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Clinical Trial Results:
Double-blind, randomised clinical study comparing efficacy and safety of Ciclopirox Olamine Cream 10 mg/g (Test) vs. Batrafen® Cream (Reference) vs. Vehicle in patients with skin mycoses

Summary
EudraCT number	2018-001633-41
Trial protocol	DE
Global end of trial date	08 Jun 2021

Results information
Results version number	v1(current)
This version publication date	08 Jun 2022
First version publication date	08 Jun 2022
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

18-01/Cic-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

20 Apr 2022

Is this the analysis of the primary completion data?

Yes

Primary completion date

08 Jun 2021

Global end of trial reached?

Yes

Global end of trial date

08 Jun 2021

Was the trial ended prematurely?

Main objective of the trial

Evaluation of the efficiacy and safety of a new creme containing 10 mg/g Ciclopirox Olamine vs. the originator Batrafen® Cream (Reference) vs. vehicle in patients with skin mycoses

Protection of trial subjects

There were no specific measures necessary.

Background therapy

There was no background therapy.

Evidence for comparator

The comparator contains the same ingredients in the same concentration as the test product and has a marketing license for the study indication.

Actual start date of recruitment

18 Jul 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 403

Worldwide total number of subjects

403

EEA total number of subjects

403

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)

296

From 65 to 84 years

105

85 years and over

Subject disposition

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Recruitment details

14 study centers in Germany; first patient first visit: 05 August 2019; last patient last visit: 08 June 2021

Screening details

Main criteria for inclusion: Women and men ≥ 18 years of age; Diagnosis of skin mycosis confirmed by a positive microscopic native preparation in 30% potassium hydroxide (KOH); sum score of the parameters pruritus, burning/stinging, erythema, fissuring/cracking, scaling, and maceration up to a total score value of ≥ 6 (equal to moderate severity)

Period 1 title

Treatment Period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Monitor, Data analyst, Subject

Blinding implementation details

The tubes containing the study medications were neutral white. The attached labels were identical for all three preparations. All three 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, a Blind Data Review (BDR) and the agreement between sponsor and study statistician upon the definition of the analysis data sets (fixed in a BDR Report).

Are arms mutually exclusive

Yes

Cic-C

Arm description

Test product

Arm type

Experimental

Investigational medicinal product name

Ciclopirox Olamin Cream 10 mg/g

Investigational medicinal product code

D01AE14

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

Application twice daily as a thin layer on the affected area

Batrafen

Arm description

Reference product

Arm type

Active comparator

Investigational medicinal product name

Batrafen Cream 10 mg/g

Investigational medicinal product code

D01AE14

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

Application twice daily as a thin layer 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

Application twice daily as a thin layer on the affected area.

Number of subjects in period 1	Cic-C	Batrafen	Vehicle
Started	129	141	133
Completed	120	129	117
Not completed	9	12	16
Consent withdrawn by subject	1	-	1
Covid-related	1	2	2
Adverse event, non-fatal	1	1	-
Technical-logistic reasons	2	3	5
Poor tolerability	-	1	-
Lost to follow-up	3	4	3
Lack of efficacy	1	1	5

Baseline characteristics

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Reporting group title

Treatment Period

Reporting group description

Reporting group values	Treatment Period	Total
Number of subjects	403	403
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)	296	296
From 65-84 years	105	105
85 years and over	2	2
Gender categorical
Units: Subjects
Female	133	133
Male	270	270

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

FAS

Subject analysis set type

Full analysis

Subject analysis set description

Consists of all patients as randomised who received study medication at least once and have an assessment of the primary efficacy variable.

Subject analysis set title

Subject analysis set type

Per protocol

Subject analysis set description

Comprises all patients of the FAS who did not exhibit any major protocol violations.

Subject analysis sets values	Safety data set	FAS	PP
Number of subjects	394	390	370
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)	289	286	273
From 65-84 years	103	102	95
85 years and over	2	2	2
Age continuous
Units:
	( )	( )	( )
Gender categorical
Units: Subjects
Female	127	126	121
Male	267	264	249

End points

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Reporting group title

Cic-C

Reporting group description

Test product

Reporting group title

Batrafen

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

FAS

Subject analysis set type

Full analysis

Subject analysis set description

Consists of all patients as randomised who received study medication at least once and have an assessment of the primary efficacy variable.

Subject analysis set title

Subject analysis set type

Per protocol

Subject analysis set description

Comprises all patients of the FAS who did not exhibit any major protocol violations.

