Clinical Trials Register

Summary
EudraCT Number:	2014-003502-33
Sponsor's Protocol Code Number:	D5553C00002
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-11-27
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2014-003502-33

A.3

Full title of the trial

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel group, Phase 3 Trial to Evaluate the Safety and Efficacy of Once Weekly Exenatide Therapy Added to Titrated Basal Insulin Glargine Compared to Placebo Added to Titrated Basal Insulin Glargine in Patients with Type 2 Diabetes Who Have Inadequate Glycemic Control on Basal Insulin Glargine with or without Metformin

Multicentrikus, randomizált, kettős vak, placebo-kontrollált, párhuzamos csoportos, III. fázisú vizsgálat a titrált bázis glargin inzulin mellett hetente egyszer alkalmazott exenatid biztonságosságának és hatásosságának értékelésére, titrált bázis glargin inzulin mellett alkalmazott placebóval összehasonlítva olyan 2-es típusú cukorbetegségben szenvedő betegek esetében, akiknél metforminnal vagy anélkül alkalmazott bázis glargin inzulin nem biztosít megfelelő glikémiás kontrollt

A.3.1

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

Phase 3 study to compare adding Exenatide once weekly injection to adjusted dose of basal insulin Glargine compared to placebo (no active medication) to adjusted dose of basal insulin Glargine.

A.3.2

Name or abbreviated title of the trial where available

DURATION 7

A.4.1

Sponsor's protocol code number

D5553C00002

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02229383

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	AstraZeneca AB
B.1.3.4	Country	Sweden
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	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca
B.5.2	Functional name of contact point	Information Center
B.5.3	Address:
B.5.3.1	Street Address	NA
B.5.3.2	Town/ city	NA
B.5.3.3	Post code	NA
B.5.3.4	Country	United States
B.5.6	E-mail	information.centre@astrazeneca.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	BYDUREON (2 mg powder and solvent for prolonged-release suspension for injection)
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb/AstraZeneca EEIG
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.3.1	Product name	Exenatide
D.3.4	Pharmaceutical form	Powder and solvent for suspension for injection in pre-filled syringe
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	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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	Powder and solvent for suspension for injection in pre-filled syringe
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

Diabetes Mellitus

Diabétesz

E.1.1.1

Medical condition in easily understood language

High blood sugar

Magas vércukor

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	17.1
E.1.2	Level	HLT
E.1.2	Classification code	10012602
E.1.2	Term	Diabetes mellitus (incl subtypes)
E.1.2	System Organ Class	100000004860

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the change from baseline in HbA1c achieved with exenatide once weekly added to titrated basal insulin glargine, with or without metformin, to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.

E.2.2

Secondary objectives of the trial

To compare the effect of exenatide once weekly added to titrated basal insulin glargine, with or without metformin, to placebo added to titrated basal insulin glargine, with or without metformin, on changes in glycemic control and anthropometric measures.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provision of informed consent prior to any study-specific procedures
2. Is able to read, understand, and sign the Informed Consent Forms (ICFs) and, if applicable, an Authorization to Use and Disclose Protected Health Information form (consistent with Health Insurance Portability and Accountability Act of 1996 [HIPAA] legislation), communicate with the Investigator, and understand and comply with protocol requirements
3. Is at least 18 years old at Visit 1 (Screening). For patients taking metformin, the upper age limit should be based on local metformin label restrictions
4. Has a diagnosis of Type 2 Diabetes Mellitus (T2DM)
5. Has HbA1c of 7.5% to 12.0%, inclusive, at Visit 1 (Screening). (Note: The acceptable HbA1c range is different for randomization; see Section 3.2 for the randomization criterion)
6. Has fasting plasma glucose (FPG) concentration <280 mg/dL (15.6 mmol/L) at Visit 1 (Screening)
7. Treated with basal insulin glargine at a dose of ≥20 units/day for at least 6 weeks prior to Screening, in combination with diet and exercise alone or in combination with:
 a stable dose of metformin (≥1500 mg/day) for at least 8 weeks prior to Visit 1 (Screening)
 a stable dose of metformin (≥1500 mg/day) for at least 8 weeks prior to Visit 1 (Screening) and a stable dose of sulfonylurea for at least 8 weeks prior to the Screening visit
8. Is male, or is female and meets all the following criteria:
 Not breastfeeding
 Negative pregnancy test result (beta-subunit [-hCG], human chorionic gonadotropin) at Visit 1 (Screening) (not applicable to hysterectomized females.)
 If of childbearing potential (including perimenopausal women who have had a menstrual period within 1 year), must practice and be willing to continue to practice appropriate birth control (defined as a method that results in a low failure rate, ie, less than 1% per year, when used consistently and correctly, such as implants, injectables, hormonal contraceptives [pills, vaginal rings, or patches], some intrauterine contraceptive devices [levonorgestrel-releasing or copper-T], tubal ligation or occlusion, or a vasectomized partner) during the entire duration of the study. As applicable, all methods must be in effect prior to receiving the first dose of study medication
 Must practice appropriate birth control as stated above for 10 weeks after the last dose of study medication
9. Patients who are receiving the following medications must be on a stable treatment regimen for a minimum of 2 months prior to Visit 1 (Screening):
 Antihypertensive agents
 Thyroid replacement therapy
 Antidepressant agents.

