Clinical Trials Register

Summary
EudraCT Number:	2012-000972-40
Sponsor's Protocol Code Number:	MK-6621-055
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-05-31
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2012-000972-40

A.3

Full title of the trial

A Multicentered, Randomized, Open-Label, Pragmatic Use Study Comparing Vernakalant Therapy to Amiodarone Therapy in Acute Management of Recent Onset Atrial Fibrillation.

A.3.1

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

Study Comparing Pragmatic Use of Vernakalant and Amiodarone Treatments in the Emergency Room Management of Patients with Recent Onset Atrial Fibrillation.

A.3.2

Name or abbreviated title of the trial where available

Vernakalant vs.Amiodarone Comparative Effectiveness Trial

A.4.1

Sponsor's protocol code number

MK-6621-055

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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.1.3.4	Country	United States
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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.5.2	Functional name of contact point	Sarah Camp
B.5.3	Address:
B.5.3.1	Street Address	P.O. Box 100 Whitehouse Station
B.5.3.2	Town/ city	One Merck Drive
B.5.3.3	Post code	NJ 08889-0100
B.5.3.4	Country	United States
B.5.4	Telephone number	+1 732 594 4342
B.5.5	Fax number	+1 732 594 4343
B.5.6	E-mail	sarah_camp@merck.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	BRINAVESS 20 mg/ml, concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	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	Vernakalant Hydrochloride
D.3.9.1	CAS number	748810-28-8
D.3.9.2	Current sponsor code	MK-6621
D.3.9.3	Other descriptive name	VERNAKALANT HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB30707
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	20
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	Comparator
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	AMIODARONE 150 mg i.v Carino injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Carinopharm 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.3.4	Pharmaceutical form	Concentrate for solution for injection
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	AMIODARONE HYDROCHLORIDE
D.3.9.1	CAS number	19774-82-4
D.3.9.4	EV Substance Code	SUB00472MIG
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	50
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

Atrial Fibrilation

E.1.1.1

Medical condition in easily understood language

Cardiac dysrhythmia

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	15.0
E.1.2	Level	LLT
E.1.2	Classification code	10007545
E.1.2	Term	Cardiac dysrhythmias
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

To determine whether the primary use of vernakalant results in a higher proportion of patients discharged from the ER to home, home-equivalent, or LTCF within 12 hours from randomization compared to the primary use of amiodarone in patients with recent onset AF (current episode ≤7 days) who present for rapid conversion.

E.2.2

Secondary objectives of the trial

Objective 1: To determine whether the primary use of vernakalant reduces the proportion of patients admitted to a hospital (acute care, intensive care, or any other unit with a higher level of care than the ER) from the ER compared to primary use of amiodarone for rapid conversion of recent onset AF (current episode ≤7 days) in the ER.
Objective 2: To assess the safety of a primary vernakalant approach compared to a primary amiodarone approach for acute cardioversion in patients with recent onset AF (current episode ≤7 days).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Symptomatic AF (duration of current episode is ≤7 days), is hemodynamically stable,
and has no other condition at the time of screening that may result in acute hospitalization. The treating physician has determined that the patient is eligible for
acute cardioversion and no additional diagnostic evaluation is required that may delay cardioversion.
2. Non-surgery adult patient with AF, duration of current episode ≤ 7 days
3. Documented AF by ECG.
4. Understanding of the study procedures and has given informed consent.
5. If the patient is female and of reproductive potential, the patient agrees to remain
abstinent or use 2 acceptable methods of birth control from time of screening until
30-day follow-up. Acceptable methods of birth control are: intrauterine device,diaphragm with spermicide, contraceptive sponge, condom, partner vasectomy, hormonal contraception.
6. Weighing at least 45 kg.
7. Receiving adequate anticoagulant therapy as defined by the clinical practice of the
Investigator. If the investigator believes that the patient does not need anticoagulant
therapy, it is acceptable.

E.4

Principal exclusion criteria

1. Hypersensitivity to the vernakalant or amiodarone or to citric acid, sodium chloride,
sodium hydroxide, or iodine.
2. Severe aortic stenosis.
3. Systolic blood pressure <100 mmHg.
4. Heart failure class NYHA III and NYHA IV, or previously documented LVEF ≤ 35%.
5. Prolonged QT (uncorrected > 440 msec) on screening ECG.
6. Severe bradycardia, sinus node dysfunction, or second and third degree heart block in
the absence of a pacemaker.
7. Use of intravenous rhythm control anti-arrhythmics (class I and III) within 4 hours of
study drug administration.
8. Acute coronary syndrome (including myocardial infarction) within the last 30 days.
9. Evidence of history of thyroid dysfunction, as determined by the investigator.
10. Severe acute respiratory failure or cardiovascular collapse.
11. Currently using any medications known to prolong the QT interval, including but not
limited to: erythromycin, co-timoxazole, pentadine injection, chlorpromazine,
thioridazine, pimozide, haloperidol, lithium, tri-cyclic antidepressants (e.g. doxepin,
maprotiline, and amitriptyline, terfenadine, astmemizole, and anti-malarial agents
(e.g. quinine, mefloquine, chloroquine, and halofantrine).
12. Currently participating in another drug study or has received an investigational drug
within 30 days prior to enrollment.
13. Pregnant (positive serum β-HCG) or breast-feeding, or expecting to conceive from
time of screening until 30-day follow-up.
14. Any condition or situation which, in the opinion of the investigator, might pose a risk
to the patient or interfere with participation in the study.
15. Any occurrence of atrial flutter (AFL) at screening.
16. Complex ventricular ectopy (i.e., idioventricular rhythm, accelerated idioventricular
rhythm, sustained or unsustained ventricular tachycardia, ventricular fibrillation,
Torsades de Pointes, ventricular flutter, or frequent polymorphic premature ventricular complexes) on any ECG or on heart monitoring during screening or at baseline.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the proportion of patients discharged from the ER to home, home-equivalent, or LTCF within 12 hours from randomization. Patients who withdraw after infusion of any amount of study medication prior to observing the endpoint will have a response of not discharged imputed for the primary endpoint.

E.5.1.1

Timepoint(s) of evaluation of this end point

Within 12 hours from randomization.

E.5.2

Secondary end point(s)

The secondary efficacy endpoint is the overall hospitalization rate, which is calculated as
the proportion of patients admitted to hospital directly from the ER after randomization.

E.5.2.1

Timepoint(s) of evaluation of this end point

After randomization during study period.

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

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

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Brazil

France

Italy

Portugal

E.8.7

Trial has a data monitoring committee

Yes

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

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:

440

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

430

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

Yes

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

120

F.4.2

For a multinational trial

F.4.2.1

In the EEA

710

F.4.2.2

In the whole clinical trial

870

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)

NAP

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

2012-06-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-08-20

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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IMP with orphan designation in the indication
Orphan Designation Number:
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