Clinical Trials Register

Summary
EudraCT Number:	2012-002776-14
Sponsor's Protocol Code Number:	97
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:	2013-11-12
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

2012-002776-14

A.3

Full title of the trial

Ibuprofen versus mecillinam for uncomplicated cystitis in adult, non-pregnant women

Ibuprofen versus mecillinam til ukompliceret cystitis hos voksne, ikke-gravide kvinder

A.3.1

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

Treatment of cystitis in adult, non-pregnant women

Behandling af blærebetændelse hos voksne, ikke-gravide kvinder

A.3.2

Name or abbreviated title of the trial where available

Ibuprofen versus pivmecillinam til behandlingen af blærebætenselse

A.4.1

Sponsor's protocol code number

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	University of Oslo
B.1.3.4	Country	Norway
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	The Norwegian Research Council
B.4.2	Country	Norway
B.4.1	Name of organisation providing support	The National Centre of Emergency Primary Health Care
B.4.2	Country	Norway
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Afdeling for Almen medicin, Institut for folkesunhedsvidenskab, Københavns Universitet
B.5.2	Functional name of contact point	Lars Bjerrum
B.5.3	Address:
B.5.3.1	Street Address	Øster Farimagsgade 5,Opgang Q, stuen og 1.sal
B.5.3.2	Town/ city	København
B.5.3.3	Post code	1440
B.5.3.4	Country	Denmark
B.5.4	Telephone number	004535327960
B.5.6	E-mail	lbjerrum@sund.ku.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	Ibuprofen ratiopharm
D.2.1.1.2	Name of the Marketing Authorisation holder	Ratiopharm
D.2.1.2	Country which granted the Marketing Authorisation	Norway
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	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Gastroenteral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	64622-45-3
D.3.9.3	Other descriptive name	IBUPROFEN PICONOL
D.3.9.4	EV Substance Code	SUB14175MIG
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.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	Selexid
D.2.1.1.2	Name of the Marketing Authorisation holder	Leo Pharma
D.2.1.2	Country which granted the Marketing Authorisation	Norway
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	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Gastroenteral use
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.3.9.4	EV Substance Code	SUB09951MIG
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Uncomplicated cystitis in adult, non pregnant women, age 18-60.

Ukompliceret cystitis hos voksne, ikke gravide kvinder, alder 18-60.

E.1.1.1

Medical condition in easily understood language

Cystitis in women

blæreinfektion hos kvinder

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

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	10000699
E.1.2	Term	Acute cystitis (excl in pregnancy)
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

Uncomplicated cystitis is considered to be a mild condition and mostly self-limiting. Currently, the majority of patients are treated with antibiotics, which are known to give a quick relief of symptoms and shorten the course of the condition by a few days. The aim of this study is to evaluate ibuprofen versus mecillinam in the treatment of uncomplicated cystitis in otherwise healthy, non-pregnant women. Our main objective is to assess whether symptomatic treatment with ibuprofen is equally effective as the treatment with mecillinam.

Selv om ukompliceret cystitis er en mild tilstand og i mange tilfælde går over af sig selv, bliver størstedelen af patienterne behandlet med antibiotika. Formålet med denne undersøgelse er at evaluere ibuprofen versus mecillinam til behandlingen af ukompliceret cystitis hos voksne, ikke-gravide kvinder. Hovedformålet er at vurdere, om behandling med ibuprofen er lige så effektiv som behandling med mecillinam.

E.2.2

Secondary objectives of the trial

Are there more complications in the ibuprofen group compared to the mecillinam group? Are there more positive urine cultures in the ibuprofen group after two weeks?

Er der mere komplikationer i ibuprofen gruppen sammenlignet med mecillinam gruppen? Er der mere positiv urin kulturer i ibuprofen gruppen efter to uger?

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Women between 18 and 60 years of age. Dysuria and urinary frequency and/or urinary urgency. Ability to speak, understand and write Danish and ability to understand and sign the inform consent.

Kvinde mellem 18 og 60 år. Smerter ved vandladning. Hyppig vandladning og / eller vandladningstrang. Kan give skriftligt informeret samtykke.