E.4

Principal exclusion criteria

1. Serum calcitonin concentration ≥40 pg/mL (≥40 ng/L) at Visit 1 (Screening)
2. Clinically significant abnormal free T4 values or patients needing initiation or adjustment of thyroid treatment according to the Investigator. Abnormal thyroid stimulating hormone (TSH) value at Screening will be further evaluated by free T4. Patients with clinically significant abnormal free T4 values will be excluded
3. Known active proliferative retinopathy
Gastrointestinal/Hepatic Conditions
4. History of, or currently have, acute or chronic pancreatitis, or have triglyceride concentrations ≥500 mg/dL (≥5.65 mmol/L) at Visit 1 (Screening)
5. History or presence of inflammatory bowel disease or other severe gastrointestinal diseases, particularly those which may impact gastric emptying, such as gastroparesis or pyloric stenosis
6. History of gastric bypass surgery or gastric banding surgery, or either procedure is planned during the time period of the study. Current use of gastric balloons is also excluded
7. Significant hepatic disease, including, but not limited to, acute hepatitis, chronic active hepatitis, or severe hepatic insufficiency, including patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or total bilirubin (TB) >2 mg/dL (>34.2 μmol/L). (Patients with TB >2 mg/dL [>34.2 μmol/L] and documented Gilbert’s syndrome will be allowed to participate)
8. Positive serological test for hepatitis B or hepatitis C
9. Known history of hepatotoxicity with any medication
10. Known history of severe hepatobiliary disease
Cardiovascular Conditions
11. Clinically significant cardiovascular disease or procedure within 3 months of Visit 1, including but not limited to myocardial infarction, clinically significant arrhythmia, unstable angina, coronary artery bypass surgery, or angioplasty; or are expected to require coronary artery bypass surgery or angioplasty during the course of the study
12. Presence or history of severe congestive heart failure (New York Heart Association Class IV [CCNYHA 1994])
Kidney Conditions
13. History of renal transplantation, or is currently receiving renal dialysis, or has a creatinine clearance <30 mL/min (0.50 mL/s) as calculated by the Cockcroft-Gault formula
14. If on metformin, has a serum creatinine level ≥1.5 mg/dL in males, ≥1.4 mg/dL in females, or creatinine clearance <60 mL/min (<1.0 mL/s) as calculated by the Cockcroft-Gault formula
Infection Disease/Immunologic Conditions
15. Known or suspected human immunodeficiency virus (HIV) infection
16. Presence or history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN 2) OR a family history of medullary thyroid carcinoma or MEN 2
17. Malignancy (with the exception of basal and squamous cell carcinoma of the skin) within 5 years of Visit 1 (Screening)
18. Hemoglobinopathy, hemolytic anemia, or chronic anemia (hemoglobin concentration <11.5 g/dL [115 g/L] for males, <10.5 g/dL [105 g/L] for females) or any other condition known to interfere with the HbA1c methodology
19. Any exposure to exenatide (including Byetta®, Bydureon™, or exenatide suspension) or any GLP-1 analog
20. Administration of any antihyperglycemic therapy, other than sulfonylurea (SU), insulin, or metformin, for more than 14 days (consecutive or not) during the 12 weeks prior to Visit 1 (Screening). In addition, administration of any antihyperglycemic therapy, other than sulfonylurea (SU), insulin, or metformin, at any dose, at any time during the 4 weeks prior to Visit 1 (Screening)
21. Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following treatment-excluded medications:
 Any DPP-4 inhibitor within 3 months prior to Visit 1 (Screening)
 Systemic corticosteroids within 3 months prior to Visit 1 (Screening) by oral, intravenous, intra-articular, or intramuscular route; or potent, inhaled, or intrapulmonary (including ADVAIR®) steroids known to have a high rate of systemic absorption. (For examples of excluded steroids, refer to Section 7.7)

E.5 End points

E.5.1

Primary end point(s)

Change in HbA1c, the variable of choice for assessment of long-term glycemic control.

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline to week 28

E.5.2

Secondary end point(s)

Secondary efficacy endpoints
To compare exenatide once weekly added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, for the following endpoints:
• Change in body weight from baseline to Week 28
• Change in 2-hour postprandial glucose (PPG) after a standard meal tolerance test at Week 28
• Proportion of patients with HbA1c <7.0% at Week 28
• Change in total mean daily insulin dose from baseline to Week 28.
• Proportion of patients with HbA1c <7.0% at Week 28 with no weight gain at Week 28 and no major hypoglycemia over 28 weeks.
• Change in systolic blood pressure at Week 28.

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline to Week 28.

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

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)

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

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

E.8.5

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

Hungary

Poland

Romania

Slovakia

South Africa

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

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

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:

396

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

128

F.4.2.2

In the whole clinical trial

440

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

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

2014-12-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-12-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-08-29

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