Clinical Trials Register

Summary
EudraCT Number:	2016-003521-42
Sponsor's Protocol Code Number:	ARG-E08
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:	2016-11-25
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2016-003521-42

A.3

Full title of the trial

SAICoDis – Safety of Argatroban Infusion in Conduction Disturbances. A prospective, open, multicenter safety study to investigate conduction disturbances in patients receiving argatroban therapy.

A.3.1

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

Investigation of the influence of the antithrombic agent argatroban on the electric conduction in the heart.

A.3.2

Name or abbreviated title of the trial where available

SAICoDis

A.4.1

Sponsor's protocol code number

ARG-E08

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	Mitsubishi Tanabe Pharma GmbH
B.1.3.4	Country	Germany
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	Mitsubishi Tanabe Pharma GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Mitsubishi Tanabe Pharma Europe Ltd
B.5.2	Functional name of contact point	General Information
B.5.3	Address:
B.5.3.1	Street Address	Dashwood House, 69 Old Broad Street
B.5.3.2	Town/ city	London
B.5.3.3	Post code	EC2M 1QS
B.5.3.4	Country	United Kingdom
B.5.6	E-mail	regulatory@mt-pharma-eu.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	Yes
D.2.1.1.1	Trade name	Argatra Multidose
D.2.1.1.2	Name of the Marketing Authorisation holder	Mitsubishi Tanabe Pharma 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	Not applicable (since trade name exist)
D.3.2	Product code	Not applicable (since trade name exist)
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Argatroban-monohydrat
D.3.9.1	CAS number	141396-28-3
D.3.9.2	Current sponsor code	ARG
D.3.9.3	Other descriptive name	ARGATROBAN MONOHYDRATE
D.3.9.4	EV Substance Code	SUB48842
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients without diagnosed HIT II but with a coronary heart disease and with a diagnosed stable or unstable angina are planned for a percutaneous coronary intervention (PCI) according to clinical routine. Patients undergoing an elective PCI require an antithromotic therapy. In this trial argatroban will be used for parenteral antithrombotic therapy of adult patients undergoing a routine PCI. The influence of argatroban on QT interval will be investigated during the PCI-related treatment.

E.1.1.1

Medical condition in easily understood language

Patient with arteriosclerosis of coronary vessels are routinely planned for a coronary intervention to wide narrowed vessels. To avoid blood coagulation during PCI argatroban will be used.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

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	10003211
E.1.2	Term	Arteriosclerosis coronary artery
E.1.2	System Organ Class	10007541 - Cardiac 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 determine change of QTc interval during intravenous argatroban infusion in patients undergoing PCI. To observe whether argatroban has a pharmacological effect on cardiac repolarization, it will be investigated, if a mean QTc prolongation of more than 10 ms will occur between ECG-2 (ECG immediately after cardiac intervention when patient is fully anticoagulated with argatroban) and ECG-1 (baseline ECG).

E.2.2

Secondary objectives of the trial

- Determination of the QTc interval after sufficient wash-out period by ECG-3 which needs to be performed > 8 but ≤ 28 hours after termination of prolonged argatroban infusion.
- Investigation of dependence of QTc interval on gender and applied doses.
- Determination of coagulation status during argatroban therapy.
- Assessment of safety-related events within the scope of anticoagulation with argatroban, for example bleeding events or thomboembolic events.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The patient is at least 18 years of age; Patient is willing to give written informed consent and willingness to participate and to comply with the requirements of the study protocol; Patient with diagnosed stable or unstable angina (troponin negative); Patient requires elective percutaneous coronary angioplasty or stent insertion with an approved device in one or more de novo-treated or re-stenotic lesions in native vessels, Baseline ECG without changes that impair assessment of QTc interval, Patient is on adequate platelet inhibition therapy after receiving a loading dose with ASA and clopidogrel before start of intervention.

E.4

Principal exclusion criteria

Patient is pregnant or nursing, participation in another clinical trials within last 3 months prior to study start; any condition contraindicates the use of argatroban; marked baseline prolongation of QTc interval at baseline ECG; known intraventricular conduction disturbance; use of concomitant medications that interfere with the QTc interval; intake of digitalis within the last 2 weeks before study start; acute myocardial infarction or troponin-positive unstable angina; known hepatic disorder and renal insufficiency; intake of heparin and aPTT ≥ 35 s at screening; intake of direct oral anticoagulants; intake of anticoagulants of vitamin K antagonists and INR >1.2 at screening.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this study is the mean difference in QTc interval between ECG-2 and ECG-1.

E.5.1.1

Timepoint(s) of evaluation of this end point

QT interval of ECG-1 will be measured at screening visit which takes place up to 72 to 12h before treatment visit. Evaluation of QT interval at
ECG-2 is intended immediately after PCI at the end of treatment visit. Thus, the evaluation of primary endpoint is possible as soon as QT data and heart rate of ECG-2 are available.

E.5.2

Secondary end point(s)

Mean difference in QTc interval between ECG-3 (ECG > 8 but ≤ 28 hours after termination of prolonged argatroban infusion) and ECG-1.
Proportion of patients with a prolongation of QTc interval to > 500 ms at ECG-2.
Proportion of patients with a prolongation of QTc interval to > 500 ms at ECG-3.
Proportion of patients with a prolongation of QTc interval of > 60 ms at ECG-2 compared to ECG-1.
Proportion of patients with a prolongation of QTc interval of > 60 ms at ECG-3 compared to ECG-1.
Incidence of haemorrhagic events according to the definition of CABG-related bleeding.
Incidence of adverse events.

E.5.2.1

Timepoint(s) of evaluation of this end point

The endpoints related to proportion of patients with QT interval prolongation at ECG-2 can be evaluated after ECG-2 which is at the end of the treatment visit. Endpoints related to proportion of patients with prolonged QT interval at ECG-3 can be evaluated directly after ECG-3 as soon as the measured QT interval is available. ECG-3 is planned > 8 but ≤ 28 hours after termination of prolonged argatroban infusion.
The incidence of haemorrhagic events including adverse events will be assessed from study start (date of treatment visit) until 28 days after study termination at the latest. Thus, this endpoint can be evaluated as soon as the AE follow-up phase is finished.

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

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

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)

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

F.3.3.1

Women of childbearing potential not using contraception