Clinical Trials Register

Summary
EudraCT Number:	2011-003808-20
Sponsor's Protocol Code Number:	EV077/C005
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-08-22
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

Germany - BfArM

A.2

EudraCT number

2011-003808-20

A.3

Full title of the trial

A Trial Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EV-077-3201-2TBS in Healthy Subjects and Type 2 Diabetic Subjects

A.3.1

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

Study in healthy subjects and type 2 diabetic subjects to assess the safety, tolerability and pharmacokinetics of 28 days EV-077-3201-2TBS treatment, and the effects of thromboxane receptor antagonism on platelet function, vascular inflammation and vascular oxidative stress

A.4.1

Sponsor's protocol code number

EV077/C005

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	Evolva SA
B.1.3.4	Country	Switzerland
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	Evolva SA
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Evolva SA
B.5.2	Functional name of contact point	Chief Medical Officer
B.5.3	Address:
B.5.3.1	Street Address	Duggingerstrasse 23
B.5.3.2	Town/ city	Reinach
B.5.3.3	Post code	4153
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	0041614852000
B.5.5	Fax number	0041614852001
B.5.6	E-mail	info@evolva.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	EV-077-3201-2TBS
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	EV-077-3201-2TBS
D.3.9.3	Other descriptive name	EV-077-3201-2 tert-butylamine salt (TBS)
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	100
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	Aspirin N 100mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Vital GmbH
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	Aspirin N 100mg
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	50-78-2
D.3.9.3	Other descriptive name	ACETYLSALICYLIC ACID
D.3.9.4	EV Substance Code	SUB12730MIG
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	100
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	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Healthy subjects and subjects with Type 2 Diabetes

E.1.1.1

Medical condition in easily understood language

Healthy subjects and subjects with Type 2 Diabetes

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10045242
E.1.2	Term	Type II 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

1. To assess the safety and tolerability of multiple doses of EV-077-3201-2TBS over 4 weeks in healthy subjects (Part A).
2. To investigate the potential for interaction between EV-077-3201-2TBS and ASA in healthy subjects (Part B).
3. To assess the safety and tolerability of multiple doses of EV-077-3201-2TBS over 4 weeks in type 2 diabetic subjects (Part C).

E.2.2

Secondary objectives of the trial

1. To investigate the effect of multiple doses of EV-077-3201-2TBS on platelet aggregation (Part A).
2. To investigate the effect of multiple doses of EV-077-3201-2TBS on platelet function, vascular function, vascular inflammation, vascular oxidative stress, renal function and a selection of exploratory parameters and biomarkers in type 2 diabetic subjects (Part C).
3. To investigate the pharmacokinetics of multiple doses of EV-077-3201-2TBS over 4 weeks in healthy subjects (Part A) and type 2 diabetic subjects (Part C).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

All Parts (A, B and C)
1.Informed consent obtained before any trial-related activities.
2.A male with a partner of childbearing potential must only be allowed to participate if:
•he and his partner are willing to use a medically acceptable method of birth control (e.g. condom in combination with hormonal contraception or intrauterine device, or a diaphragm with spermicide) during the study and for 3 months after participation in the study, or
•he is vasectomized (> 6 months), or
•he has a sterilized partner (> 6 months), or
•he is abstinent during the study and for 3 months after participation in the study.
Parts A and B only
3.Healthy male subjects aged 18 to 50 inclusive.
4.Body weight 70 to 90 kg inclusive.
Part C only
5.Male or female subjects aged 18 to 70 years inclusive. (NB. All females must be of non-reproductive potential, i.e. post-menopausal, post-hysterectomy, bilateral tubal ligation or bilateral oophorectomy).
6.Body mass index (BMI) between 25.0 and 40.0 kg/m2 (both inclusive).
7.Subjects with type 2 diabetes mellitus according to American Diabetes Association (ADA) definition for a duration of at least 3 years, on a stable therapy with oral anti-diabetic drugs (OAD) or with insulin, with or without one or two OADs or a glucagon like peptide-1 (GLP-1) agonist, or glitazones. Stable baseline therapy is defined as unchanged dose regimen for at least 3 months before administration of the study drug.
8.HbA1c ≥ 6.0 and ≤ 9.0 %.
9.History of hyperlipidemia, with either elevated LDL cholesterol (>140 mg/dL) without therapy, or treatment with statins (NB. Patients on statin therapy must have a 2 week wash-out before they can enter the study).
10.History of hypertension, either with systolic blood pressure levels between 140 to 160 mmHg without treatment, or treatment with ACE inhibitors or ARB, which should be stable over the previous 3 months.

