Clinical Trials Register

Summary
EudraCT Number:	2017-002025-38
Sponsor's Protocol Code Number:	D5670C00011
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-06-07
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

Germany - BfArM

A.2

EudraCT number

2017-002025-38

A.3

Full title of the trial

A Phase 2, Randomised, Double-Blinded, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Different Doses of MEDI0382 in Overweight and Obese Subjects with Type 2 Diabetes Mellitus

A.3.1

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

A study to look at how safe, well tolerated, and what effect on the body, different doses of study drug MEDI0382 has in patients who are obese and overweight and have type 2 diabetes

A.4.1

Sponsor's protocol code number

D5670C00011

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	MedImmune Limited, a wholly owned subsidiary of AstraZeneca
B.1.3.4	Country	United Kingdom
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	MedImmune Limited, a wholly owned subsidiary of AstraZeneca
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	MedImmune LTD, a wholly owned subsidiary of AstraZeneca
B.5.2	Functional name of contact point	Information Center
B.5.3	Address:
B.5.3.1	Street Address	Milstein Building, Granta Park
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB21 6GH
B.5.3.4	Country	United Kingdom
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	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.3.2	Product code	MEDI0382
D.3.4	Pharmaceutical form	Solution for injection
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	-
D.3.9.1	CAS number	1686108-82-6
D.3.9.2	Current sponsor code	MEDI0382
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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	Solution for injection
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 Mellitus

E.1.1.1

Medical condition in easily understood language

High sugar levels in the blood

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	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

To assess the effects of MEDI0382 titrated up to a dose level of 300 µg on glucose control and body weight versus placebo after 49 days of treatment (Cohort 1 only)

E.2.2

Secondary objectives of the trial

• To assess the effects of MEDI0382 titrated up to a dose level of 300 µg on additional measures of glucose control and body weight versus placebo after 49 days of treatment (Cohort 1 only)

• To characterise the safety profile and tolerability of MEDI0382 titrated up to a dose level of 300 µg during dosing and follow-up (Cohorts 1 and 2)

• To characterise the PK profile and immunogenicity of 50 and 300µg of MEDI0382 (Cohorts 1 and 2)

• To characterise the effect of 50 µg of MEDI0382 on glucose lowering versus placebo after 7 days (Cohorts 1 and 2)

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

Optional Samples Obtained for Future Genetic Research or Future Non-Genetic Research

Subjects will be offered the possibility of participating in optional future genetic exploratory research (“future genetic research”) and optional future non-genetic exploratory research (“future non-genetic research”). After signing consents for future genetic research and future non genetic research, blood samples will be collected in accordance with the entry criteria and study plan. These samples would be used for research on disorders of metabolism or related complications.

E.3

Principal inclusion criteria

1. Male and female subjects aged ≥ 18 years at screening

2. Provision of signed and dated written informed consent (with the exception of consent for genetic and non-genetic research) prior to any study specific procedures

3. BMI between 27 and 40 kg/m2 (inclusive) at screening

4. HbA1c range of 6.5% to 8.5% (inclusive) at screening

5. Diagnosed with T2DM with glucose control managed with metformin monotherapy where no significant dose change (increase or decrease ≥ 500 mg/day) has occurred in the 3 months prior to screening

6. Subjects prescribed oral dual therapy with a dipeptidyl peptidase-4 (DPPIV) inhibitor, sulphonylurea, glitinide, or a sodium-glucose co transporter 2 (SGLT-2) inhibitor in addition to metformin at screening may be eligible to enter the study following a 4-week washout period

7. Female subjects of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating

8. Females of childbearing potential who are sexually active with a nonsterilised male partner must use at least one highly effective method of contraception (see Section 10.2 for definition of females of childbearing potential and for a description of highly effective methods of contraception) from screening and must agree to continue using such precautions through to the end of the study. It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

E.4

Principal exclusion criteria

1. History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject’s ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures

2. Any subject who has received another investigational product as part of a clinical study or a GLP-1 analogue-containing preparation within the last 30 days or 5 half-lives of the drug (whichever is longer) at the time of screening

3. Any subject who has received any of the following medications within the specified time frame prior to the start of the study (Visit 2) (see Section 4.7.2 for further details):
◦ Herbal preparations or drugs licensed for control of body weight or appetite (eg, orlistat, bupropion naltrexone, phentermine-topiramate, phentermine, lorcaserin)
◦ Aspirin (acetylsalicylic acid) at a dose greater than 150 mg once daily
◦ Paracetamol (acetaminophen) or paracetamol containing preparations at a total daily dose of greater than 3g
◦ Ascorbic acid (vitamin C) supplements at a total daily dose of greater than 1000 mg
◦ Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying

