Clinical Trials Register

Summary
EudraCT Number:	2006-004291-12
Sponsor's Protocol Code Number:	101.1.C.004
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-01-07
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2006-004291-12

A.3

Full title of the trial

'' A multi-national, multi-centre, double-blind,randomised, parallel group study to compare the safety and efficacy of 200mg PAR-101 taken q12h with 125mg Vancomycin taken q6h for ten days in subjects with Clostridium Difficile-associated Diarrhea''

`` A multi-national, multi-centre, double-blind,randomised, parallel group study to compare the safety and efficacy of 200mg PAR-101 taken q12h with 125mg Vancomycin taken q6h for ten days in subjects with Clostridium Difficile-associated Diarrhea``

A.3.2

Name or abbreviated title of the trial where available

A double-blind, randomized study of PAR-101vs vancomycin in CDAD

Studio randomizzato in doppio cieco di PAR-101

A.4.1

Sponsor's protocol code number

101.1.C.004

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	OPTIMER PHARMACEUTICALS INC
B.1.3.4	Country	United States
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	No
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	PAR-101/OPT-80
D.3.2	Product code	PAR-101/OPT-80
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	Fidaxomicin
D.3.9.1	CAS number	873857-62-6
D.3.9.2	Current sponsor code	PAR-101/OPT-80
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	200
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	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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile
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	Vancocin
D.2.1.1.2	Name of the Marketing Authorisation holder	ViroPharma (US)
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	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	Vancomycin
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	125
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	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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile

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, hard
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

Patients 16 years old or older who have CDAD as defined by: -Diarrhoea:is defined as a change in bowel habits, with >3 unformed bowel movements in the 24 hours prior to randomization, -Presence of either toxin A or B of C.Difficile in the stool within 48 hours of randomization (for metronidazole failures) or 96 hours of randomization (for subjects with ≤ 24 hours pretreatment with C. difficile therapy).

Soggetti di entrambi i sessi, di eta` pari o superiore a 16 anni, con diagnosi di CDAD. Diarrea: definita come una variazione nell`attivita` intestinale abituale, con > 3 evacuazioni intestinali con feci non formate nella 24 ore precedenti la randomizzazione,e Presenza della tossina A o B di C. difficile nelle feci Presenza della tossina A o B di C. difficile nelle feci nelle 48 ore precedenti la randomizzazione (per i falliti al metronidazolo) o nelle 96 ore (per soggetti con <= 24 ore di

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10012742
E.1.2	Term	Diarrhoea infectious
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

Demonstrate that the cure rate of CDAD following treatment with PAR-101/OPT-80 is no worse than that following treatment with vancomycin. Evaluate the safety and tolerability of PAR-101/OPT-80 in subjects with CDAD.

Dimostrare che il tasso di guarigione della CDAD dopo trattamento con PAR-101/OPT-80 non e' inferiore a quello dopo trattamento con vancomicina. Valutare la sicurezza e la tollerabilita' di PAR-101/OPT-80 in soggetti con CDAD

E.2.2

Secondary objectives of the trial

Demonstrate that the rate of recurrence of CDAD following treatment with PAR-101/OPT 80 is no worse than that following treatment with vancomycin.

Dimostrare che il tasso di ricorrenza di CDAD dopo trattamento con PAR-101/OPT-80 non e' inferiore a quello dopo trattamento con vancomicina.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female in/outpatients 16 years old or older who have CDAD as defined by: -Diarrhoea:is defined as a change in bowel habits, with >3 unformed bowel movements in the 24 hours prior to randomization, -Presence of either toxin A or B of C.Difficile in the stool within 48 hours of randomization (for metronidazole failures) or 96 hours of randomization (for subjects with ≤ 24 hours pretreatment with C. difficile therapy). 2. Femalesubjects of childbearing potential must be using an adequate and reliable method of contraception (eg. barrier with additional spermicide foam or jelly, intrauterine device, hormonal contraception). females who are postmenopausal must have been postmenopausal at least 1 year. Subjects (both male and female)must agree to avoid contraception during treatment and for four weeks following the end of study treatments. 3. All subjects will be required to sign an Informed Consent form. 4. Opiates will be permitted as long as the subjects is on a stable dose at the time of randomization and is expected to mantein this dose during the treatment period: PRN opiate is permitted as long as the total daily dose is not changed during the treatment period. 5. Subjects who have failed at least a full 3-day course of metronidazole but continue to meet the definition of diarrhea without any significant clinical emprovement and remain toxin positive maybe enrolled in the study.

