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: Only descriptive data was planned to be reported.

End point values	Dimethyl Fumarate (DMF)	Injectable (Multiple Sclerosis Disease Modifying Therapies)
Number of subjects analysed	27	9
Units: relative abundance of bacterial phyla
median (inter-quartile range (Q1-Q3))
Actinobacteria	0.011 (0.005 to 0.02)	0.024 (0.02 to 0.04)
Bifidobacterium	0.007 (0.001 to 0.01)	0.015 (0.004 to 0.03)
Firmicutes	0.63 (0.52 to 0.77)	0.589 (0.53 to 0.73)
Bacteroidetes	0.195 (0.15 to 0.44)	0.359 (0.21 to 0.45)
Firmicutes:Bacteroidetes-ratio	2.26 (1.2 to 5.4)	1.651 (1.18 to 3.72)
Ruminococcacea	0.32 (0.23 to 0.38)	0.28 (0.17 to 0.35)
Faecalibacterium	0.055 (0.03 to 0.09)	0.06 (0.04 to 0.10)
Bacteroides	0.14 (0.09 to 0.30)	0.117 (0.09 to 0.24)

No statistical analyses for this end point

Primary: Change From Baseline in Gut Microbiota Composition in Subjects pre vs Post Initiation of DMF Treatment at Week 12

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End point title

Change From Baseline in Gut Microbiota Composition in Subjects pre vs Post Initiation of DMF Treatment at Week 12 ^[2]

End point description

End point type

Primary

End point timeframe

Baseline, Week 12

Notes
[2] - 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: Only descriptive data was planned to be reported.

End point values	Dimethyl Fumarate (DMF)	Injectable (Multiple Sclerosis Disease Modifying Therapies)
Number of subjects analysed	27	9
Units: relative abundance of bacterial phyla
median (inter-quartile range (Q1-Q3))
Actinobacteria	0.016 (0.01 to 0.04)	0.02 (0.008 to 0.03)
Bifidobacterium	0.012 (0.002 to 0.02)	0.011 (0.004 to 0.03)
Firmicutes	0.679 (0.56 to 0.78)	0.659 (0.46 to 0.72)
Bacteroidetes	0.246 (0.13 to 0.35)	0.292 (0.23 to 0.49)
Firmicutes:Bacteroidetes-ratio	2.685 (1.51 to 6.35)	2.253 (1.10 to 3.17)
Ruminococcacea	0.32 (0.27 to 0.41)	0.25 (0.18 to 0.38)
Faecalibacterium	0.067 (0.04 to 0.11)	0.06 (0.05 to 0.08)
Bacteroides	0.14 (0.07 to 0.23)	0.165 (0.09 to 0.28)

No statistical analyses for this end point

Primary: Change From Baseline in Shannon Index in Subjects pre vs Post Initiation of DMF Treatment at Week 2

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End point title

Change From Baseline in Shannon Index in Subjects pre vs Post Initiation of DMF Treatment at Week 2 ^[3]

End point description

Shannon diversity index is a quantitative measure that reflects how many different types (such as species) are in a dataset (a community), and simultaneously takes into account how evenly the basic entities (such as individuals) are distributed among those types. A community with only one species would have Shannon’s index of 0. The higher the index, the more diverse a community.

End point type

Primary

End point timeframe

Baseline, Week 2

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: Only descriptive data was planned to be reported.

End point values	Dimethyl Fumarate (DMF)	Injectable (Multiple Sclerosis Disease Modifying Therapies)
Number of subjects analysed	27	9
Units: shannon's diversity index
median (inter-quartile range (Q1-Q3))	6.54 (6.03 to 6.76)	6.53 (5.80 to 7.09)

No statistical analyses for this end point

Primary: Change From Baseline in Shannon Index in Subjects pre vs Post Initiation of DMF Treatment at Week 12

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End point title

Change From Baseline in Shannon Index in Subjects pre vs Post Initiation of DMF Treatment at Week 12 ^[4]

End point description

End point type

Primary

End point timeframe

Baseline, Week 12

Notes
[4] - 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: Only descriptive data was planned to be reported.

