Clinical Trials Register

Summary
EudraCT Number:	2013-004529-99
Sponsor's Protocol Code Number:	CanUTI-7
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-08-17
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

Germany - BfArM

A.2

EudraCT number

2013-004529-99

A.3

Full title of the trial

A double-blind, controlled, parallel-group, randomized, multicenter clinical trial to assess the efficacy and safety of a herbal drug containing centaury, lovage root, and rosemary leaf (CLR) in comparison to fosfomycin trometamol for the treatment of acute lower uncomplicated urinary tract infections (uUTIs) in women

A.3.1

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

Efficacy of a herbal drug called “CLR” compared to the antibiotic “fosfomycin trometamol” in acute lower urinary tract infections

A.4.1

Sponsor's protocol code number

CanUTI-7

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	Bionorica SE
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bionorica SE
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bionorica SE
B.5.2	Functional name of contact point	Clinical Research Department
B.5.3	Address:
B.5.3.1	Street Address	Kerschensteinerstraße 11-15
B.5.3.2	Town/ city	Neumarkt
B.5.3.3	Post code	92318
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49 9181231 114
B.5.5	Fax number	+49 9181231 6114
B.5.6	E-mail	canuti7@bionorica.de

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	Canephron® N
D.2.1.1.2	Name of the Marketing Authorisation holder	BIONORICA SE
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	Pharmaceutical form	Coated tablet
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	ROSEMARY LEAF, pulv.
D.3.9.3	Other descriptive name	ROSEMARY LEAF
D.3.9.4	EV Substance Code	SUB12261MIG
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	18
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LOVAGE ROOT, pulv.
D.3.9.3	Other descriptive name	LOVAGE ROOT
D.3.9.4	EV Substance Code	SUB12112MIG
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	18
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Centaury, pulv.
D.3.9.3	Other descriptive name	Centaury, pulv.
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	18
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Monuril 3000 mg granules
D.2.1.1.2	Name of the Marketing Authorisation holder	Zambon GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	Pharmaceutical form	Granules
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	FOSFOMYCIN TROMETAMOL
D.3.9.1	CAS number	78964-85-9
D.3.9.4	EV Substance Code	SUB02263MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5.631
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	Coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Granules
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

Acute lower uncomplicated urinary tract infection

E.1.1.1

Medical condition in easily understood language

Acute uncomplicated infection of the lower urinary tract

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10024981
E.1.2	Term	Lower urinary tract infection
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

To demonstrate non-inferiority of a non-antibiotic therapy with CLR versus an antibiotic treatment with fosfomycin trometamol in women suffering from acute lower uUTIs as measured by the proportion of patients who received an additional antibiotic treatment for acute lower uUTIs during the trial.

E.2.2

Secondary objectives of the trial

The secondary objective of this trial is to provide further efficacy data supporting the primary efficacy analysis and assess safety and tolerability of CLR for the treatment of acute lower uUTIs.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent (IC) and data protection declaration.
2. Female outpatients aged 18 to 70 years.
3. Sum-score of the three main uUTI symptoms (dysuria [“feeling pain or burning when passing urine”, No.3], pollakisuria [“frequent urination of small volumes of urine”, No. 1], and urgency [“Urgent urination”, No. 2]) reported on the ACSS-”Typical” domain at Visit 1 is ≥6.
4. Symptoms of the acute episode of lower uUTI are developed within not more than 6 days prior to Visit 1.
5. Leukocyturia at Visit 1, confirmed by positive dipstick
6. Patients willing to refrain from consuming prohibited concomitant medications and products
7. Non-lactating female patients who are surgically sterile (have had a documented sterilization, bilateral oophorectomy at least 3 months before the start of the trial and/or hysterectomy), or postmenopausal (cessation of menses for at least 12 months), or women of childbearing potential with a negative pregnancy test at Visit 1 willing to use highly effective (failure rate less than 1% per year, i.e., Pearl Index <1) contraception methods, e.g., contraceptive patch, oral, injected or implanted hormonal methods of contraception, during the trial including the follow-up period.