1. Soggetti di entrambi i sessi, di eta` pari o superiore a 16 anni, con diagnosi di CDAD definita come:¿ Diarrea:una variazione nell`attivita` intestinale abituale, con >3 evacuazioni intestinali con feci non formate nella 24 ore precedenti la randomizzazione, e ¿ Presenza della tossina A o B di C. difficile nelle feci nelle 48 ore precedenti la randomizzazione (per i falliti al metronidazolo) o nelle 96 ore (per soggetti con ≤ 24 ore di pretrattamento per C. Difficile). 2. I soggetti di sesso femminile in eta` fertile devono adottare un metodo contraccettivo adeguato ed affidabile, ad es. barriera con schiuma o gel spermicida, dispositivo intrauterino, contraccettivo ormonale. Le donne postmenopausali devono essere entrate in postmenopausa da almeno 1 anno. I soggetti di entrambi i sessi devono accettare di evitare il concepimento durante il trattamento e per un periodo di quattro settimane successivo alla fine del trattamento in studio. 3.Tutti i soggetti dovranno firmare un modulo di consenso informato. 4.gli oppiacei saranno permessi se il soggetto avra` un dosaggio stabile al momento della randomizzazione e si prevede di mantenere questo dosaggio durante il periodo di trattamento: l`oppiaceo PRN e` permesso se il totale della dose giornaliera non cambia durante il periodo di trattamento. 5.i soggetti che, dopo almeno 3 giorni pieni di trattamento con metronidazolo, continuano a presentare diarrea come da definizione senza nessun miglioramento clinico significativo e rimangono positivi alla tossina possono essere arruolati nello studio.

E.4

Principal exclusion criteria

1. Life threatening or fulminant CDAD (WBC>30x109/L; temperature >40C; or evidence of hypotension [systolic blood pressure less than 90 mmHg, and septic shock, peritoneal sign or significant dehydration.) 2. toxic megacolon. 3. Previous exposure to PAR-101/OPT-80. 4. Females who are pregnant or breastfeeding. 5.Likelihood of death within 72 hours from any cause. 6. Concurrent use of: oral vancomycin, metronidazole, oral bacitracin, fusidic acid, rifaximin, nitazoxanide, or related drugs. If the investigator feels the clinical imperative to begin treatment before knowing the laboratory result for stool toxin, up to 4 doses but no more than 24 hours of treatment with metronidazole and/or vancomycin will be allowed. While such pretreated subjects may be enrolled (i.e. no more than 24 hours of previous therapy), it is preferred that subjects who have not received prior CDAD treatment on this admission. 7. The anticipated need to continue other antibacterials for a period exceeding seven days from study start. 8. Subjects who in the opinion of the investigator require other drugs to control diarrhea (e.g. loperamide) or which could affect peristalsis. 9.Unable or unwilling to comply with sudy protocol, including ingesting capsules, having blood drawn, and providing stool samples as scheduled. 10. Participation in other clinical research studies utilising an investigational agent within one month prior to screening or within five half lives of the investigational agent, whichever is longer. 11. History of ulcerative colitis or Crohn's disease. 12. multiple occurrences (defined as more than one prior occurrence) of CDAD within the past three months. Subjects presenting with the first recurrence within the three months may be enrolled.

1. CDAD che metta in pericolo di vita o fulminante WBC>30x109/L; temperatura >40C; o evidenza di ipotensione [pressione sanguigna sistolica <90 mmHg, shock settico, segni peritoneali o significante disidratazione.) 2. megacolon tossico 3.precedente uso di PAR-101/OPT-80. 4.Donne incinte o nel periodo dell'allattamento. 5. Possibilita' di morte entro 72 ore per qulsiasi causa. 6.Uso corrente di vancomycina, metronidazolo, bacitracina orale, acido fusidico , rifaximina, nitazoxanide, o farmaci correlati.Se lo sperimentatore ritiene imperativo iniziare il trattamento prima di conoscere il risultato di laboratorio per la tossina fecale, saranno permesse fino a 4 dosi di trattamento ma non piu' di 24 ore con metronidazolo e/o vancomycina. Mentre tali soggetti pretrattati possono essere arruolati (cioe' non piu' di 24 ore di terapia precedente), si preferiscono per l'arruolamento i soggetti che non hanno ricevuto prima trattamenti per CDAD. 7.L'esigenza anticipata di continuare con altri antibatterici per un periodo superiore a 7 giorni dall'inizio dello studio. 8.Soggetti che nell'opinione dello sperimentatore richiedano altri farmaci per il controllo della diarrea (cioe' loperamide)o che potrebbero inluenzare la peristalsi. 9.Incapaci o che non vogliono collaborare con il protocollo dello studio, incluso l'ingestire capsule, fare prelievi del sangue e procurare campioni fecali come programmato. 10. Partecipazione ad altri studi clinici utilizzando un prodotto sperimentale un mese prima dello screening. 11.precedente colite ulcerativa o Crohn disease. 12.Molteplici episodi (definiti come piu' di un unico episodio) di CDAD negli ultimi 3 mesi.Soggetti che si presentano con la prima ricorrenza in 3 mesi possono essere arruolati.

E.5 End points

E.5.1

Primary end point(s)

Demonstrate that the cure rate of CDADfollowing treatment with PAR-101 is no worse than that following treatment with vancomycin.

Dimostrare che il tasso di guarigione della CDAD dopo trattamento con PAR-101/OPT-80 non e' inferiore a quello dopo trattamento con vancomicina.

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

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

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

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

Ultima visita post-dosaggio (36-40 giorni) dell'ultimo soggetto

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:

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)

Yes

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

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 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 2008-01-07.

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

300

F.4.2.2

In the whole clinical trial

664

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)

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

2007-07-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-07-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-12-11

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