Clinical Trials Register

Summary
EudraCT Number:	2015-001452-30
Sponsor's Protocol Code Number:	010815testis
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-09-17
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

Denmark - DHMA

A.2

EudraCT number

2015-001452-30

A.3

Full title of the trial

A Randomized double-blind study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig Cell Insufficiency (Einstein-intervention)

Randomiseret, dobbeltblindet forsøg med testosteronsubstitution eller
placebo til mænd, tidligere behandlet for testikelkræft, med let Leydig celle
insufficiens (Einstein-intervention)

A.3.1

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

A randomized double-blind study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig Cell Insufficiency (Einstein-invervention)

Randomiseret, dobbeltblindet forsøg med testosteronsubstitution eller
placebo til mænd, tidligere behandlet for testikelkræft, med let Leydig celle
insufficiens

A.3.2

Name or abbreviated title of the trial where available

EINSTEIN INTERVENTION

A.4.1

Sponsor's protocol code number

010815testis

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	Copenhagen University Hospital Rigshospitalet
B.1.3.4	Country	Denmark
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	Danish Cancer Society
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Copenhagen University Hospital Rigshospitalet
B.5.2	Functional name of contact point	Clinical Research Unit Information
B.5.3	Address:
B.5.3.1	Street Address	Blegdamsvej 9
B.5.3.2	Town/ city	Copenhagen East
B.5.3.3	Post code	2100
B.5.3.4	Country	Denmark
B.5.6	E-mail	mikkel.bandak@regionh.dk

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	Tostran
D.2.1.1.2	Name of the Marketing Authorisation holder	ProStrakan Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Tostran
D.3.2	Product code	G03BA03
D.3.4	Pharmaceutical form	Transdermal gel
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TESTOSTERONE
D.3.9.1	CAS number	58-22-0
D.3.9.4	EV Substance Code	SUB10937MIG
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	10 mg to 40 mg
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	Gel
D.8.4	Route of administration of the placebo	Transdermal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Leydig Cell dysfunction

Leydig celle insufficiens

E.1.1.1

Medical condition in easily understood language

Borderline low levels of testosterone in testicular cancer survivors

Grænselavt niveau af mandligt kønshormon hos mænd, der tidligere er
behandlet for testikelkræft

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10067734
E.1.2	Term	Testosterone deficiency
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

Investigation of changes in insulin sensitivity after 12 months treatment with testosterone substitution

Undersøgelse af ændring i insulinsensitivitet efter 12 måneders behandling med testosterone substitution

E.2.2

Secondary objectives of the trial

Prevalence of Metabolic Syndrome, body compostion, systemic inflammation, symptoms of testosterone deficiency

Forekomst af Metabolisk Syndrom, kropssammensætning, systemisk inflammation og symptomer på testosteronmangel.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Signed informed consent.
Previous treatment for testicular cancer.
No signs of relapse 1 year after last treatment (orchiectomy, radiotherapy, chemotherapy).
Free testosterone < the age-adjusted median and > -2 standard deviations (SD) from the age-adjusted median and LH > 2 SD from the age-adjusted median.
Age > 18 years and <65 years.

Underskrevet informeret samtykke.
Tidligere behandling for testikelkræft (germinalcellecancer).
Intet tegn på tilbagefald 1 år efter seneste behandling (orkiektomi, strålebehandling, kemoterapi).
Frit testosteron < den alderskorrigerede median og > -2 standarddeviationer (SD) fra den alderskorrigerede median samt LH > 2 SD fra den alderskorrigerede median.
Alder > 18 år og <65 år.

E.4

Principal exclusion criteria

Paternity wish at the time of inclusion*
Treatment with testosterone within the last 6 months.
Contraindications to testosterone treatment (prostate cancer, prostate specific antigen (PSA)> 4 microg/L), malignancy suspect prostate by digital rectal examination, Alanine aminotransferase (ALT)> 1.5 upper reference level, Erythrocyte Volume Fraction (EVF) > 50%.
Breast cancer.
Symptomatic obstructive sleep apnoea syndrome
Heart failure > NYHA II.
Uncontrolled hypertension: (Systolic blood pressure > 160 mm Hg despite antihypertensive treatment, measured at two separate occasions)
Inability to understand information about the trial
Participation in any other clinical trial
Allergy for the active substance

Behandling med testosteron inden for de seneste 6 måneder.
Kontraindikationer for testosteronbehandling (prostatacancer, prostata specific antigen (PSA) > 4 microg/L), malignitets suspekt prostata ved rektal eksploration, Alanin aminotransferase (ALAT) > 1.5 øvre referenceområde, hæmatokrit >50%).
Brystcancer.
Symptomgivende obstruktiv søvnapnø.
Hjertesvigt > NYHA II.
Ukontrolleret hypertension.
Anden lidelse, som gør, at forsøgsansvarlige ikke skønner, at deltagelse er gennemførlig (psykisk sygdom, stofmisbrug etc.).
Manglende evne til at forstå information om forsøget.
Samtidig deltagelse i andet klinisk forsøg.

E.5 End points

E.5.1

Primary end point(s)

Insulin sensitivity (evaluated by Oral Glucose Tolerance Test)

Insulinsensitivitet (målt ved oral glucose tolerans test (OGTT)).

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluated at baseline and after 26 weeks and 52 weeks of treatment and 3 months after end of study

Evalueres ved baseline og efter 26 ugers behandling og 52 ugers behandling og 3 måneder efter end-of-study

E.5.2

Secondary end point(s)

Metabolic Syndrome (International Diabetes Federation Criteria).
Body composition and bone mineral density (Dual energy X-ray absorptiometry (DXA-scan)).
Systemic inflammation
Plasma -adipocytokines
Fasting plasma-glucose, plasma-insulin, (homeostatic model assessment-index (HOMA-index)), haemoglobin A1c.
Fasting plasma-lipids
Quality of life (EORTC-QLQ-30-questionnaire)

Metabolisk syndrom (International Diabetes Federation kriterier).
Kropssammensætning og knogletæthed (Dual energy X-ray absorptiometry (DXA-scan)).
Systemisk inflammation
Plasma adipocytokiner
Faste plasma-blodsukker, plasma-insulin, (homeostatic model assessment-index (HOMA-index)), hæmoglobin A1c.
Faste plasma-lipider
Livskvalitet (EORTC-QLQ-30-spørgeskema)

E.5.2.1

Timepoint(s) of evaluation of this end point

Evaluated at baseline and after 26 weeks and 52 weeks of treatment and 3 months after end of study

Evalueres ved baseline og efter 26 ugers behandling og 52 ugers behandling og 3 måneder efter end-of-study

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)

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

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

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

3 months after last participants last visit

3 måneders efter sidste forsøgspersons sidste besøg

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

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

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)

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

2015-12-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-08-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-06-05

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