E.4

Principal exclusion criteria

1. Any signs of complicated UTIs, pyelonephritis (i.e., fever T ≥38.0°C [grade 2], flank and/or back pain, chills and shivers), and/or vulvo-vaginitis with vaginal and/or with urethral discharge (without urination) at Visit 1.
2. Any conditions that may lead to complicated infections (i.e., renal diseases, urinary tract abnormalities or past urinary surgery, urine catheterization, uncontrolled diabetes mellitus, spinal cord injury, etc.).
3. Chronic infection of the urinary tract known from medical history.
4. Persisting signs or symptoms of severe, progressive, or uncontrolled systemic disease (i.e., renal, hepatic, biliary, hematological, gastro-intestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease).
5. Uncontrolled hypertension (a diastolic blood pressure >95 mmHg at Visit 1).
6. Known severe cardiac insufficiency, coronary heart disease, valvular heart disease, cardiac arrhythmia, QT interval prolongation or other severe cardiac disease at Visit 1.
7. Any antibiotic therapy within 30 days prior to Visit 1.
8. Other acute infections (except uUTIs) requiring antibiotic treatment at Visit 1.
9. Patients receiving treatment for suspected or confirmed UTI (antibiotic or phytopharmaceutical) within 30 days prior to Visit 1.
10. Patients who took anti-inflammatory or analgesic drugs (e.g. ibuprofen, paracetamol, acetylsalicylic acid) or spasmolytics for any reason within 24 hours prior to Visit 1, and/or are not willing to stop the intake of any of the following medication not permitted for use during the trial: Rosmarini folium, Levistici radix, and Centaurii herba supplements other than the CLR (IMP), anti-inflammatory or analgesic drugs (e.g. ibuprofen, acetylsalicylic acid, with exception of paracetamol), spasmolytics, herbal drugs or supplements, cranberry juice, and kidney or bladder teas.
11. Known severe impaired renal function (creatinine clearance <20 mL/min).
13. Active peptic ulcers.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the intake of any additional antibiotic medication for acute lower uUTIs between Visit 1 and Visit 4.

E.5.1.1

Timepoint(s) of evaluation of this end point

See E.5.1

E.5.2

Secondary end point(s)

1. Intake of an antibiotic treatment for acute lower uUTI in addition to the trial treatment by reason of persistent symptoms (assessed by investigator) between Visit 1 and Visit 4.
2. Intake of an antibiotic treatment for acute lower uUTI in addition to the trial treatment by reason of recurrent symptoms (assessed by investigator) between Visit 1 and Visit 4.
3. Efficacy endpoints based on ACSS questionnaire assessments at Visit 2, Visit 3 and Visit 4, including:
o Severity of each uUTI symptom reported on the ACSS-”Typical” domain
o Sum-score of the ACSS-”Typical” domain
o Sum-score of the main uUTI symptoms (dysuria, pollakisuria, and urgency) reported on the ACSS-”Typical” domain
o Clearance of the uUTI symptoms reported on the ACSS-”Typical” domain (clearance is observed when none of the uUTI symptoms is >1)
o Clinical change (clinical cure, improved, clinical failure)
o Clinical cure = Sum-score of the main uUTI symptoms (dysuria, pollakisuria, and urgency) reported on the ACSS-”Typical” domain is ≤3 and none of the symptoms is >1
o Clinical failure = Sum-score of the main uUTI symptoms (dysuria,
pollakisuria, and urgency) reported on the ACSS-”Typical” domain is ≥6
o Improved = Patients which meet neither the criteria of clinical cure nor the criteria of clinical failure
o ACSS-”Dynamics” domain score
o Single-item scores of the ACSS-”Quality of life” domain
o Sum-score of the ACSS-”Quality of life” domain
4. Amount of bacteriuria (in CFU/mL) at Visit 3 and Visit 4.
5. Significant bacteriuria (≥103 CFU/mL), non significant bacteriuria, and unknown bacteriuria (meaning that microbiological tests were not available for a certain reason, e.g. too small urine sample) at Visit 1, Visit 3 and Visit 4.
6. Leukocyturia (positive dipstick) at Visit 3 and Visit 4.
7. Paracetamol intake for acute lower uUTI symptoms from Visit 1 to Visit 4.
8. Investigator’s and patient’s overall assessment of efficacy at Visit 3 and Visit 4.
9. Interleukins (e.g. IL-6, IL-8), prostaglandins (e.g. PGE2), and creatinine levels (for normalization) in urine collected at Visit 1 and Visit 3 in a subset of patients in selected investigational sites (centers).

The following safety endpoints will be evaluated in this trial:
10. Treatment-emergent adverse events (TEAEs), related TEAEs, and serious adverse events (SAEs).
11. Safety laboratory parameters (blood and urine) at Visit 3 and Visit 4.
12. Investigator’s and patient’s overall assessments of tolerability at Visit 3 and Visit 4.
13. Physical examination at Visit 1, Visit 3 and Visit 4.
14. Vital signs at Visit 1, Visit 3 and Visit 4.

E.5.2.1

Timepoint(s) of evaluation of this end point

See E.5.2

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

Yes

E.6.5

Efficacy

Yes

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

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Ukraine

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

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:

483

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

161

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

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

214

F.4.2

For a multinational trial

F.4.2.1

In the EEA

429

F.4.2.2

In the whole clinical trial

644

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)

The following treatment options exist in case patients terminate clinical trial participation prematurely:
- Patients can purchase Canephron N in the pharmacy over the counter
- Patients can receive standard therapy according to the clinical routine, at the discretion of the investigator/physician.
Generally, uUTI is an acute indication. Normally, it is cured within regular duration of the clinical trial. Persistent and recurrent symptoms, resp., will be treated according to clinical routine.

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

2015-10-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-17

P. End of Trial
P.	End of Trial Status	Completed

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