Clinical Trials Register

Summary
EudraCT Number:	2011-006114-14
Sponsor's Protocol Code Number:	62326B1658
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2012-04-02
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

UK - MHRA

A.2

EudraCT number

2011-006114-14

A.3

Full title of the trial

“Effects of testosterone on glycaemic control and other Cardiovascular Risk factors in Hypogonadal Men with uncontrolled Type 2 Diabetes: A randomized double – blinded placebo controlled add on trial using depot testosterone undecanoate”

A.3.1

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

Effects of tesstosterone( male hormone) on glucose control and cardiovascular risk factors in men with type 2 diabetes

A.3.2

Name or abbreviated title of the trial where available

Testosterone and glycaemic control in hypogonadal men. Version 1

A.4.1

Sponsor's protocol code number

62326B1658

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	Research and Development department
B.1.3.4	Country	United Kingdom
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	Barnsley Research & Development
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	Research & Development Dept. Barnsley Hospital NHSFT
B.5.2	Functional name of contact point	Michael Bramall
B.5.3	Address:
B.5.3.1	Street Address	Block 14, BHNFT, Gawber Road
B.5.3.2	Town/ city	Barnsley
B.5.3.3	Post code	S75 2EP
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01226432348
B.5.5	Fax number	01226435075
B.5.6	E-mail	michael.bramall@nhs.net

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	Nebido
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer plc
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Nebido
D.3.2	Product code	not applicable
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Testosterone Undecanoate
D.3.9.2	Current sponsor code	6232 6B1658
D.3.9.3	Other descriptive name	17beta-Hydroxyandrost-4-en-3-one
D.3.9.4	EV Substance Code	AS1
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	1000
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	Injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Hypogonadism
Type 2 Diabetes
Cardiovascular risk

E.1.1.1

Medical condition in easily understood language

Deficiency of the male hormone
Type 2 Diabetes
Heart problems

E.1.1.2

Therapeutic area

Body processes [G] - Metabolic Phenomena [G03]

MedDRA Classification

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 purpose of this study is to find out the effect of adding testosterone to the standard diabetes treatment on glucose control. The primary outcome of the study will be HbA1C ( a blood test which looks at the average blood glucose control in patients with diabetes)and fasting plasma blood sugar levels.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Men with age >18 years
2. Type 2 Diabetes mellitus
3. HbA1C >7% <9.5%
4. Confirmed hypogonadism (early morning [0800−1000 h] total testosterone [TT] ≤12 nmol/L or calculated free testosterone ≤255 pmol/L on two occasions ≥1 week apart), with at least two symptoms of hypogonadism
5. Must be naïve to androgen replacement therapy
6. If on replacement therapy for the hypopituitarism or multiple endocrine deficiencies, the subject must be on stable doses of thyroid hormone and adrenal replacement hormones for at least 14 days prior to the enrolment.
7. No contraindication to the use of the study product – testosterone undecanoate
8. Patients understands the study protocol and voluntarily agrees to participate by providing written informed consent

E.4

Principal exclusion criteria

1. Inability to give informed consent
2. Polycythaemia/ Haematocrit of >0.52
3. Abnormal prostrate digital rectal examination( palpable nodule/s) or severe prostratism or elevated PSA
4. History of prostrate cancer or breast cancer
5. Patient is enrolled in another experimental trial which involves the use of an investigational drug or device, or an intervention that would interfere with the conduct of the trial
6. Patients with significant intercurrent disease like severe heart failure, kidney disease on dialysis, psychiatric illness or any other co-morbidities making them unable to attend the scheduled visits of the trial
7. History of alcohol abuse or any drug abuse in the past 2 years
8. Current use of antiandrogens, glucocorticoids ( except where used as replacement therapy), long acting opioid analgaesics( eg., methadone, buprenorphine), oestrogens, CYP3A4 inducers( eg., barbiturates) CYP3A4 inhibitors (eg., HIV antivirals, amiodarone, ketaconazole, ciprofloxacin, azithromycin etc)
9. Men seeking to father a child and have not yet completed the family.

E.5 End points

E.5.1

Primary end point(s)

HbA1c

E.5.1.1

Timepoint(s) of evaluation of this end point

0,12,24,36,52 weeks

E.5.2

Secondary end point(s)

To compare the impact of testosterone therapy on

I. Body composition ( measuring the body fat and lean muscle mass)

a) Waist circumference and waist hip ratio
b) Body mass index
c) Percentage body fat (by Tanita body fat analyzer)
d) Body composition using DEXA scan

II. Insulin resistance

a) Homa – IR (Homeostatic Model of Assessment of Insulin Resistance) in patients not on insulin (three blood samples for fasting insulin samples taken 5 minutes apart with fasting glucose)

III. Lipid Profile ( cholesterol and other fat in blood)

Fasting lipid profile (total cholesterol, LDL Cholesterol, HDL- Cholesterol, Triglycerides, Lipoprotein a and ApoE)

IV. Inflammation

hsCRP, IL-6, IL6 Soluble receptor, Adiponectin, leptin, TNF alpha, IL- 10, IL-1beta, ICAM – 1, VCAM -1 and AGEs (advance glycation end products).
We also intend to store blood at -70oC for later analysis.

V. Macrophage function: ( function of the scavenger cell in the blood which play a inportant role in the development of plaque in the arteries causing heart disease)

-Monocyte RNA: qPCR on specific genes involved in lipid, cholesterol, glucose metabolism and inflammation

-Primary cell culture of macrophages for further assessment of these pathways – effect of exogenous testosterone and LXR agonists and antagonists on gene expression (qPCR) and protein level (Western blotting with densitometry)

VI. Blood pressure

After rest, 2 readings 5 minutes apart.
24 hr BP monitor

VII. Renal(kidney)and Liver Function

Urinary microalbumin, serum urea, creatinine and eGFR.
Standard liver function tests (ALT, AST, alkaline phosphatase and gamma GT).

VIII. Carotid Intima-Media Thickness ( measuring the thickness of carotid artery) (using Sonosite Portable Ultrasound device)

IX. DNA collection: ( optional) ( looking at the genetic code of a cell)

To look at androgen-receptor polymorphisms and its association with the above variables

X. Safety

Prostrate Specific Antigen, Haemoglobin, haematocrit

XI. Questionnaires

ADDQoL
AMS (Aging Male Symptom Score)
IIEF (International Index of Erectile Dysfunction)
SF36 –Quality of life Questionnaire
Mini mental score
Validation of a new questionnaire for hypogonadism in diabetes

E.5.2.1

Timepoint(s) of evaluation of this end point

0,12,24,36,52 weeks.

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

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)

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

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Phase 1: Randomised double blinded placebo controlled trial. Phase 2 : open labelled.

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

Last visit of the last subject will be the end of the trial.

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