4. Concurrent participation in another study of any kind and repeat randomisation in this study is prohibited

5. Severe allergy/hypersensitivity to any of the proposed study treatments,excipients, or ingredients of standardised meals

6. Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus (T1DM) or diabetic ketoacidosis, or if the subject has been treated with daily SC insulin within 90 days prior to screening

7. Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper GI tract (including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data

8. Significant hepatic disease (except for non-alcoholic steatohepatitis [NASH] or non alcoholic fatty liver disease [NAFLD]) without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening:
◦ Aspartate transaminase (AST) ≥ 3 × upper limit of normal (ULN)
◦ Alanine transaminase (ALT) ≥ 3 × ULN
◦ Total bilirubin ≥ 2 × ULN

9. Impaired renal function defined as estimated glomerular filtration rate (eGFR) < 60 mL/minute/1.73m2 at screening (GFR estimated according to Modification of Diet in Renal Disease (MDRD) using MDRD Study Equation IDMS-traceable [SI units])

10. Poorly controlled hypertension defined as:
◦ Systolic BP > 160 mm Hg
◦ Diastolic BP ≥ 95 mm Hg
after 10 minutes of seated rest and confirmed by repeated measurement at screening. Subjects who fail BP screening criteria may be considered for 24-hour ABPM at the discretion of the investigator. Subjects who maintain a mean 24-hour systolic BP ≤ 160 or diastolic BP < 95 mm Hg with a preserved nocturnal dip of > 15% will be considered eligible

11. Unstable angina pectoris, myocardial infarction, transient ischemic attack (TIA) or stroke within 3 months prior to screening, or subjects who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening

12. Severe congestive heart failure (New York Heart Association Class III or IV)

13. Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia

14. Haemoglobinopathy, haemolytic anemia, or chronic anaemia (haemoglobin concentration < 11.5 g/dL [115 g/L] for males, < 10.5 g/dL [105 g/L] for females) at screening or any other condition known to interfere with interpretation of HbA1c measurement

15. History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer

16. Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) antibody

17. History of substance dependence, alcohol abuse, or excessive alcohol intake (defined as an average weekly intake of > 21 alcoholic drinks for men or > 10 alcoholic drinks for women) within 3 years prior to screening, and/or a positive screen for drugs of abuse or alcohol at screening or on admission to the study unit. Subjects who use tricyclic antidepressants or benzodiazepines for an established clinical indication may be permitted to enter the study based upon the judgement of the investigator.

18. Involvement of any AstraZeneca, MedImmune, contract research organization (CRO), or study site employee or their close relatives

19. History of acute or chronic pancreatitis or other diseases of the pancreas

E.5 End points

E.5.1

Primary end point(s)

• Percentage change in glucose area under the curve (AUC) as measured by a standardised mixed-meal tolerance test (MMTT) from baseline (Day -1) to the end of 49 days of treatment

• Percentage change in body weight from baseline (Day 1) to the end of 49 days of treatment

E.5.1.1

Timepoint(s) of evaluation of this end point

• Baseline (Day -1) to the end of 49 days of treatment

• Baseline (Day 1) to the end of 49 days of treatment

E.5.2

Secondary end point(s)

• Change in glycated haemoglobin (HbA1c) from baseline (Day -1) to the end of 49 days of treatment

• Change in fasting plasma glucose (Day -1) from baseline to the end of 49 days of treatment

• Change in body weight (kg) from baseline (Day 1) to the end of 49 days of treatment

• Proportion of subjects achieving > 5% body weight loss from baseline (Day 1) after 49 days of treatment

• Measures of safety and tolerability (24 hour heart rate and blood pressure, other vital signs, ECG, laboratory test results, and adverse events [AEs])

• PK endpoints for 50 µg MEDI0382 after 1, 7, and 14 days of treatment and 300 µg MEDI0382 after 1 and 28 days of treatment; AUC over a dosing duration, maximum observed concentration, time to maximum observed concentration, terminal half-life, trough plasma concentration and accumulation ratio, Cmin [R0]

• Development of anti-drug antibodies (ADA) and titre (if confirmed positive)

• Percentage change in glucose AUC as measured by a standardised MMTT from baseline (Day -1) to the end of 7 days of treatment

E.5.2.1

Timepoint(s) of evaluation of this end point

• Baseline (Day -1) to the end of 49 days of treatment

• Baseline to the end of 49 days of treatment

• Baseline (Day 1) to the end of 49 days of treatment

• Baseline (Day 1) after 49 days of treatment

• Duration of study (refer to protocol schedule of events)

• After 1, 7, 14 or 28 days of treatment (refer to protocol schedule of events)

• Refer to protocol schedule of events

• Baseline (Day -1) to the end of 7 days of treatment

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

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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)

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

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

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)

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.4.2.2

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)

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

2017-08-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-08-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-01-23

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