Clinical Trials Register

Summary
EudraCT Number:	2014-001321-32
Sponsor's Protocol Code Number:	198809
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-04-14
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

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A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2014-001321-32

A.3

Full title of the trial

The efficacy of pivmecillinam 3 days respectively 5 days t.i.d against community acquired uncomplicated urinary tract infections

A.3.1

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

The efficacy of pivmecillinam 3 days respectively 5 days three times daily against community acquired uncomplicated urinary tract infections

A.4.1

Sponsor's protocol code number

198809

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	Department of Clinical Microbiology, Hvidovre Hospital
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	Department of Clinical Microbiology, Hvidovre Hospital, 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	Department of Clinical Microbiology, Hvidovre Hospital
B.5.2	Functional name of contact point	Department of Clinical Microbiology
B.5.3	Address:
B.5.3.1	Street Address	Kettegård Allé 30
B.5.3.2	Town/ city	Hvidovre
B.5.3.3	Post code	2650
B.5.3.4	Country	Denmark
B.5.4	Telephone number	004536322428
B.5.6	E-mail	Inge.Jenny.Dahl.Knudsen@regionh.dk

D. IMP Identification
D.IMP: 1
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	Selexid 400 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	LEO Pharma
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.3.4	Pharmaceutical form	Coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PIVMECILLINAM
D.3.9.1	CAS number	32886-97-8
D.3.9.3	Other descriptive name	pivmecillinamhydrochlorid
D.3.9.4	EV Substance Code	SUB09951MIG
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	400
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Lower Uncomplicated Urinary Tract Infection

E.1.1.1

Medical condition in easily understood language

Lower Uncomplicated Urinary Tract Infection

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	17.1
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

Identify and compare the efficacy of pivmecillinam 400 mg t.i.d in a 3-day respectively 5-day regimen, against community acquired lower urinary tract infections i.e. in women at the age of 18-70 years old.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Women in the age of 18-70 years old, with clinical features of community acquired uncomplicated UTI and ability to understand the study and give written consent. Patients should have a symptom cumulative score of ≥ 2 p (i.e. none, mild, moderate or severe, scoring 0-3, respectively) in accordance to the validated questionnaires for uncomplicated UTI. The following signs and symptoms are included:
• Dysuria (i.e. pain or burning sensation on urination)
• Urgency (i.e. feeling an increased and more frequent need to urinate)
• Pollakisuria/frequency (i.e. urinating more frequently than usually)
An accepted definition of uncomplicated urinary tract infections is symptoms in concordance with uUTI and significant bacteriuria of uropathogenic bacteria1, but we have chosen not include the latter criteria in our ITT analysis. This is because we want the included patients in the ITT group to mimic the realistic settings as much as possible (i.e. in which patients with uUTI will receive antibiotic therapy without urine samples in most primary care settings).

E.4

Principal exclusion criteria

Absolute exclusion criteria are:

• Clear signs of pyelonephritis (high fever ≥38,5°C or back/flank pain), or high suspicion of pyelonephritis
• Allergy to penicillins
Symptom related exclusion criteria:
• Clear vaginal symptoms, i.e. discharge and/or pain
Any condition that may lead or predispose to complicated urinary infection:
• Indwelling urinary catheter
• Pregnancy
• Immunosuppressive therapy
• Abnormal/pathological urinary tracts (e.g. renal disease, known presence of urinary stones, past urinary interventions/surgery, genetic aciduria)
• Hard treated recurrent UTIs
• Serious neurological disease affecting the bladder (i.e. paraplegia, multiple sclerosis, epilepsy)
Other complicating or contradictive conditions:
• Ongoing breastfeeding
• Ongoing/current antibiotic therapy
• Oesophageal stricture
• Current intake of allopurinol (i.e. increases the risk of allergic skin reaction to mecillinam) or probenecid (i.e. decrease the renal excretion of mecillinam)
• Currently part of another clinical trail
• Unwilling to participate in study (i.e. not wanting to sign consent form)
• Inability/unable to understand and/or take part in the clinical trial
• Incapable of following the instructions of the study
There are no known drugs beside those listed in the exclusion criteria to have significant interaction with mecillinam. Thus, all other drugs (prescribed or non-prescription) should be taken as usual throughout the study (which will be explained by the GP). However, all drugs should be registered in the diary and/or given permission by the patient for us to look it up on the national database of medicine prescriptions.

E.5 End points

E.5.1

Primary end point(s)

We have 2 co-primary endpoints
Co-primary endpoint no. 1 – initial clinical cure (i.e. what group experience clinical cure fastest).
Co-primary endpoint no. 2 – initial bacteriological cure rate (i.e. control urine sample no. 1 compared to pre-treatment urine sample).

E.5.1.1

Timepoint(s) of evaluation of this end point

Both primary endpoints will be evaluated at the intervene analysis (i.e. the first 300 included patients to see if there is a large difference that will make it unethical for us to proceed with the study), and finally at the end of the trail (i.e. after the last patient is included

E.5.2

Secondary end point(s)

1. Clinical signs and symptoms in uncomplicated urinary tract infections in women.
2. Frequency and timing of relapse of symptoms and/or bacteriuria.
3. Bacteriological findings (i.e. ESBL producing bacteria)
4. Complications (i.e. urosepsis and/or pyelonephritis)

E.5.2.1

Timepoint(s) of evaluation of this end point

All secondary endpoints will be evaluated at the intervene analysis (i.e. the first 300 included patients to see if there is a large difference that will make it unethical for us to proceed with the study), and finally at the end of the trail (i.e. after the last patient is included

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

E.6.4

Safety

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)

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

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

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

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

Yes

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:

425

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

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2015-04-14.

Yes

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

500

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)

Patients are told at recruitment to visit the GP again if she would keep having ongoing or even develop worsening of symptoms during the study period, just as she normally would do. In that case the GP would be able to choose a new treatment strategy for the patient and will have the potential microbiological diagnostic answers (i.e. from pre-treatment urine sample) to take in consideration in this approach.

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

2015-04-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-08-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-12-22

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