Primary: Clinical treatment success

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End point title

Clinical treatment success

End point description

The primary efficacy variable is clinical treatment success at the end-of-treatment examination at visit V4 (LOCF, i.e. last observation under treatment carried forward). Clinical treatment success was defined as ‘yes’ if the sum score of clinical parameters ≤ 2 AND all individual clinical score values ≤ 1 AND the mycological result was negative AND no further need for antimycotical treatment existed.

End point type

Primary

End point timeframe

Start of treatment (visit 1) to EOT (visit 4) with 3 weeks treatment.

End point values	Cic-C	Batrafen	Vehicle
Number of subjects analysed	119	129	131
Units: Percentage	45	66	46

Analysis of efficacy

Statistical analysis description

The primary objective of this study was to show therapeutic equivalence of the test preparation Cic-C compared to the approved reference Batrafen with respect to the primary efficacy variable. Therapeutic equivalence was statistically proven if the two-sided 95% confidence interval for πCic-C - πBatrafen was completely contained within [-20%, 20%].

Comparison groups

Batrafen v Cic-C

Number of subjects included in analysis

248

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

Mean difference (final values)

Point estimate

-13.35

Confidence interval

level

95%

sides

2-sided

lower limit

-26.42

upper limit

-0.28

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 (Fisher’s exact tests) with α = 5%. The primary test of superiority was carried out for the FAS data set.

Comparison groups

Cic-C v Vehicle

Number of subjects included in analysis

250

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6053

Method

Fisher exact

Confidence interval

Superiority of Reference over Vehicle

Statistical analysis description

Comparison groups

Batrafen v Vehicle

Number of subjects included in analysis

260

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0132

Method

Fisher exact

Confidence interval

Adverse events

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Timeframe for reporting adverse events

From the inclusion visit (V 1, day 0) to the final visit (V5, day 35, 2 weeks after EOT).

