Clinical Trials Register

Summary
EudraCT Number:	2012-000619-10
Sponsor's Protocol Code Number:	RUNMC-EX-BCM-2012
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-06-19
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

Netherlands - Competent Authority

A.2

EudraCT number

2012-000619-10

A.3

Full title of the trial

Clinical proof-of-principle of the determination of the beta cell mass in vivo by SPECT imaging with the 111In-labeled GLP-1 analogue DTPA-[K40]-Exendin 4

A.3.1

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

Determination of the mass of insulin-producing beta cells in the pancreas by means of a radioactive tracer molecule

A.3.2

Name or abbreviated title of the trial where available

GLP-1 receptor targeting in diabetic and healthy individuals

A.4.1

Sponsor's protocol code number

RUNMC-EX-BCM-2012

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	Radboud University Nijmegen Medical Centre
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Radboud University Nijmegen Medical Centre
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Radboud University Nijmegen Medical Centre
B.5.2	Functional name of contact point	Department of Nuclear Medicine
B.5.3	Address:
B.5.3.1	Street Address	Geert Grooteplein 8
B.5.3.2	Town/ city	Nijimegen
B.5.3.3	Post code	6525 GA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31243614048
B.5.5	Fax number	+31243618942
B.5.6	E-mail	m.gotthardt@nucmed.umcn.nl

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	Byetta
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland B.V.
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	111-In-DTPA-[K40]-Exendin4
D.3.4	Pharmaceutical form	Radiopharmaceutical precursor, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent)
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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

patients with long-standing type 1 diabetes

E.1.1.1

Medical condition in easily understood language

patients with diabetes

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	HLGT
E.1.2	Classification code	10018424
E.1.2	Term	Glucose metabolism disorders (incl diabetes mellitus)
E.1.2	System Organ Class	10014698 - Endocrine disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
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	10014698 - Endocrine disorders

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	10012601
E.1.2	Term	Diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

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	10067584
E.1.2	Term	Type 1 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 is to proof that the pancreatic uptake of EX in patients with long-standing DM1 and non-measurable production of C-peptide, i.e. patients with no relevant beta-cell mass left, is clearly lower than in healthy individuals with intact glucose homeostasis and insulin production.

E.2.2

Secondary objectives of the trial

The secondary objectives are:
• To determine the difference in uptake between the two groups in order to estimate the minimum difference in beta-cell mass (>15%) that would be measurable by GRS. (The beta cell mass in healthy subjects may vary considerably (circa 1-8% of the total pancreatic mass (Ritzel et al 2006)), so that it cannot be predicted what the difference in pancreatic uptake of 111In-DTPA-Exendin between healthy volunteers and patients with long standing T1D will be.)
• To perform dosimetric calculations in order determine the effective dose to the patient for EX-scanning and to determine the dose to the individual islets.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• 21-60 years of age
• Long-standing T1D (>5 years) or healthy volunteer with normal glucose tolerance
• Body mass index (BMI) of 21-27
• No previous treatment with synthetic Exendin (Exenatide, Byetta®) or Dipeptidyl-Peptidase IV inhibitors
• No measurable C-peptide in T1D patients (stimulated)
• Normal HbA1c (<7%) in healthy volunteers

E.4

Principal exclusion criteria

• Age <21 or >60 years
• T1D duration <5 years or pathologic glucose tolerance in healthy volunteers
• BMI <21 or >27
• Previous treatment with Exenatide or Dipeptidyl-Peptidase IV inhibitors
• Measurable C-peptide in T1D patients
• Elevated HbA1c values (>7%) in healthy volunteers

E.5 End points

E.5.1

Primary end point(s)

Determination of the difference in uptake of the radiotracer into the pancreas between healthy volunteers and patinets with type 1 diabetes.

E.5.1.1

Timepoint(s) of evaluation of this end point

4h, 24h, 48h, 96h, 168h

E.5.2

Secondary end point(s)

Determination of the minimal difference in beta cell mass that can be measured via the uptake of the radiotracer into the pancreas

E.5.2.1

Timepoint(s) of evaluation of this end point

4h, 24h, 48h, 96h, 168h

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

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

Yes

E.6.13.1

Other scope of the trial description

Proof of principle that scintigraphic measurement of the utpake of 111In-DTPA-[K40]-Exendin 4 into the pancreas allows to determine differences in beta cell mass.

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

healthy subjects

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

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

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:

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

Yes

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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.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

2012-06-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-24

P. End of Trial
P.	End of Trial Status	Ongoing

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