Download PDF

Clinical Trial Results:
Double-blind, randomised clinical study comparing efficacy and safety of Miconazole 2% Fluprednidene 0.1% Cream (Test) vs. Vobaderm® Cream (Reference) vs. Vehicle in patients with moderate to severely inflamed candidiasis of the skin.

Summary
EudraCT number	2015-005707-92
Trial protocol	DE
Global end of trial date	10 Aug 2018

Results information
Results version number	v1(current)
This version publication date	06 Apr 2022
First version publication date	06 Apr 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

16-03/MicoFlu-C

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Dermapharm AG

Sponsor organisation address

Lil-Dagover-Ring 7, Gruenwald, Germany, 82031

Public contact

Clinical Research Department, Dermapharm AG, +49 89641860, Clinicaltrials.Dermapharm@dermapharm.com

Scientific contact

Clinical Research Department, Dermapharm AG, +49 89641860, Clinicaltrials.Dermapharm@dermapharm.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

23 Apr 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

10 Aug 2018

Global end of trial reached?

Yes

Global end of trial date

10 Aug 2018

Was the trial ended prematurely?

Main objective of the trial

Assessment of efficacy and safety of a new cream with miconazole 2 % and fluprednidene 0.1 % in comparison with the approved preparation Vobaderm® Cream and the underlying vehicle in patients with moderate to severely inflamed candidiasis of the skin.

Protection of trial subjects

There were no specific measures necessary.

Background therapy

There was no background therapy.

Evidence for comparator

The trial aimed to show comparable efficacy and safety to the comparator in order to obtain a generic marketing authorization for the test product.

Actual start date of recruitment

06 Jan 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 340

Worldwide total number of subjects

340

EEA total number of subjects

340

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)

187

From 65 to 84 years

140

85 years and over

Subject disposition

Top of page

Recruitment details

21 study centers in Germany; first patient first visit: 19 January 2017; last patient last visit: 10 August 2018

Screening details

Main criteria for inclusion: Women and men ≥ 18 years of age; Diagnosis of candidiasis of the skin based on clinical symptoms; Positive mycological result of a swab revealing at least a moderate number of fungi, microscopically proven; Sum score of all clinical parameters ≥ 7; At least moderate severity of parameters erythema and exudation

Period 1 title

Treatment Period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Blinding implementation details

The tubes containing the study medications were neutral white. The attached labels were identical for all preparations, but they differed in terms of the specified week of treatment (i.e. “week 1” or “week 2”). This applied to all three treatment arms. All study medications were indistinguishable in terms of appearance. The random code was transferred to the data base not before the following actions were completed: data base closure, finalisation of the SAP, and a Blind Data Review Report.

Are arms mutually exclusive

Yes

MicoFlu-C

Arm description

Test product

Arm type

Experimental

Investigational medicinal product name

Miconazole 2%_Fluprednidene 0.1% Cream

Investigational medicinal product code

D07XB03

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

In the treatment period: Application twice daily as a thin film on the affected area.

Vobaderm

Arm description

Reference Product

Arm type

Active comparator

Investigational medicinal product name

Vobaderm Cream

Investigational medicinal product code

D07XB03

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

In the treatment period: Application twice daily as a thin film on the affected area.

Vehicle

Arm description

Vehicle of Test product

Arm type

Placebo

Investigational medicinal product name

Vehicle

Investigational medicinal product code

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

In the treatment period: Application twice daily as a thin film on the affected area.

Number of subjects in period 1	MicoFlu-C	Vobaderm	Vehicle
Started	116	118	106
Completed	105	108	96
Not completed	11	10	10
Consent withdrawn by subject	3	3	2
Adverse event, non-fatal	1	1	1
Technical-logistic reasons	1	1	2
Lost to follow-up	1	-	-
Strong worsening of symptoms in FU	3	4	1
Lack of efficacy	1	1	4
Protocol deviation	1	-	-

Baseline characteristics

Top of page

Reporting group title

Treatment Period

Reporting group description

Reporting group values	Treatment Period	Total
Number of subjects	340	340
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	187	187
From 65-84 years	140	140
85 years and over	13	13
Gender categorical
Units: Subjects
Female	173	173
Male	167	167

Subject analysis set title

Safety data set

Subject analysis set type

Safety analysis

Subject analysis set description

Includes all randomised patients who had administered the study medication at least once and who provided at least one safety related outcome.