End point values	Dimethyl Fumarate (DMF)	Injectable (Multiple Sclerosis Disease Modifying Therapies)
Number of subjects analysed	27	9
Units: shannon's diversity index
median (inter-quartile range (Q1-Q3))	6.49 (6.08 to 6.73)	6.74 (5.89 to 7.08)

No statistical analyses for this end point

Secondary: Change From Baseline in Gut Microbiota composition Between DMF Treated Subjects That do or do not Develop Gastro-intestinal (GI) Adverse Evenrs (AEs) as Measured by an Increase in the Gastrointestinal Symptom Rating Scale (GSRS) Score at Week 2 and 12

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End point title

Change From Baseline in Gut Microbiota composition Between DMF Treated Subjects That do or do not Develop Gastro-intestinal (GI) Adverse Evenrs (AEs) as Measured by an Increase in the Gastrointestinal Symptom Rating Scale (GSRS) Score at Week 2 and 12

End point description

GSRS is a self-reported questionnaire regarding GI symptoms comprising 15 items scored on a 7-point Likert scale. The 15 items can be grouped in 5 dimensions 1) abdominal pain (abdominal pain, gastric hunger pain, and nausea) 2) reflux (heartburn and acid regurgitation) 3) indigestion (borborygmus, bloating, eructation, and increased flatus) 4) diarrhea (diarrhea, loose stools, and urgency) and 5) constipation (constipation, hard stools, incomplete evacuation). A GI AE will be defined as an at least 2 point (>=2) increase from baseline in total score of any of the 5 dimensions in the GSRS. (maximum score per dimension is 3 items x 7 points = 21). Here, 'n' signifies that number of subjects evaluated for the specified bacterial composition.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 12

End point values	DMF Subjects Without GIAE	DMF Subjects With GIAE
Number of subjects analysed	11 ^[5]	10 ^[6]
Units: relative abundance of bacterial phyla
median (inter-quartile range (Q1-Q3))
Actinobacteria: Baseline for Week 2 (n =11, 10)	0.016 (0.012 to 0.032)	0.022 (0.008 to 0.045)
Actinobacteria: Change at Week 2 (n =11, 10)	0.011 (0.005 to 0.022)	0.011 (0.003 to 0.024)
Actinobacteria: Baseline for Week 12 (n =10, 10)	0.03 (0.013 to 0.046)	0.01 (0.004 to 0.024)
Actinobacteria: Change at Week 12 (n =10, 10)	0.024 (0.009 to 0.048)	0.011 (0.004 to 0.03)
Bifidobacterium: Baseline for Week 2 (n =11, 10)	0.011 (0.006 to 0.022)	0.012 (0.005 to 0.038)
Bifidobacterium: Change at Week 2 (n =11, 10)	0.008 (0.003 to 0.014)	0.005 (0 to 0.015)
Bifidobacterium: Baseline for Week 12 (n =10, 10)	0.016 (0.007 to 0.04)	0.007 (0.002 to 0.018)
Bifidobacterium: Change at Week 12 (n =10, 10)	0.015 (0.004 to 0.028)	0.008 (0.001 to 0.027)
Firmicutes: Baseline for Week 2 (n =11, 10)	0.546 (0.509 to 0.734)	0.728 (0.536 to 0.787)
Firmicutes: Change at Week 2 (n =11, 10)	0.622 (0.533 to 0.799)	0.686 (0.515 to 0.782)
Firmicutes: Baseline for Week 12 (n =10, 10)	0.632 (0.539 to 0.724)	0.702 (0.521 to 0.843)
Firmicutes: Change at Week 12 (n =10, 10)	0.685 (0.597 to 0.784)	0.715 (0.563 to 0.866)
Bacteroidetes: Baseline for Week 2 (n =11, 10)	0.388 (0.184 to 0.424)	0.188 (0.151 to 0.294)
Bacteroidetes: Change at Week 2 (n =11, 10)	0.311 (0.138 to 0.437)	0.192 (0.145 to 0.368)
Bacteroidetes: Baseline for Week 12 (n =10, 10)	0.319 (0.187 to 0.396)	0.22 (0.089 to 0.426)
Bacteroidetes: Change at Week 12 (n =10, 10)	0.245 (0.151 to 0.29)	0.221 (0.078 to 0.405)
Faecalibacterium: Baseline for Week 2 (n =11, 10)	0.036 (0.025 to 0.057)	0.057 (0.033 to 0.094)
Faecalibacterium: Change at Week 2 (n =11, 10)	0.055 (0.037 to 0.072)	0.058 (0.024 to 0.139)
Faecalibacterium: Baseline for Week 12 (n =10, 10)	0.044 (0.025 to 0.071)	0.052 (0.027 to 0.094)
Faecalibacterium: Change at Week 12 (n =10, 10)	0.063 (0.035 to 0.117)	0.071 (0.051 to 0.119)
Bacteroides: Baseline for Week 2 (n =11, 10)	0.304 (0.125 to 0.352)	0.115 (0.065 to 0.162)
Bacteroides: Change at Week 2 (n =11, 10)	0.244 (0.088 to 0.379)	0.14 (0.052 to 0.26)
Bacteroides: Baseline for Week 12 (n =10, 10)	0.25 (0.124 to 0.321)	0.104 (0.028 to 0.311)
Bacteroides: Change at Week 12 (n =10, 10)	0.152 (0.074 to 0.224)	0.107 (0.019 to 0.261)

