Clinical Trials Register

Summary
EudraCT Number:	2019-003541-15
Sponsor's Protocol Code Number:	2019-Fungi
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-12-20
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2019-003541-15

A.3

Full title of the trial

Adjunct effect of fluconazole in the treatment of Candida-associated refractory severe periodontitis – A single-center, placebo-controlled, triple blind, randomized clinical trial

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Supplementary effect of antimycotics in the treatment of destructive gum disease – A placebo-controlled, blind, randomized clinical trial

A.3.2

Name or abbreviated title of the trial where available

Candida and periodontitis

A.4.1

Sponsor's protocol code number

2019-Fungi

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Aarhus University
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Independent Research Fund Denmark
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Aarhus University
B.5.2	Functional name of contact point	Section of Periodontology
B.5.3	Address:
B.5.3.1	Street Address	Vennelyst Boulevard 9
B.5.3.2	Town/ city	Aarhus C
B.5.3.3	Post code	DK-8000
B.5.3.4	Country	Denmark
B.5.6	E-mail	rlopez@dent.au.dk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Fluconazol "Krka"
D.2.1.1.2	Name of the Marketing Authorisation holder	Krka Sverige AB
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Fluconazol Krka
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FLUCONAZOLE
D.3.9.1	CAS number	86386-73-4
D.3.9.3	Other descriptive name	FLUCONAZOLE
D.3.9.4	EV Substance Code	SUB07674MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Periodontitis.

The participants are in good general health, but have at least 2 residual dental lesions after periodontal treatment (standard care).

E.1.1.1

Medical condition in easily understood language

Gum disease

E.1.1.2

Therapeutic area

Diseases [C] - Mouth and tooth diseases [C07]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10009102
E.1.2	Term	Chronic periodontitis
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1) To investigate the effect of systemic fluconazole as adjunctive to standard care (professional mechanical biofilm control) on Candida-associated refractory periodontitis lesions. Treatment success is defined as absence of periodontal probing depth ≥ 5 mm and bleeding on probing at 3 months after treatment of sites presenting refractory periodontitis lesions at baseline.

E.2.2

Secondary objectives of the trial

1) Maintain the stability of clinical attachment levels obtained at 3 months. Defined as absence of sites losing more than 1 mm of clinical attachment level in total after 12, 24 and 36 months after completion of the intervention.
2) To determine the susceptibility to fluconazole in the identified Candida isolates before treatment and after 3 months of the intervention.
3) To describe the occurrence of Candida and distribution of Candida species in refractory periodontitis lesions.
4) To reduce significantly the total number of Candida and/or proportions of Candida of the total cultivable microbiota after 3 months of the intervention, and maintain the achieved levels of Candida at the 12- and 24-month follow-up appointments.
5) To adapt a real-time PCR method validated for blood samples for the detection of Candida species in periodontitis lesions and compare PCR with standard cultivation.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Volunteers aged 20-70 yr.
• At least 15 teeth
• At least two periodontitis lesions presenting with ≥ 3 mm loss of clinical attachment level, ≥ 5 mm of probing depth, and bleeding on probing
• Antibiotics prescribed from dentist within the last 12 months
• Fertile women: use of safe contraceptive measures (defined as intrauterine devices or hormonal contraception: oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections)

E.4

Principal exclusion criteria

• Presence of dental calculus that reveals poorly treated/untreated periodontitis;
• Need for antibiotic prophylaxis before mechanical biofilm control;
• Allergy to antimycotics;
• Use of medication precluding the use of fluconazole:
1. Amiodaron
2. Fluvastatin
3. Pimozide
4. Rifampicin (only if long duration of treatment)
5. Erythromycin (only if long duration of treatment)
• Systemic conditions precluding the use of fluconazole:
1. reduced adrenocortical function
2. galactose intolerance
3. complete lactase deficiency
4. glucose/galactose malabsorption
5. hypo serum potassium
6. advanced heart failure
7. proarythmic conditions
• Allergy to other components of fluconazol ”Krka”.
• Fertile women using safe contraceptive measures: current pregnancy (will be assessed with urine pregnancy test)
• Fertile women using safe contraceptive measures: current breastfeeding
• For menopausal women: Duration of menopause for less than 12 months

E.5 End points

E.5.1

Primary end point(s)

No sites with bleeding on probing (BOP) and probing depth (PD) ≥ 5 mm at 3 months, in refractory periodontitis lesions identified at the initial clinical exam.

E.5.1.1

Timepoint(s) of evaluation of this end point

1) 3 months after the intervention

E.5.2

Secondary end point(s)

1) No sites presenting loss of clinical attachment level ≥ 1 mm at the 12-, 24- and 36-month follow-up appointments.
2) No change in susceptibility levels to fluconazole in Candida isolates from the initial clinical exam to 3 months after intervention.
3) No endpoint for secondary objective 3 because it is descriptive.
4) No endpoint for secondary objective 4 because there are not data available to present a realistic estimate. Elimination of Candida cannot be expected since it is a resident of the oral microbiota in up to 50% of the healthy population.
5) No endpoint for secondary objective 5 because it is a methodological evaluation.

E.5.2.1

Timepoint(s) of evaluation of this end point

1) 12-, 24-, and 36- months after the intervention
2) 3 months after the intervention
3) baseline
4) 3-, 12-, and 24- months after the intervention
5) baseline, 3-, 12-, and 24- months after the intervention

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Methodological validation of PCR technique

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

triple blind (data analyst will be blind)

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

none

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-02-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-02-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-11-19

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

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