Subject analysis set title

ITT

Subject analysis set type

Intention-to-treat

Subject analysis set description

Includes all patients of the safety data set who complied with the study diagnosis (according to the associated inclusion criteria) and provided at least one post-baseline value to ensure the evaluation of the primary efficacy variable.

Subject analysis set title

Subject analysis set type

Per protocol

Subject analysis set description

Includes all patients of the ITT data set who do not exhibit any major protocol violation.

Subject analysis sets values	Safety data set	ITT	PP
Number of subjects	340	337	302
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)	187	186	168
From 65-84 years	140	138	123
85 years and over	13	13	11
Age continuous
Units:
	±	±	±
Gender categorical
Units: Subjects
Female	173	171	153
Male	167	166	149

End points

Top of page

Reporting group title

MicoFlu-C

Reporting group description

Test product

Reporting group title

Vobaderm

Reporting group description

Reference Product

Reporting group title

Vehicle

Reporting group description

Vehicle of Test product

Subject analysis set title

Safety data set

Subject analysis set type

Safety analysis

Subject analysis set description

Includes all randomised patients who had administered the study medication at least once and who provided at least one safety related outcome.

Subject analysis set title

ITT

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Subject analysis set type

Per protocol

Subject analysis set description

Includes all patients of the ITT data set who do not exhibit any major protocol violation.

Primary: Treatment effect

Top of page

End point title

Treatment effect

End point description

The primary efficacy variable is treatment success (yes, no) at Visit 4 (LOCF) (i.e. the final examination visit; “test-of-cure”). Treatment success is defined as fulfilment of clinical success (defined as fulfilment of both, sum score of clinical parameters ≤ 2 and all individual clinical scores ≤ 1) and mycological success (defined as negative microscopical testing, i.e. a score value of 0 = no fungi to be seen).

End point type

Primary

End point timeframe

Start of treatment (visit 1) to "test of cure" (visit 4); with 2 weeks treatment (1 week with the trial medication + 1 week follow-up treatment) + 1 week follow-up without treatment.

End point values	MicoFlu-C	Vobaderm	Vehicle	ITT	PP
Number of subjects analysed	101	106	106	337	302
Units: Percentage
number (not applicable)	65	65	50	190	179

Analysis of efficacy

Statistical analysis description

The primary objective of this study was to show non-inferiority of MicoFlu-C in comparison to Vobaderm with respect to the primary efficacy variable. The non-inferiority margin was set to Δ = 0.2 (20%).

Comparison groups

MicoFlu-C v Vobaderm v PP

Number of subjects included in analysis

509

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

Mean difference (final values)

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-11.09

upper limit

17.16

Superiority of Test over Vehicle

Statistical analysis description

In order to verify assay sensitivity of the study, superiority of the two active preparations over the vehicle was tested by means of two-sided significance tests with α = 0.05. The primary test of superiority was carried out for the ITT data set.

Comparison groups

MicoFlu-C v Vehicle v ITT

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0601

Method

Fisher exact

Confidence interval

Superiority of Reference over Vehicle

Statistical analysis description

Comparison groups

Vobaderm v Vehicle v ITT

Number of subjects included in analysis

549

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0431

Method

Fisher exact

Confidence interval

Adverse events

Top of page

Timeframe for reporting adverse events

From the inclusion visit (V1, day 0) to the final visit (V4, day 21, "test of cure").

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

MicoFlu-C

Reporting group description

Test product

Reporting group title

Vobaderm

Reporting group description

Reference Product

Reporting group title

Vehicle

Reporting group description

Vehicle of Test product

Serious adverse events	MicoFlu-C	Vobaderm	Vehicle
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 116 (0.86%)	0 / 118 (0.00%)	1 / 106 (0.94%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 116 (0.00%)	0 / 118 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
Anaphylactoid reaction
subjects affected / exposed	1 / 116 (0.86%)	0 / 118 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Peritonitis
subjects affected / exposed	0 / 116 (0.00%)	0 / 118 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0.05%