Notes
[5] - Number of subjects analysed is the number of subjects evaluated for this endpoint.
[6] - Number of subjects analysed is the number of subjects evaluated for this endpoint.

No statistical analyses for this end point

Secondary: Change From Baseline in Gut Microbiota Composition in Subjects Treated With DMF Compared to Subjects Treated With an Alternative MS DMT at Week 2 and 12

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End point title

Change From Baseline in Gut Microbiota Composition in Subjects Treated With DMF Compared to Subjects Treated With an Alternative MS DMT at Week 2 and 12

End point description

Here, 'n' signifies the number of subjects evaluated for specified bacterial composition.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 12

End point values	Dimethyl Fumarate (DMF)	Injectable (Multiple Sclerosis Disease Modifying Therapies)
Number of subjects analysed	21 ^[7]	9 ^[8]
Units: delta values of relative abundance
median (inter-quartile range (Q1-Q3))
Change in Actinobacteria at Week 2 (n =21, 9)	-0.006 (-0.026 to 0.002)	-0.001 (-0.008 to 0.016)
Change in Actinobacteria at Week 12 (n =20, 9)	0 (-0.02 to 0.022)	-0.002 (-0.02 to 0.002)
Change in Bifidobacterium at Week 2 (n =21, 9)	-0.002 (-0.013 to 0.001)	-0.002 (-0.012 to 0.011)
Change in Bifidobacterium at Week 12 (n =20, 9)	0.001 (-0.015 to 0.013)	-0.003 (-0.023 to 0.001)
Change in Firmicutes at Week 2 (n =21, 9)	0.011 (-0.06 to 0.078)	0.001 (-0.069 to 0.032)
Change in Firmicutes at Week 12 (n =20, 9)	0.048 (0.002 to 0.088)	-0.012 (-0.032 to 0.066)
Change in Bacteroidetes at Week 2 (n =21, 9)	-0.014 (-0.062 to 0.053)	0.025 (-0.031 to 0.066)
Change in Bacteroidetes at Week 12 (n =20, 9)	-0.045 (-0.096 to -0.005)	0.011 (-0.061 to 0.061)
Change in Faecalibacterium at Week 2 (n =21, 9)	0.004 (-0.009 to 0.033)	-0.018 (-0.039 to 0.003)
Change in Faecalibacterium at Week 12 (n =20, 9)	0.021 (-0.001 to 0.046)	-0.007 (-0.035 to 0.011)
Change in Bacteroides at Week 2 (n =21, 9)	-0.004 (-0.05 to 0.045)	0.008 (-0.049 to 0.051)
Change in Bacteroides at Week 12 (n =20, 9)	-0.046 (-0.066 to -0.004)	-0.005 (-0.017 to 0.054)

Notes
[7] - Number of subjects analysed is the number of subjects evaluated for this endpoint.
[8] - Number of subjects analysed is the number of subjects evaluated for this endpoint.

