Clinical Trials Register

Summary
EudraCT Number:	2015-000408-24
Sponsor's Protocol Code Number:	D5551C00002
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-02-22
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

Bulgarian Drug Agency

A.2

EudraCT number

2015-000408-24

A.3

Full title of the trial

A Phase 3, Double-Blind, Placebo-Controlled, Randomized, Multi-Center Study to Assess the Safety and Efficacy of Exenatide Once Weekly in Adolescents with Type 2 Diabetes

A.3.1

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

Safety and Efficacy Study of Exenatide Once Weekly in Adolescents with Type 2 Diabetes

A.4.1

Sponsor's protocol code number

D5551C00002

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01554618

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/197/2014

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	AstraZeneca 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.center@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	AstraZeneca AB
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.3.10	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.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	Yes
D.2.1.1.1	Trade name	BYDUREON (2 mg powder and solvent for prolonged-release suspension for injection). Otherwise known as dual chamber pen.
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
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.3.10	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
D.8 Placebo: 2
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

Type 2 diabetes

E.1.1.1

Medical condition in easily understood language

High Blood Sugar

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	20.0
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 assess the effect on glycemic control, as measured by glycosylated hemoglobin (HbA1c), of exenatide once weekly (EQW) following 24 weeks of treatment compared to placebo in children and adolescents with type 2 diabetes mellitus

To evaluate the safety and tolerability of EQW compared to placebo following 24 weeks of treatment in children and adolescents with type 2 diabetes mellitus

E.2.2

Secondary objectives of the trial

To compare the effects of EQW following 24 weeks of treatment to those achieved by placebo in children and adolescents with T2D on the following: Fasting plasma glucose concentration, Proportion of patients achieving HbA1c goals, Body weight and Tanner pubertal stage, Blood pressure and lipids

To assess the effects of long-term EQW therapy (~1 year) in children and adolescents with T2D on the following: Long-term safety and tolerability, Parameters related to glycemic control, including HbA1c, fasting plasma glucose concentration, and proportion of patients achieving HbA1c goals, Body weight and Tanner pubertal stage, Blood pressure and lipids

To examine the effect of exenatide once weekly on beta-cell function (HOMA-B) and insulin sensitivity (HOMA-S) as measured by the homeostatic model assessment (HOMA) in children and adolescents with T2D who are not taking insulin

Assess pk of exenatide once weekly in children and adolescents with T2D

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Mixed Meal Substudy, Amendment 3.0, 09 April 15 (Appendix F of protocol)

The primary objective of this exploratory substudy is: To evaluate the effect of exenatide once weekly on postprandial beta-cell function as assessed by C peptide secretion during a mixed meal test, following approximately 28 weeks of exenatide once weekly treatment and at approximately 10 to 12 weeks following cessation of drug therapy.

The secondary objective of this exploratory substudy is: To assess postprandial glucose and glucagon responses during a mixed meal test following approximately 28 weeks of exenatide once weekly treatment and at approximately 10 to 12 weeks following cessation of drug therapy.

Blood samples for pharmacokinetic measurements of plasma exenatide concentrations for potential future analysis will be collected within the 30 min prior to the start of the standardized meal

E.3

Principal inclusion criteria

Each patient must meet the following criteria to be enrolled in this study.
1. Is a child or an adolescent of 10 to <18 years old, at Visit 1 (Screening)
2. Has been diagnosed with type 2 diabetes mellitus per American Diabetes Association diagnostic criteria
3. HbA1c of 6.5% to 11.0%, inclusive, in patients not taking insulin/SU, and of 6.5% to 12.0%, inclusive, in patients taking insulin/SU, at Visit 1 (Screening)
4. Has a C-peptide of >0.6 ng/mL at Visit 1 (Screening)
5. Has been treated with diet and exercise alone or in combination with a stable dose of an oral antidiabetic agent (e.g., metformin and/or SU) and/or insulin for their type 2 diabetes for at least 2 months prior to Visit 1 (Screening)
6. Has a fasting plasma glucose concentration <280 mg/dL (15.5 mmol/L) at Visit 1(Screening)

