Clinical Trials Register

Summary
EudraCT Number:	2012-000252-34
Sponsor's Protocol Code Number:	LCD-CDAD-10-07
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-10-11
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

Czechia - SUKL

A.2

EudraCT number

2012-000252-34

A.3

Full title of the trial

A Randomized, Double-Blinded, Active-Controlled Study of CB-183,315 in Patients with Clostridium Difficile Associated Diarrhea

A.3.1

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

A.4.1

Sponsor's protocol code number

LCD-CDAD-10-07

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01597505

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	Cubist 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	Cubist Pharmaceuticals, Inc.
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	Cubist Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Jennifer Callahan
B.5.3	Address:
B.5.3.1	Street Address	65 Hayden Avenue
B.5.3.2	Town/ city	Lexington, MA
B.5.3.3	Post code	02421
B.5.3.4	Country	United States
B.5.4	Telephone number	1895895-6556
B.5.5	Fax number	1781240-0774
B.5.6	E-mail	jennifer.callahan@cubist.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	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	CB-183,315
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	pending
D.3.9.1	CAS number	1233389-51-9
D.3.9.2	Current sponsor code	CB-183,315
D.3.9.3	Other descriptive name	N/A
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	250
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	Vancocin
D.2.1.1.2	Name of the Marketing Authorisation holder	ViroPharma Incorporated
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	N/A
D.3.9.1	CAS number	1404-93-9
D.3.9.3	Other descriptive name	VANCOMYCIN HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB05077MIG
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	125
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	Capsule
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

Clostridium
difficile Associated Diarrhea

E.1.1.1

Medical condition in easily understood language

Clostridium
difficile Associated Diarrhea

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	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10012734
E.1.2	Term	Diarrhea, Clostridium difficile
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

Primary Objectives:
Efficacy
• To demonstrate the non-inferiority of CB-183,315 versus oral vancomycin in adult subjects with CDAD based on the difference in clinical response rates at end-of-therapy (EOT) in the mMITT
population using a non inferiority margin of 10%.
Safety
• To evaluate the safety of CB-183,315 in subjects with CDAD.

E.2.2

Secondary objectives of the trial

Key secondary objectives
• To demonstrate that clinical response over time (defined as clinical response through the end of therapy and the sustained clinical response from end of therapy to Day 40) to CB-183,315 is
superior to oral vancomycin.
• To demonstrate that sustained clinical response to CB-183,315 at the end of the study is superior to oral vancomycin.
For other secondary objectives, please refer to the Protocol

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

To be eligible for enrollment, a subject must meet all of the following
criteria prior to any study related procedures:
1. Informed Consent obtained and signed;
2. Age ≥18 and <90 years;
3. If female, subject must not be pregnant or nursing, and must be
either:
a. Not of childbearing potential: defined as postmenopausal for at least 1
year or surgically sterile due to bilateral tubal ligation, bilateral
oophorectomy, or hysterectomy (no pregnancy test required if 1 of these
conditions are met); or
b. If of childbearing potential (and confirmed to not be pregnant by a
negative serum or urine pregnancy test):
i. Must either abstain from sexual intercourse; or
ii. Must practice a barrier method of birth control (e.g., a diaphragm or
contraceptive sponge) and 1 of the following methods: oral or parenteral
contraceptives (oral or parenteral contraceptives must have been used
for at least 3 months prior to study drug administration), or
iii. Must have a vasectomized partner.
4. Has diarrhea with a minimum of 3 unformed bowel movements or
>200 mL volume of stool for subjects with a collection device (eg. rectal
tube or colostomy bag) over a period of 24 hours just prior to
randomization/first dose of study drug; and
5. Has a positive result for C. difficile toxin by EIA, PCR, or a cell culture
cytotoxin neutralization assay from a sample obtained within 48 hours
prior to first dose of study drug.