No statistical analyses for this end point

Secondary: Baseline Differences in the Gut Microbiota composition Between DMF Treated Subjects That do or do not Develop GI AEs at Week 2 and 12

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End point title

Baseline Differences in the Gut Microbiota composition Between DMF Treated Subjects That do or do not Develop GI AEs at Week 2 and 12

End point description

Here, 'n' signifies the number of subjects evaluated for specified bacterial composition.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 12

End point values	DMF Subjects Without GIAE	DMF Subjects With GIAE
Number of subjects analysed	12	12
Units: relative abundance of bacterial phyla
median (inter-quartile range (Q1-Q3))
Change in Actinobacteria at Week 2 (n =12, 12)	0.015 (0.012 to 0.031)	0.021 (0.008 to 0.035)
Change in Actinobacteria at Week 12 (n =10, 11)	0.03 (0.013 to 0.046)	0.011 (0.004 to 0.023)
Change in Bifidobacterium at Week 2 (n =12, 12)	0.011 (0.005 to 0.02)	0.012 (0.003 to 0.031)
Change in Bifidobacterium at Week 12 (n =10, 11)	0.016 (0.007 to 0.04)	0.008 (0.002 to 0.017)
Change in Firmicutes at Week 2 (n =12, 12)	0.545 (0.51 to 0.724)	0.708 (0.528 to 0.767)
Change in Firmicutes at Week 12 (n =10, 11)	0.632 (0.539 to 0.724)	0.734 (0.524 to 0.835)
Change in Bacteroidetes at Week 2 (n =12, 12)	0.39 (0.186 to 0.466)	0.206 (0.171 to 0.372)
Change in Bacteroidetes at Week 12 (n =10, 11)	0.319 (0.187 to 0.396)	0.184 (0.092 to 0.424)
Change in Faecalibacterium at Week 2 (n =12, 12)	0.037 (0.025 to 0.063)	0.056 (0.031 to 0.088)
Change in Faecalibacterium at Week 12 (n =10, 11)	0.044 (0.025 to 0.071)	0.039 (0.029 to 0.093)
Change in Bacteroides at Week 2 (n =12, 12)	0.308 (0.125 to 0.408)	0.124 (0.078 to 0.21)
Change in Bacteroides at Week 12 (n =10, 11)	0.25 (0.124 to 0.321)	0.108 (0.031 to 0.306)

No statistical analyses for this end point

Secondary: Change From Baseline in the Gut Microbiota Composition of DMF Treated Subjects After Resolution of GI AEs vs. During GI AE Occurrences at Week 2 and 12

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End point title

Change From Baseline in the Gut Microbiota Composition of DMF Treated Subjects After Resolution of GI AEs vs. During GI AE Occurrences at Week 2 and 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 12

End point values	Dimethyl Fumarate (DMF)	Injectable (Multiple Sclerosis Disease Modifying Therapies)
Number of subjects analysed	0 ^[9]	0 ^[10]
Units: relative abundance of bacterial phyla
median (standard deviation)	( )	( )

Notes
[9] - Data was not collected for the endpoint due to low number of subjects analysed.
[10] - Data was not collected for the endpoint due to low number of subjects analysed.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From start to last visit (Up to Week 12)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Multiple Sclerosis Disease Modifying Therapies (MS DMT)

Reporting group description

Subjects followed administration instructions and dosing schedule recommended in SPC.