E.4

Principal exclusion criteria

Pregnancy. Breastfeeding. Diabetes. kidney disease or use of the drug probenecid. Clinical suspicion of pyelonefritis: fever, reduced general condition, upper back pain. Vaginal symptoms such as discharge or irritation. Severe abdominal pain More than seven days with symptoms. One or more urinary tract infections within the lasts four weeks. Permanent bladder catheter or use of bladder catheter within the last four weeks. Use of antibiotics within the last two weeks. Previous allergic reaction to penicillin. Previous allergic reaction to ibuprofen, or worsening of asthma when taking NSAIDs. Narrow oesophagus. Severe gastritis or previous ulcer. Anticoagulative treatment. Ongoing use of steroids Use of immunosuppressant drugs. Thrombocytopenia Heart insufficiency. Severe psychiatric illness or dementia. Severe drug addiction. Unable to communicate in Norwegian, Swedish or Danish language.

Graviditet. Amning. Diabetes. Nyresygdom eller brug af medikamentet probenecid. Klinisk mistanke om øvre urinvejinfektion: feber, nedsat almentilstand, høje lændesmerter. Vaginale symptomer såsom udflåd eller irritation. Alvorlige mavesmerter symptomer. Mere end syv dage med symptomer. En eller flere urinvejsinfektioner i løbet af de sidste fire uger. Permanent blærekateter eller brug af blærekateter i løbet af de sidste fire uger. Brug af antibiotika i løbet af de sidste to uger. Tidligere allergisk reaktion over for penicillin, ibuprofen eller forværring af astma i forbindelse med brug af NSAID. Indsnævringer i spiserøret. Alvorlig gastritis eller tidligere mavesår. Antikoagulationsbehandling. Fast forbrug af steroider. Brug af immunosuppressive lægemidler. Trombocytopeni. Hjerteinsufficiens. Alvorlig psykiatrisk sygdom eller demens. Stofmisbrug. Kan ikke kommunikere på dansk.

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients who feel cured by day four as registered in the patient diary.

Andel af patienter som er uden symptomer fire dage efter start af behandling.

E.5.1.1

Timepoint(s) of evaluation of this end point

Four days

Fire dage

E.5.2

Secondary end point(s)

The patients’ symptom load with regard to dysuria, urinary frequency and/or urinary urgency. Proportion of patients who had a relapse of symptoms of uncomplicated cystitis within the study period. Proportion of patients who were in need of a secondary medical consultation within the study period. Proportion of patients who developed an upper urinary tract infection (pyelonefritis). Proportion of patients who experienced severe adverse effects. Proportion of patients with a positive urine culture after two weeks.

Patienters symptom belastningen med hensyn til smerter ved vandladning, hyppig vandladning og /eller vandladningstrang. Andel af patienter, der fik tilbagefald af symptomer på cystitis i løbet af studieperioden. Andel af patienter, der havde brug for en ny konsultation i løbet af studieperioden. Andel af patienter, som udviklede en øvre urinvejsinfektion (pyelonefritis). Andel af patienter, som oplevede alvorlige bivirkninger. Andel af patienter med en positiv urin dyrkning efter to uger.

E.5.2.1

Timepoint(s) of evaluation of this end point

Two weeks

To uger

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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

We will end the trial when a sufficient number of patients have been included according to the power calculation, i.e. 400 patients in total, 200 in Oslo and 70 at each of the other three study sites. End of trial is two weeks after the visit of the last subject undergoing the trial since the follow up of the subject is two weeks after inclusion in the trial.

Inkludering af nye patienter afsluttes, når der er inkluderet 400 pateinter, heraf 70 fra Danmark. Forsøget afsluttes 2 uger efter inklusionen af den sidste patient idet opfølgningen varer 2 uger.

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

E.8.9.2

In all countries concerned by the trial 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:

400

F.1.3

Elderly (>=65 years)

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 2013-11-12.

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

400

F.4.2.2

In the whole clinical trial

400

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

Ingen

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	EMA Oslo
G.4.3.4	Network Country	Norway
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	EMA Bergen
G.4.3.4	Network Country	Norway
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	University of Copenhagen, Dept of General Practice
G.4.3.4	Network Country	Denmark
G.4 Investigator Network to be involved in the Trial: 4
G.4.1	Name of Organisation	University of Lund, Dept of General Practice
G.4.3.4	Network Country	Sweden

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-11-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-10-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-04-30

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