Non-serious adverse events	MicoFlu-C	Vobaderm	Vehicle
Total subjects affected by non serious adverse events
subjects affected / exposed	11 / 116 (9.48%)	10 / 118 (8.47%)	7 / 106 (6.60%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 116 (0.00%)	1 / 118 (0.85%)	0 / 106 (0.00%)
occurrences all number	0	1	0
Fibroma
subjects affected / exposed	1 / 116 (0.86%)	0 / 118 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0
Rectal adenoma
subjects affected / exposed	0 / 116 (0.00%)	0 / 118 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	1
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 116 (0.00%)	1 / 118 (0.85%)	0 / 106 (0.00%)
occurrences all number	0	1	0
Skin laceration
subjects affected / exposed	0 / 116 (0.00%)	1 / 118 (0.85%)	0 / 106 (0.00%)
occurrences all number	0	1	0
Traumatic haematoma
subjects affected / exposed	1 / 116 (0.86%)	0 / 118 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0
Vascular disorders
Flushing
subjects affected / exposed	0 / 116 (0.00%)	0 / 118 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	1
Surgical and medical procedures
Tooth extraction
subjects affected / exposed	1 / 116 (0.86%)	0 / 118 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0
Nervous system disorders
Headache
subjects affected / exposed	1 / 116 (0.86%)	1 / 118 (0.85%)	2 / 106 (1.89%)
occurrences all number	1	1	2
Neuralgia
subjects affected / exposed	1 / 116 (0.86%)	0 / 118 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0
General disorders and administration site conditions
Application site eczema
subjects affected / exposed	1 / 116 (0.86%)	0 / 118 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0
Chills
subjects affected / exposed	0 / 116 (0.00%)	0 / 118 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	1
Gastrointestinal disorders
Duodenitis
subjects affected / exposed	0 / 116 (0.00%)	0 / 118 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	1
Nausea
subjects affected / exposed	0 / 116 (0.00%)	1 / 118 (0.85%)	0 / 106 (0.00%)
occurrences all number	0	1	0
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	0 / 116 (0.00%)	1 / 118 (0.85%)	0 / 106 (0.00%)
occurrences all number	0	1	0
Pleural effusion
subjects affected / exposed	0 / 116 (0.00%)	0 / 118 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	1
Skin and subcutaneous tissue disorders
Dermatitis contact
subjects affected / exposed	0 / 116 (0.00%)	1 / 118 (0.85%)	0 / 106 (0.00%)
occurrences all number	0	1	0
Eczema
subjects affected / exposed	0 / 116 (0.00%)	1 / 118 (0.85%)	0 / 106 (0.00%)
occurrences all number	0	1	0
Hyperhidrosis
subjects affected / exposed	0 / 116 (0.00%)	1 / 118 (0.85%)	0 / 106 (0.00%)
occurrences all number	0	1	0
Lichen planus
subjects affected / exposed	1 / 116 (0.86%)	0 / 118 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0
Papule
subjects affected / exposed	0 / 116 (0.00%)	0 / 118 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	1
Infections and infestations
Abscess
subjects affected / exposed	0 / 116 (0.00%)	0 / 118 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	1
Hordeolum
subjects affected / exposed	1 / 116 (0.86%)	0 / 118 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0
Infected bite
subjects affected / exposed	0 / 116 (0.00%)	1 / 118 (0.85%)	0 / 106 (0.00%)
occurrences all number	0	1	0
Nasopharyngitis
subjects affected / exposed	5 / 116 (4.31%)	0 / 118 (0.00%)	1 / 106 (0.94%)
occurrences all number	5	0	1
Oral herpes
subjects affected / exposed	0 / 116 (0.00%)	1 / 118 (0.85%)	0 / 106 (0.00%)
occurrences all number	0	1	0
Pulpitis dental
subjects affected / exposed	1 / 116 (0.86%)	0 / 118 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0
Urinary tract infection
subjects affected / exposed	0 / 116 (0.00%)	1 / 118 (0.85%)	0 / 106 (0.00%)
occurrences all number	0	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? No

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:
Double-blind, randomised clinical study comparing efficacy and safety of Miconazole 2% Fluprednidene 0.1% Cream (Test) vs. Vobaderm® Cream (Reference) vs. Vehicle in patients with moderate to severely inflamed candidiasis of the skin.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Treatment effect

Primary: Treatment effect

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: Double-blind, randomised clinical study comparing efficacy and safety of Miconazole 2% Fluprednidene 0.1% Cream (Test) vs. Vobaderm® Cream (Reference) vs. Vehicle in patients with moderate to severely inflamed candidiasis of the skin.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Treatment effect

Primary: Treatment effect

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Double-blind, randomised clinical study comparing efficacy and safety of Miconazole 2% Fluprednidene 0.1% Cream (Test) vs. Vobaderm® Cream (Reference) vs. Vehicle in patients with moderate to severely inflamed candidiasis of the skin.