Reporting group title

Dimethyl Fumarate (DMF)

Reporting group description

Serious adverse events	Multiple Sclerosis Disease Modifying Therapies (MS DMT)	Dimethyl Fumarate (DMF)
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 9 (11.11%)	1 / 27 (3.70%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Nervous system disorders
Relapsing-remitting multiple sclerosis
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple sclerosis relapse
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Optic neuritis
subjects affected / exposed	1 / 9 (11.11%)	0 / 27 (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: 0%

Non-serious adverse events	Multiple Sclerosis Disease Modifying Therapies (MS DMT)	Dimethyl Fumarate (DMF)
Total subjects affected by non serious adverse events
subjects affected / exposed	8 / 9 (88.89%)	15 / 27 (55.56%)
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	1 / 9 (11.11%)	0 / 27 (0.00%)
occurrences all number	1	0
Vascular disorders
Flushing
subjects affected / exposed	0 / 9 (0.00%)	4 / 27 (14.81%)
occurrences all number	0	4
Hot Flush
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
Hypertension
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
Nervous system disorders
Monoparesis
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
General disorders and administration site conditions
Injection site rash
subjects affected / exposed	1 / 9 (11.11%)	0 / 27 (0.00%)
occurrences all number	1	0
Pain
subjects affected / exposed	1 / 9 (11.11%)	0 / 27 (0.00%)
occurrences all number	1	0
Pyrexia
subjects affected / exposed	1 / 9 (11.11%)	0 / 27 (0.00%)
occurrences all number	1	0
Hunger
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
Gastrointestinal disorders
Nausea
subjects affected / exposed	0 / 9 (0.00%)	4 / 27 (14.81%)
occurrences all number	0	3
Abdominal pain
subjects affected / exposed	0 / 9 (0.00%)	2 / 27 (7.41%)
occurrences all number	0	2
Diarrhoea
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
Lip oedema
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
Vomiting
subjects affected / exposed	0 / 9 (0.00%)	2 / 27 (7.41%)
occurrences all number	0	2
Abdominal discomfort
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
Constipation
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
Dermatitis contact
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
Psychiatric disorders
Depression
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	1 / 9 (11.11%)	0 / 27 (0.00%)
occurrences all number	1	0
Infections and infestations
Influenza
subjects affected / exposed	1 / 9 (11.11%)	0 / 27 (0.00%)
occurrences all number	1	0
Gastroenteritis
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
Urinary tract infection
subjects affected / exposed	0 / 9 (0.00%)	1 / 27 (3.70%)
occurrences all number	0	1
Sinusitis
subjects affected / exposed	0 / 9 (0.00%)	2 / 27 (7.41%)
occurrences all number	0	2
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 9 (11.11%)	0 / 27 (0.00%)
occurrences all number	1	0

More information

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
12 Jun 2017	Due to poor recruitment level in the study, it was decided to stop recruitment before the target number of subjects was reached.	-

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

None reported

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Clinical trials

Clinical Trial Results:
The Effect of Tecfidera® (Dimethyl Fumarate, BG00012) on the Gut Microbiota as a Causal Factor for Gastro Intestinal Associated Adverse Events (TECONGUT)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline in Gut Microbiota Composition in Subjects pre vs Post Initiation of DMF Treatment at Week 2

Primary: Change From Baseline in Gut Microbiota Composition in Subjects pre vs Post Initiation of DMF Treatment at Week 2

Primary: Change From Baseline in Gut Microbiota Composition in Subjects pre vs Post Initiation of DMF Treatment at Week 12

Primary: Change From Baseline in Gut Microbiota Composition in Subjects pre vs Post Initiation of DMF Treatment at Week 12

Primary: Change From Baseline in Shannon Index in Subjects pre vs Post Initiation of DMF Treatment at Week 2

Primary: Change From Baseline in Shannon Index in Subjects pre vs Post Initiation of DMF Treatment at Week 2

Primary: Change From Baseline in Shannon Index in Subjects pre vs Post Initiation of DMF Treatment at Week 12

Primary: Change From Baseline in Shannon Index in Subjects pre vs Post Initiation of DMF Treatment at Week 12

Secondary: Change From Baseline in Gut Microbiota composition Between DMF Treated Subjects That do or do not Develop Gastro-intestinal (GI) Adverse Evenrs (AEs) as Measured by an Increase in the Gastrointestinal Symptom Rating Scale (GSRS) Score at Week 2 and 12

Secondary: Change From Baseline in Gut Microbiota composition Between DMF Treated Subjects That do or do not Develop Gastro-intestinal (GI) Adverse Evenrs (AEs) as Measured by an Increase in the Gastrointestinal Symptom Rating Scale (GSRS) Score at Week 2 and 12

