Clinical Trials Register

Summary
EudraCT Number:	2009-015864-32
Sponsor's Protocol Code Number:	DORIPED3001
National Competent Authority:	Latvia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-11-24
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

Latvia - SAM

A.2

EudraCT number

2009-015864-32

A.3

Full title of the trial

A Prospective, Randomized, Double-Blind, Multicenter Study to Establish the Safety and Tolerability of Doripenem Compared With Meropenem in Hospitalized Children With Complicated Intra-Abdominal Infections

A.3.1

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

A Safety and Tolerability Study of Doripenem Compared with Meropenem in Children Hospitalized with Complicated Intra-abdominal Infections

A.4.1

Sponsor's protocol code number

DORIPED3001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01110382

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/192/2010

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Janssen-Cilag International NV, Turnhoutseweg 30, 2340 Beerse, Belgium
B.1.3.4	Country	Belgium
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	Johnson & Johnson Pharmaceutical Research & Development
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen- Cilag International NV
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Janssen Biologics BV - Clinical Registry Group - Archimedesweg 29
B.5.3.2	Town/ city	2333CM
B.5.3.3	Post code	Leiden
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31715242166
B.5.5	Fax number	+31715242110
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.com

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	DORIBAX
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DORIPENEM MONOHYDRATE
D.3.9.1	CAS number	364622-82-2
D.3.9.2	Current sponsor code	JNJ-38174942
D.3.9.3	Other descriptive name	DORIPENEM
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	500
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	MERONEM
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca 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	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MEROPENEM
D.3.9.1	CAS number	96036-03-2
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	1
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: 3
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.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MEROPENEM
D.3.9.1	CAS number	96036-03-2
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	1
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	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous bolus use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Complicated Intra-Abdominal Infections

E.1.1.1

Medical condition in easily understood language

Abscess, Intra-Abdominal;
Abdominal Abscess;
Abdomen, Acute;
Abdominal Pain;
Appendicitis;
Rupture;
Infection;
Intestinal Perforation;
Peritonitis;
Ileus.

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	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10056570
E.1.2	Term	Intra-abdominal infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to establish the safety and tolerability profile of doripenem compared with that of meropenem in hospitalized children 3 months to <18 years of age with cIAI (complicated intra-abdominal infection).

E.2.2

Secondary objectives of the trial

The secondary objectives are:
•To determine the clinical cure rate of doripenem compared with that of meropenem at the TOC (test of cure) visit
•To determine the favorable microbiological response rate of doripenem compared with that of meropenem at the TOC visit
•To determine the clinical improvement rate of doripenem compared with that of meropenem at the end-of-treatment for IV study drug therapy (EIV) visit
•To determine the clinical cure rate of doripenem compared with that of meropenem at the late follow-up (LFU) visit
•To determine the favorable microbiological response rate of doripenem compared with that of meropenem at the LFU visit
•To characterize the pharmacokinetics of doripenem in hospitalized children with cIAI based on a sparse pharmacokinetic sampling scheme

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 - Subject randomly assigned to treatment postoperatively or intra-operatively after visual confirmation of established cIAI (presence of pus within the abdominal cavity) including the following eligible diagnoses:
– appendicitis complicated by rupture and/or abscess
– traumatic perforation of the intestines, which are being operated on more than 12 hours after perforation occurred
– acute gastric, duodenal, or gall bladder perforations, which are being operated on more than 24 hours after perforation occurred
– secondary peritonitis due to perforated viscus, postoperative or other focus of infection. (Subjects with inflammatory bowel disease or ischemic bowel disease are eligible to enroll provided there is bowel perforation)
– intra-abdominal bacterial abscess (including liver)
OR
Subject randomly assigned to treatment pre-operatively and has pre-operative clinical evidence of cIAI including all of the following:
– Evidence of systemic inflammatory response as demonstrated by at least one of the following:
 Fever (oral temperature >38.0C, tympanic temperature >38.3C, or rectal or core temperature >38.8C) or hypothermia (rectal or core temperature <35.0C)
 Have leukocytosis (WBC count ≥15,000 cells/µL OR ≥15% immature neutrophils , regardless of the total peripheral white cell count)
 Hypotension defined by the following:
o For children greater than 1 year of age: Systolic blood pressure ≤70 mm Hg + (2 multiplied by age [in years])
o For children aged 3 months to ≤1 year: Systolic blood pressure ≤70 mm Hg
AND
– At least one of the following physical signs consistent with cIAI:
o Abdominal pain or tenderness
o Localized or diffused abdominal wall rigidity
o Presence of abdominal mass
o Ileus
AND
– Supportive radiologic findings in the abdomen such as intraperitoneal abscess detected on computer tomography scan films or an ultrasound;
2 - Must have a requirement for surgical intervention (eg, laparotomy, laparoscopic surgery, or percutaneous drainage) to manage the cIAI within the 24 hours before to within the 24 hours after randomization;
3 - Must, based on the judgment of the investigator, require hospitalization initially and antibacterial therapy for 5 to 14 days in addition to surgical intervention for the treatment of the current cIAI. (Note that the subject must require at least 3 days of IV antibiotic therapy initially).