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

Cic-C

Reporting group description

Test product

Reporting group title

Batrafen

Reporting group description

Reference product

Reporting group title

Vehicle

Reporting group description

Vehicle of test product

Serious adverse events	Cic-C	Batrafen	Vehicle
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 126 (0.79%)	1 / 137 (0.73%)	1 / 131 (0.76%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Investigations
Weight decreased
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (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
Vascular disorders
Circulatory collapse
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (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
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 126 (0.00%)	1 / 137 (0.73%)	0 / 131 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	0 / 126 (0.00%)	0 / 137 (0.00%)	1 / 131 (0.76%)
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	Cic-C	Batrafen	Vehicle
Total subjects affected by non serious adverse events
subjects affected / exposed	18 / 126 (14.29%)	13 / 137 (9.49%)	20 / 131 (15.27%)
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
General disorders and administration site conditions
Application site dryness
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Application site erythema
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Application site pain
subjects affected / exposed	0 / 126 (0.00%)	2 / 137 (1.46%)	1 / 131 (0.76%)
occurrences all number	0	2	1
Application site paraesthesia
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Application site pruritus
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Feeling hot
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Peripheral swelling
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Swelling
subjects affected / exposed	0 / 126 (0.00%)	1 / 137 (0.73%)	0 / 131 (0.00%)
occurrences all number	0	1	0
Xerosis
subjects affected / exposed	0 / 126 (0.00%)	0 / 137 (0.00%)	1 / 131 (0.76%)
occurrences all number	0	0	1
Immune system disorders
Allergy to chemicals
subjects affected / exposed	0 / 126 (0.00%)	1 / 137 (0.73%)	0 / 131 (0.00%)
occurrences all number	0	1	0
Reproductive system and breast disorders
Menstrual disorder
subjects affected / exposed	0 / 126 (0.00%)	0 / 137 (0.00%)	1 / 131 (0.76%)
occurrences all number	0	0	1
Respiratory, thoracic and mediastinal disorders
Nasal polyps
subjects affected / exposed	0 / 126 (0.00%)	1 / 137 (0.73%)	0 / 131 (0.00%)
occurrences all number	0	1	0
Oropharyngeal pain
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	1 / 131 (0.76%)
occurrences all number	1	0	1
Psychiatric disorders
Depressed mood
subjects affected / exposed	0 / 126 (0.00%)	0 / 137 (0.00%)	1 / 131 (0.76%)
occurrences all number	0	0	1
Injury, poisoning and procedural complications
Skin laceration
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Nervous system disorders
Burning sensation
subjects affected / exposed	0 / 126 (0.00%)	1 / 137 (0.73%)	0 / 131 (0.00%)
occurrences all number	0	1	0
Headache
subjects affected / exposed	2 / 126 (1.59%)	1 / 137 (0.73%)	2 / 131 (1.53%)
occurrences all number	2	1	2
Paraesthesia
subjects affected / exposed	1 / 126 (0.79%)	2 / 137 (1.46%)	0 / 131 (0.00%)
occurrences all number	1	2	0
Eye disorders
Conjunctivitis allergic
subjects affected / exposed	0 / 126 (0.00%)	1 / 137 (0.73%)	0 / 131 (0.00%)
occurrences all number	0	1	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 126 (0.00%)	2 / 137 (1.46%)	0 / 131 (0.00%)
occurrences all number	0	2	0
Skin and subcutaneous tissue disorders
Dermatitis contact
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Dry skin
subjects affected / exposed	0 / 126 (0.00%)	0 / 137 (0.00%)	1 / 131 (0.76%)
occurrences all number	0	0	1
Eczema
subjects affected / exposed	2 / 126 (1.59%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	2	0	0
Erythema
subjects affected / exposed	1 / 126 (0.79%)	1 / 137 (0.73%)	0 / 131 (0.00%)
occurrences all number	1	1	0
Intertrigo
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Pruritus
subjects affected / exposed	0 / 126 (0.00%)	1 / 137 (0.73%)	0 / 131 (0.00%)
occurrences all number	0	1	0
Psoriasis
subjects affected / exposed	0 / 126 (0.00%)	0 / 137 (0.00%)	1 / 131 (0.76%)
occurrences all number	0	0	1
Rosacea
subjects affected / exposed	0 / 126 (0.00%)	0 / 137 (0.00%)	1 / 131 (0.76%)
occurrences all number	0	0	1
Skin exfoliation
subjects affected / exposed	0 / 126 (0.00%)	1 / 137 (0.73%)	0 / 131 (0.00%)
occurrences all number	0	1	0
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Musculoskeletal and connective tissue disorders
Arthritis
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Back pain
subjects affected / exposed	2 / 126 (1.59%)	2 / 137 (1.46%)	1 / 131 (0.76%)
occurrences all number	2	2	1
Infections and infestations
COVID-19
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Epididymitis
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Fungal infection
subjects affected / exposed	0 / 126 (0.00%)	0 / 137 (0.00%)	2 / 131 (1.53%)
occurrences all number	0	0	3
Fungal skin infection
subjects affected / exposed	0 / 126 (0.00%)	0 / 137 (0.00%)	1 / 131 (0.76%)
occurrences all number	0	0	2
Groin abscess
subjects affected / exposed	0 / 126 (0.00%)	0 / 137 (0.00%)	1 / 131 (0.76%)
occurrences all number	0	0	1
Nasopharyngitis
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	4 / 131 (3.05%)
occurrences all number	1	0	4
Pulpitis dental
subjects affected / exposed	0 / 126 (0.00%)	0 / 137 (0.00%)	1 / 131 (0.76%)
occurrences all number	0	0	1
Sinusitis
subjects affected / exposed	0 / 126 (0.00%)	1 / 137 (0.73%)	1 / 131 (0.76%)
occurrences all number	0	1	1
Tinea pedis
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0
Urinary tract infection
subjects affected / exposed	0 / 126 (0.00%)	1 / 137 (0.73%)	0 / 131 (0.00%)
occurrences all number	0	1	0
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	1 / 126 (0.79%)	0 / 137 (0.00%)	0 / 131 (0.00%)
occurrences all number	1	0	0

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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

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Clinical trials

Clinical Trial Results:
Double-blind, randomised clinical study comparing efficacy and safety of Ciclopirox Olamine Cream 10 mg/g (Test) vs. Batrafen® Cream (Reference) vs. Vehicle in patients with skin mycoses

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Clinical treatment success

Primary: Clinical treatment success

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: Double-blind, randomised clinical study comparing efficacy and safety of Ciclopirox Olamine Cream 10 mg/g (Test) vs. Batrafen® Cream (Reference) vs. Vehicle in patients with skin mycoses

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Clinical treatment success

Primary: Clinical treatment success

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 Ciclopirox Olamine Cream 10 mg/g (Test) vs. Batrafen® Cream (Reference) vs. Vehicle in patients with skin mycoses