Secondary: Change From Baseline in Gut Microbiota Composition in Subjects Treated With DMF Compared to Subjects Treated With an Alternative MS DMT at Week 2 and 12

Secondary: Change From Baseline in Gut Microbiota Composition in Subjects Treated With DMF Compared to Subjects Treated With an Alternative MS DMT at Week 2 and 12

Secondary: Baseline Differences in the Gut Microbiota composition Between DMF Treated Subjects That do or do not Develop GI AEs at Week 2 and 12

Secondary: Baseline Differences in the Gut Microbiota composition Between DMF Treated Subjects That do or do not Develop GI AEs at Week 2 and 12

Secondary: Change From Baseline in the Gut Microbiota Composition of DMF Treated Subjects After Resolution of GI AEs vs. During GI AE Occurrences at Week 2 and 12

Secondary: Change From Baseline in the Gut Microbiota Composition of DMF Treated Subjects After Resolution of GI AEs vs. During GI AE Occurrences at Week 2 and 12

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: The Effect of Tecfidera® (Dimethyl Fumarate, BG00012) on the Gut Microbiota as a Causal Factor for Gastro Intestinal Associated Adverse Events (TECONGUT)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline in Gut Microbiota Composition in Subjects pre vs Post Initiation of DMF Treatment at Week 2

Primary: Change From Baseline in Gut Microbiota Composition in Subjects pre vs Post Initiation of DMF Treatment at Week 2

Primary: Change From Baseline in Gut Microbiota Composition in Subjects pre vs Post Initiation of DMF Treatment at Week 12

Primary: Change From Baseline in Gut Microbiota Composition in Subjects pre vs Post Initiation of DMF Treatment at Week 12

Primary: Change From Baseline in Shannon Index in Subjects pre vs Post Initiation of DMF Treatment at Week 2

Primary: Change From Baseline in Shannon Index in Subjects pre vs Post Initiation of DMF Treatment at Week 2

Primary: Change From Baseline in Shannon Index in Subjects pre vs Post Initiation of DMF Treatment at Week 12

Primary: Change From Baseline in Shannon Index in Subjects pre vs Post Initiation of DMF Treatment at Week 12

Secondary: Change From Baseline in Gut Microbiota composition Between DMF Treated Subjects That do or do not Develop Gastro-intestinal (GI) Adverse Evenrs (AEs) as Measured by an Increase in the Gastrointestinal Symptom Rating Scale (GSRS) Score at Week 2 and 12

Secondary: Change From Baseline in Gut Microbiota composition Between DMF Treated Subjects That do or do not Develop Gastro-intestinal (GI) Adverse Evenrs (AEs) as Measured by an Increase in the Gastrointestinal Symptom Rating Scale (GSRS) Score at Week 2 and 12

Secondary: Change From Baseline in Gut Microbiota Composition in Subjects Treated With DMF Compared to Subjects Treated With an Alternative MS DMT at Week 2 and 12

Secondary: Change From Baseline in Gut Microbiota Composition in Subjects Treated With DMF Compared to Subjects Treated With an Alternative MS DMT at Week 2 and 12

Secondary: Baseline Differences in the Gut Microbiota composition Between DMF Treated Subjects That do or do not Develop GI AEs at Week 2 and 12

Secondary: Baseline Differences in the Gut Microbiota composition Between DMF Treated Subjects That do or do not Develop GI AEs at Week 2 and 12

Secondary: Change From Baseline in the Gut Microbiota Composition of DMF Treated Subjects After Resolution of GI AEs vs. During GI AE Occurrences at Week 2 and 12

Secondary: Change From Baseline in the Gut Microbiota Composition of DMF Treated Subjects After Resolution of GI AEs vs. During GI AE Occurrences at Week 2 and 12

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
The Effect of Tecfidera® (Dimethyl Fumarate, BG00012) on the Gut Microbiota as a Causal Factor for Gastro Intestinal Associated Adverse Events (TECONGUT)