E.4

Principal exclusion criteria

1 - Have a history of hypersensitivity reactions to carbapenems, cephalosporins, penicillins, or other β-lactam antibiotics. Note: Subjects with a history of mild non urticarial skin rash temporally related to but considered not associated with the previous use of β-lactam antibiotics are permitted to enroll in the study. For such subjects, there must be a description of the rash and documentation by the investigator that upon review of the history it is his/her opinion that the rash was unlikely due to any of the above-mentioned classes of drugs for the subject to qualify for inclusion in the study;
2 - Concomitant infection including but not limited to suspected or confirmed meningitis or other CNS infection requiring systemic antibiotic or antifungal therapy at the time of randomization. (Clarification: possible bacteremia with a presumed intra abdominal pathogen is acceptable);
3 - Have received more than 24 hours of systemic antibiotic therapy immediately preceding the start of the infusion of the first dose of IV study drug therapy
4 - Girls who are pregnant or are nursing a child or are menarchal, and if sexually active are not practicing a highly effective method of birth control (eg, prescription hormonal contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method, eg, condoms, diaphragm, or cervical cap, with spermicidal foam, cream or gel, male partner sterilization) as local regulations permit, before screening and do not agree to continue using a highly effective method of birth control (as previously described) for 30 days after administration of the last dose of study drug therapy. Note: for all menarchal girls, confirm a negative urine or serum pregnancy test (β-human chorionic gonadotropin [β-hCG]) at screening, before enrolling the subject into the study;
5 - Have a history of uncontrolled epilepsy defined as at least 1 seizure within the 6 months before randomization.

E.5 End points

E.5.1

Primary end point(s)

The safety of doripenem compared with meropenem in children with cIAI will be evaluated by monitoring adverse events, changes in clinical laboratory tests, and findings from vital signs measurements and physical examinations.

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety will be assessed during the 5 to 14 day treatment period and at posttreatment visits scheduled 7 to 14 days and 28 to 42 days, respectively, after the last dose of study drug.

E.5.2

Secondary end point(s)

1 - Clinical cure rate and favorable per-patient microbiological response rate of doripenem compared with meropenem at test of cure (TOC) visit
2 - Clinical improvement of doripenem compared with meropenem at end of treatment (EIV) for iv study drug therapy
3 - Clinical cure rate and favorable per-patient microbiological response rate of doripenem compared with meropenem at late follow Up (LFU) visit
4 - Characterize pharmacokinetics of doripenem in hospitalized children with cIAI on the basis of a sparse pharmacokinetic sampling scheme

E.5.2.1

Timepoint(s) of evaluation of this end point

1 - 7 to 14 days after the last dose of study drug
2 - Within 24 hours after completion of the last dose of iv study drug
3 - 28 to 42 days after the last dose of study drug
4 - 1, 2, 4 and 6 hours after the 4th, 5th, 6th, or 7th dose administrations of doripenem/doripenem placebo

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

E.6.6

Pharmacokinetic

Yes

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

Tolerability

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

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

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

Argentina

Brazil

Colombia

India

Latvia

Lithuania

Panama

United States

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

End of trial is last visit of the last subject (Late Follow Up visit (LFU)

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

Yes

F.1.1

Number of subjects for this age range:

140

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

pediatric popultion: subjects from 3 months to <18 years of age

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

F.4.2.2

In the whole clinical trial

140

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)

After the study is over, the sponsor will not continue to provide the subject with the study medication. The subjects will be followed by the study doctor according to the local standard of care.

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

2011-01-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-12-16

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2013-08-05

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