E.4

Principal exclusion criteria

A subject will not be enrolled if the subject meets any of the following
criteria:
1. Toxic megacolon and/or known small bowel ileus;
2. Received treatment with intravenous immune globulin (IVIG) within
30 days prior to the first dose of study drug;
3. Received treatment with a fecal transplant within 7 days, and/or is
anticipated to receive a fecal transplant during the study.
4. Antibacterial therapy specific for current CDAD:
• Received >4 doses or >24 hours of oral vancomycin for the current
episode of CDAD prior to first dose of study drug.
• Received >4 doses or >24 hours of oral/IV metronidazole for the
current episode of CDAD prior to first dose of study drug unless patient
received at least 3 days of such therapy, and is
considered a treatment failure for CDAD.
• Received >24 hours of any other antibacterial for the current CDAD
within 14 days prior to the first dose of study drug, unless considered a
treatment failure for CDAD.
5. Received an investigational vaccine against C. difficile;
6. Received an investigational product containing monoclonal antibodies
against toxin A or B within 180 days prior to first dose of study drug;
7. Patients with more than 2 episodes of CDAD, including the current
episode, within 90 days of start of study therapy (i.e., patients can be
enrolled with their 1st recurrence/2nd episode);
8. Major gastrointestinal (GI) surgery (i.e. significant bowel resection)
within 3 months of enrollment;
9. History of prior inflammatory bowel disease: ulcerative colitis, Crohn's
disease, or microscopic colitis;
10. Continues to take loperamide, diphenoxylate/atropine, or
cholestyramine during the duration of the study;
11. Continues to take opiate treatment unless on a stable dose as of
onset of diarrhea and no increase in dose planned for the duration of the
study;
12. Known positive stool cultures for other enteropathogens including
but not limited to Salmonella, Shigella, and Campylobacter;
13. Known stool studies positive for pathogenic ova and/or parasites;
14. Known intolerance or hypersensitivity to daptomycin and/or
vancomycin;
15. Life-threatening illness at the time of enrollment as measured by a
score of 4 using a modified Horn's index;
16. Poor concurrent medical risks with clinically significant co-morbid
disease such that in the opinion of the Investigator the patient shouldnot be enrolled;
17. Received an investigational drug or participated in any experimental
procedure within 1 month prior to start of study therapy (Investigational
use of approved products may be permitted with the approval of the
Medical Monitor);
18. Subjects with HIV, whose latest CD4 count is <200 cells/mm3 or
there is evidence of clinical immunosuppression;
19. Anticipated that systemic antibacterial therapy for a non-CDAD
infection will be required for >7 days after start of study therapy;
20. Continues to take Saccharomyces or similar probiotic;
21. Concurrent intensive induction chemotherapy, radiotherapy, or
biologic treatment for active malignancy;
22. Unable/unwilling to comply with the protocol requirements;
23. Any condition that, in the opinion of the Investigator, might interfere
with study objectives;
24. Life expectancy is less than 8 weeks.

E.5 End points

E.5.1

Primary end point(s)

Primary Efficacy Endpoint
• Clinical Response at the end of therapy in the mMITT population

E.5.1.1

Timepoint(s) of evaluation of this end point

End of therapy

E.5.2

Secondary end point(s)

Key Secondary Efficacy Endpoints
• Clinical response over time (defined as clinical response through the end of therapy and the sustained
clinical response from end of therapy to Day 40) in the mMITT population
• Sustained clinical response at the end of the study in the mMITT population

Other Efficacy Endpoints
• Sustained clinical response at Day 24 from start of treatment in the mMITT population
• Recurrence of CDAD from end of treatment to the end of study in the mMITT population
• Time to resolution of diarrhea in the mMITT population
• Time to reappearance of diarrhea from the end of treatment to the end of study among subjects with a clinical response in the mMITT population
• Clinical Response at end of therapy in the following subgroups:
o Subjects infected with C. difficile epidemic toxigenic BI/NAP1/027 strain
o Per Protocol 1 Subjects
• Sustained Clinical Response at end of study in the following subgroups:
o Subjects infected with C. difficile epidemic toxigenic BI/NAP1/027 strain
o Per Protocol 2 Subjects
• Health economic outcomes during the study between CB-183,315 and vancomycin, including the length of hospital stay and hospital admission rates

E.5.2.1

Timepoint(s) of evaluation of this end point

The clinical response will be assessed through the
end of therapy and the sustained
clinical response from end of therapy to the end of the study.
Other Efficacy Endpoints will be evaluated at different timepoints as stated above.

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

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

Canada

United States

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

The end of the trial is defined as the last visit of the last subject undergoing the trial

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:

243

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

365

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

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

264

F.4.2.2

In the whole clinical trial

608

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 subjects would just revert to normal 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

2013-02-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-01-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-03-20

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