E.4

Principal exclusion criteria

Patients who meet any of the following criteria will be excluded from the study.
1. Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the Investigator, including but not limited to the following conditions: a. Hepatic disease (defined by aspartate or alanine transaminase >3.0 times the upper limit of normal (ULN), b. Renal disease or serum creatinine >1.5 mg/dL (132.6 μmol/L) (males) or 1.4 mg/dL (123.8 μmol/L) (females), c. Gastrointestinal disease deemed significant by the Investigator, d. Organ transplantation, e. Chronic infection (e.g., tuberculosis, human immunodeficiency virus, hepatitis B virus, or hepatitis C virus), f. Clinically significant malignant disease (with the exception of basal and squamous cell carcinoma of the skin) within 5 years of Visit 1 (Screening)
2. Has positive antibody titers to glutamic acid decarboxylase (GAD65) or islet cell antigen (ICA512) at Visit 1 (Screening)
3. Has a personal or family history of elevated calcitonin, calcitonin >100 ng/L, medullary thyroid carcinoma, or multiple endocrine neoplasia-2
4. Has ever used exenatide (exenatide once weekly [exenatide LAR], exenatide BID, BYETTA, or any other formulation) or any glucagon-like peptide-1 (GLP-1) receptor agonist (e.g., liraglutide [Victoza®])
5. Is pregnant

E.5 End points

E.5.1

Primary end point(s)

Change in HbA1c from baseline Visit 2 (Week 0) to Visit 7 (Week 24)

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to Week 24

E.5.2

Secondary end point(s)

1. Change in HbA1c
2. Change in fasting plasma glucose concentration
3. Proportions of patients achieving HbA1c goals of ≤6.5% and <7.0%
4. Change in body weight
5. Change in fasting insulin and C-peptide
6. Change in beta-cell function (HOMA-B) and insulin sensitivity (HOMA-S) as measured by HOMA in EQW patients not taking insulin
7. Change in lipids
8. Change in blood pressure
9. Plasma exenatide concentrations
10. Proportions of patients discontinuing the study, needing rescue due to failure to maintain glycemic control, and number of rescue episodes
11. Proportions of patients reporting different injection site reactions
12. Change in body mass index (BMI)
13. Change in body weight percentile and height percentile
14. Safety and tolerability endpoints including incidence of treatment emergent AEs, antibodies to exenatide, physical examinations, laboratory measurements (clinical, chemistry/hematology), and vital sign measurements
15. Change in calcitonin, pancreatic amylase, and lipase
16. Change in TSH, free T4, prolactin, cortisol, IGF-1, and DHEAS
17. Tanner pubertal stage

E.5.2.1

Timepoint(s) of evaluation of this end point

1 Visit 2 to Visit 10 & interm.visit
2 Visit 2 to Visit 7, Visit 10, & interm.visit
3 Visit 7,Visit 10, and each intermediate visit
4 Visit 2 to Visit 7, Visit 10, & interm.visit
5 Visit 2 to Visit 7, Visit 10, & interm.visit
6 Visit 2 to Visit 7, Visit 10, & interm.visit
7 Visit 2 to Visit 5, Visit 7, Visit 10
8 Visit 2 to Visit 7, Visit 10, & interm.visit
9 Visit 2,Visit 7, Visit 10 & interm.visit
10 Visit 7, Visit 10 & interm.visit
11 Visit 3 to Visit 10
12,13, 14 Visit 2 to Visit 5,Visit 10, &interm.visit
15 Visit 2 to Visit 5 & Visit 10
16 Visit 2 to Visit 5,Visit 7,&Visit 10
17 Visit 2, Visit 5, Visit 7, Visit 9, & Visit 10

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)

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.8.4.1

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

Bulgaria

Hungary

Israel

Kuwait

Mexico

Ukraine

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. Following V11 (week 62) pts with height increase at least 5 mm between V8 and V11 will enter Extended Safety Follow-up Period (F/U pd). Please refer to Appendix E of protocol for further detail

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

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)

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

patients 10 to <18 years old, for some their parents/guardian will sign the consent and patients an assent in other cases, the patient will sign consent, whichever is in line with local requirements as age of consent varies per country.

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

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)

subjects who end participation at week 62 or those who enter extended safety follow up will not receive IP and will return to standard 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

2016-06-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-03-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-05-05

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