E.4

Principal exclusion criteria

All Parts (A, B and C)
1.Employees or personnel affiliated with the Sponsor or Investigator.
2.Previous participation (randomisation) in this trial.
3.The intake of any investigational drug within one month or five half-lives, whatever is longer, before administration of study drug.
4.A history of significant multiple drug allergies or with a known allergy to the trial product or any medicine chemically related to the trial product, as judged by the Investigator.
5.Clinically significant acute illness within 2 weeks before administration of study drug, including severe infections, as judged by the Investigator.
6.Abnormal and clinically significant ECG at screening.
7.Donation of any blood or plasma in the past month or in excess of 500 mL within the 12 weeks preceding screening.
8.Intake of paracetamol within 7 days before start of treatment.
9.Surgery or trauma with significant blood loss within the last 3 months before administration of study drug.
10.Smokers (negative cotinine test required).
11.A positive result of the human immunodeficiency virus (HIV) 1 and 2 test and/or positive Hepatitis B antigen and/or positive Hepatitis C antibody screen.
12.A history of alcoholism or drug/chemical abuse, or a positive result in the urine/ drug/ breath alcohol screen, or consumption of more than 14 units of alcohol per week (one unit of alcohol equals about 250 mL of beer or lager, one glass of wine, or 20 mL spirits).
13.Mental incapacity or language barriers which preclude adequate understanding or cooperation, unwillingness to participate in the trial, known or suspected not to comply with study directives or not to be reliable or trustworthy, or subject who in the opinion of their general practitioner or the Investigator should not participate in the trial.
14.Clinically significant abnormal laboratory test results during the screening as judged by the Investigator (one retest within a week is permitted, the last result being conclusive).
15.Increased risk of bleeding, e.g. subjects with a history of deep cerebral bleeding or known defects of hemostasis with increased risk of bleeding, as judged by the Investigator.
16.Liver enzymes (ALT and AST) more than twice the upper limit of normal.
Parts A and B only
17.Any history of or presence of clinically significant diseases such as cancer, clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, haematological, dermatological, venereal, neurological, psychiatric diseases, other major disorders as judged by the Investigator.
18.Supine blood pressure at screening, after resting for 5 min, of > 140 mmHg systolic or > 90 mmHg diastolic (excluding white-coat hypertension; therefore, if a repeat measurement on a second screening visit shows values within the range, the subject can be included in the trial).
19.Intake of anti-inflammatory drugs, OTC drugs or herbal remedies within 14 days before start of treatment. Steroid therapy other than topical application is not allowed.
Part C only
20.History of or presence of clinically significant diseases such as cancer, clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, haematological, dermatological, venereal, neurological, psychiatric diseases, other major disorders as judged by the Investigator, or significant secondary diabetic complications, such as but not limited to clinically relevant peripheral neuropathy, retinopathy, diabetic foot ulcers, as judged by the Investigator.
21.Supine blood pressure at screening, after resting for 5 min, of > 160 mmHg systolic or > 95 mmHg diastolic (excluding white-coat hypertension; therefore, if a repeat measurement on a second screening visit shows values within the range, the subject can be included in the trial).
22.Type 1 diabetes mellitus.
23.Intake of anti-inflammatory drugs including ASA within 14 days before start of treatment. Steroid therapy other than topical application is not allowed.
24.Any treatment with diuretics (hydrochlorothiazides are allowed).

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

End of the study.

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

End of the 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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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

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

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

Last Subject Last Visit

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

E.8.9.2

In all countries concerned by the trial 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

Yes

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)

There is no need for for treatment or extra care after the subject has ended the participation in the trial.

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

2011-10-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-10-05

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2012-05-22

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