Clinical Trials Register

Summary
EudraCT Number:	2012-002219-25
Sponsor's Protocol Code Number:	ITCA650-CLP-107
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-06-28
Trial 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

Poland - Office for Medicinal Products

A.2

EudraCT number

2012-002219-25

A.3

Full title of the trial

A Randomized, Multicenter Study to Evaluate Cardiovascular Outcomes with ITCA 650 in Patients Treated with Standard of Care for Type 2 Diabetes

A.3.1

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

A Study to Evaluate Cardiovascular Outcomes with ITCA 650 in Patients Treated with Standard of Care for Type 2 Diabetes

A.4.1

Sponsor's protocol code number

ITCA650-CLP-107

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01455896

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	Intarcia Therapeutics, 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	Intarcia Therapeutics, 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	Intarcia Therapeutics, Inc
B.5.2	Functional name of contact point	Chief Medical Officer
B.5.3	Address:
B.5.3.1	Street Address	24650 Industrial Blvd
B.5.3.2	Town/ city	Hayward CA
B.5.3.3	Post code	94545
B.5.3.4	Country	United States
B.5.4	Telephone number	+1510782 7800
B.5.5	Fax number	+1510782 7801
B.5.6	E-mail	clinicaltrials@intarcia.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	ITCA 650 20 mcg/day
D.3.2	Product code	ITCA 650 20 mcg/day
D.3.4	Pharmaceutical form	Implant
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EXENATIDE
D.3.9.1	CAS number	141758-74-9
D.3.9.4	EV Substance Code	SUB21818
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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	Yes
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	synthetic peptide
D.IMP: 2
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	ITCA 650 60 mcg/day
D.3.2	Product code	ITCA 650 60 mcg/day
D.3.4	Pharmaceutical form	Implant
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EXENATIDE
D.3.9.1	CAS number	141758-74-9
D.3.9.4	EV Substance Code	SUB21818
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
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	Yes
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	synthetic peptide

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	Implant
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Type 2 diabetes

E.1.1.1

Medical condition in easily understood language

Type 2 diabetes

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	PT
E.1.2	Classification code	10067585
E.1.2	Term	Type 2 diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

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 Study 107 is to obtain CV event data that will be pooled with CV event data from other pivotal Phase 3 studies in a meta-analysis to demonstrate that the upper limit of the 95% confidence interval of the hazard ratio of major adverse cardiac events (MACE) in adult patients on Standard of Care for T2D receiving either ITCA 650 or control, based on the time to first occurrence of any event in the MACE1 CV composite endpoint (CV death, non-fatal myocardial infarction [MI], non-fatal stroke, or hospitalization for unstable angina), does not exceed 1.8.

E.2.2

Secondary objectives of the trial

The secondary objective of Study 107 is to use CV event data obtained from Study 107 alone to demonstrate that the upper limit of the 95% confidence interval of the hazard ratio of MACE in adult patients on Standard of Care for T2D receiving either ITCA 650 or control, based on the time to first occurrence of any event in the MACE2 CV composite endpoint that excludes hospitalization for unstable angina (CV death, non-fatal MI, or non-fatal stroke), does not exceed 1.3.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients with a diagnosis of T2D
2. Patients with HbA1c ≥6.5% at Screening.
3. High-risk group defined as males and females ≥40 years old with at least one documented occurrence of: CAD, cerebrovascular disease, or symptomatic peripheral arterial disease whose disease, in the Investigator's opinion, is stable, and not in the acute recovery stage of a CV event (i.e., event listed below to have occurred at LEAST 1 month prior to Screening, unless otherwise specified)
4. Low-risk group defined as males and females ≥60 years old with at least one other risk factor in addition to T2D
5. Current treatment with an intermediate-acting and / or long-acting insulin or intermediate and / or long-acting insulin analogue is allowed; if the screening HbA1c value is ≤8.0%, then the total daily dose of intermediate-acting and/or long-acting insulin or intermediate and/or long-acting insulin analogue will be reduced by 20% at randomization
6. Patients who are on a stable treatment regimen of diet and exercise alone or who are being treated with oral monotherapy or oral combination antidiabetic therapy with the exception of a dipeptidylpeptidase-4 (DPP-4) inhibitor or a glucagonlike peptide (GLP)-1 agonist , or sodium-glucose transporter-2 inhibitor (SGLT2 inhibitor).
7. Women of childbearing potential (WOCBP) must agree to use an adequate method of contraception during the study

E.4

Principal exclusion criteria

1. Prior treatment with DPP-4 inhibitor or GLP-1 agonist or SGLT2 inhibitors (e.g. canagliflozin) within 3 months prior to Screening
2. Current treatment with rapid-acting insulin or rapid-acting insulin analogues;
3. Requirement of treatment with immunosuppressants or medications that affect gastrointestinal (GI) motility (see Appendix B);
4. Diagnosis of or history of:
• Type 1 diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes, e.g., acromegaly and Cushing's Syndrome;
• Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within 6 months prior to screening;
• Major hypoglycemia (defined as requiring third party assistance) within 1 month prior to Screening.
5. History of acute or chronic pancreatitis;
6. History of thyroidcancer, multiple endocrine neoplasia type 2 (MEN2) or a family history of medullary thyroid cancer or MEN2
7. Presence of a thyroid nodule detected on physical examination that
has not been fully evaluated;
8. Currently scheduled for cardiac surgery or arterial revascularization (carotid, coronary, or peripheral) procedures;
9. Current New York Heart Association (NYHA) Class III or IV heart failure;
10. Diagnosed and/or treated malignancy (except for treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, or in situ prostate cancer) within the past 5 years;
11. Uncontrolled hypertension at Screening defined as a systolic BP >180 mmHg and/or a sitting diastolic BP >100 mmHg (may be repeated after 15 minutes and exclusion based on last measurement);

E.5 End points

E.5.1

Primary end point(s)

Time to first occurrence of any event in the MACE composite endpoint (CV death, non-fatal MI, non-fatal stroke, or hospitalization for unstable angina).

E.5.1.1

Timepoint(s) of evaluation of this end point

First occurrence of any event in the MACE composite endpoint

E.5.2

Secondary end point(s)

Time to first occurrence of any event in the MACE2 composite endpoint (CV death, non-fatal MI, or non-fatal stroke)

E.5.2.1

Timepoint(s) of evaluation of this end point

The first occurrence of any event listed 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

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

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

Immunogenicity: Anti-exenatide antibodies will be measured

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)

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)

Yes

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.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

140

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

Bulgaria

Canada

Denmark

France

New Zealand

Romania

Slovakia

Argentina

Australia

Brazil

Czech Republic

Egypt

Estonia

Finland

Germany

Hungary

India

Korea, Republic of

Lithuania

Malaysia

Saudi Arabia

Spain

Israel

Mexico

Poland

Russian Federation

Serbia

South Africa

Turkey

Ukraine

United Arab Emirates

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

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

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:

1500

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1500

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

991

F.4.2.2

In the whole clinical trial

3000

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 to be informed that their study doctor (and/or regular physician) will work with them to determine the best course of therapy after the end of their treatment in the study. No additional treatment will be offered by the sponsor.

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

2013-06-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-03-11

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