Clinical Trials Register

Summary
EudraCT Number:	2014-003963-39
Sponsor's Protocol Code Number:	CV185-066
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2014-10-02
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2014-003963-39

A.3

Full title of the trial

An In Vitro Comparison of Apixaban Activity in Adult and Pediatric Plasma

A.3.1

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

A blood collection in healthy adults and children aiming to see if apixaban, a new investigational anticoagulant (blood thinner) currently studied in adults, can also be used in children.

A.4.1

Sponsor's protocol code number

CV185-066

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	Bristol-Myers Squibb Company
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	Bristol-Myers Squibb Company
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	Bristol-Myers Squibb Company
B.5.2	Functional name of contact point	CTT group Manager
B.5.3	Address:
B.5.3.1	Street Address	Route 206 and Province Line Road
B.5.3.2	Town/ city	Lawrenceville
B.5.3.3	Post code	NJ 08543
B.5.3.4	Country	United States
B.5.6	E-mail	ctt.group@bms.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	Eliquis
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Company & Pfizer Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Film-coated 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.3.8	INN - Proposed INN	APIXABAN
D.3.9.1	CAS number	503612-47-3
D.3.9.2	Current sponsor code	BMS-562247-01
D.3.9.4	EV Substance Code	SUB25425
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	2.5
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	Eliquis
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Company & Pfizer Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Film-coated 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.3.8	INN - Proposed INN	APIXABAN
D.3.9.1	CAS number	503612-47-3
D.3.9.2	Current sponsor code	BMS-562247-01
D.3.9.4	EV Substance Code	SUB25425
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	5
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

Thrombosis

E.1.1.1

Medical condition in easily understood language

Thrombosis

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	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10066899
E.1.2	Term	Venous thromboembolism
E.1.2	System Organ Class	100000004866

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 characterize the in vitro anti-FXa activity of apixaban in pediatric subjects as compared to adult population using Rotachrom chromageneic anti-Xa assay.

E.2.2

Secondary objectives of the trial

- To characterize the in vitro anti-FXa activity of apixaban in pediatric populations as ompared to adult population using Diapharma RVV anti-Xa assay.
- To characterize modified Prothrombin Time in pediatric populations as compared to adult population.
- To characterize Factor X level in pediatric populations as compared to adult population using Diapharma RVV assay.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

* For healthy adult subjects:
- signed informed consent form
- Male or female subjects as determined by no clinically significant deviation from normal in medical history and physical examination
- ages 18 to 45

* For pediatric patients:
- Parent or legally acceptable representatives must sign informed consent form for all subjects < 18 years old. Assent should be obtained when the minor is judged to be of an age of reason (see protocol Appendix 1).
- signed informed consent form from the mother donating the umbilical cord blood.
- Male and female subjects as determined by no clinically significant findings in medical history or physical examination that would prevent the subjects from donating 1-9 mL of blood.

E.4

Principal exclusion criteria

* For healthy adult subjects:
(1) Medical History and Concurrent Diseases
a) Any significant acute or chronic medical illness.
b) Any major surgery within 4 weeks of enrollment
c) History or evidence of abnormal bleeding or coagulation disorder and/or having a first degree relative coagulation disorder due to genetic defects.
d) Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of study enrollment.
e) Blood transfusion within 4 weeks of study enrollment.
f) Inability to be phlebotomized and/or tolerate venous access.
g) Recent (within 6 months) drug or alcohol abuse
h) Any other sound medical, psychiatric and/or social reason as determined by the investigator.
i) Smoking more than 10 cigarettes per day.
j) History of positive urine screen for drugs of abuse in the past 6 months.
k) PMH of positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV viral RNA or HIV-1, -2 antibody.
(2) Physical Findings
a) Evidence of excessive bruising, petechia, or organ dysfunction or clinically significant findings that would prevent donation of blood.
(3) Prohibited Treatments and/or Therapies
a) Exposure to any investigational drug or placebo within 4 weeks of enrollment.
b) Use of any other drugs, including over-the-counter medications and herbal preparations, within 1 week prior to study enrollment.
c) Currently or within 14 days of blood draw taking any anticoagulants, and thrombolytics
(4) Other Exclusion Criteria
Prisoners or subjects who are involuntarily incarcerated; Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness

* For pediatric patients:
(1) Medical History and Concurrent Diseases
a) Any significant acute medical illness or a chronic medical illness of leukemia, lymphoma, hepatic impairment, significant renal impairment or severe anemia.
b) Subjects known to have prolongation of PT or PTT.
c) History of positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV viral RNA or HIV-1, -2 antibody. Pediatric subjects born to HIV, hepatitis B, hepatitis C positive mothers may be included into the study
if they test positive on an antibody test, but they are confirmed not HIV, HCV, or HBV infected after been tested according to standard of care guidelines.
d) Subjects with cancer on any therapy or subjects in remission treated with chemotherapy < 3 months ago.
e) Subjects with known genetic disorders such as hemophilia or thrombophilia or other factor deficiencies.
f) History or evidence of abnormal bleeding or coagulation disorder and/or having a first degree relative coagulation disorder due to genetic defects.
g) Any major surgery within 4 weeks of study enrollment
h) Blood transfusion within 4 weeks of study enrollment.
i) Twenty-four hour blood volume loss ≥ 3% of subject’s estimated blood volume.
j) Inability to be phlebotomized and/or tolerate venous access.
k) Recent (within 6 months) drug or alcohol abuse
l) Any other medical, psychiatric and/or social reason as determined by the investigator.
m) Smoking more than 10 cigarettes per day.
n) History of a significant complicated pregnancy as determined by PI or designee (for women donating umbilical cord blood).
o) Pediatric subjects <1 year of age with maternal history of lupus anticoagulant, ITP, or other acquired coagulopathy.
(2) Physical Findings
a) Evidence of excessive bruising, petechia, or organ dysfunction or clinically significant findings that would prevent donation of blood.
b) For neonates, birth weight < 2500gm
(3) Prohibited Treatments and/or Therapies
a) Exposure to any investigational drug or placebo within 4 weeks of study drug administration.
b) Currently or within 14 days of blood draw taking any anticoagulants and thrombolytics
(4) Other Exclusion Criteria
Prisoners or subjects who are involuntarily incarcerated; Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness

E.5 End points

E.5.1

Primary end point(s)

There are no clinical endpoints for this study (In vitro analysis).
Pharmacodynamic Endpoint: In vitro analysis of Rotachrom anti-Xa activity, Diapharma factor X level and anti-Xa
activity, modified Prothrombin Time, and other exploratory clotting assays or coagulation biomarkers if applicable.
Safety assessments will be limited to routine clinical assessment following the blood draw.

E.5.1.1

Timepoint(s) of evaluation of this end point

See above, in vitro analysis.

E.5.2

Secondary end point(s)

See above, in vitro analysis.

E.5.2.1

Timepoint(s) of evaluation of this end point

See above, in vitro analysis.

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

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Non-therapeutic, in vitro PD study

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Information not present in EudraCT

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

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

United States

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.8.9.2

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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.3.1

Number of subjects for this age range:

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

Yes

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2014-10-02.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

Yes

F.3.3.4

Nursing women

Yes

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

- Parent or legally acceptable representatives must sign informed consent form for all subjects < 18
- Assent should be obtained when the minor is judged to be of an age of reason (see Appendix 1).

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Signed informed consent form from mother donating the umbilical cord blood

F.4 Planned number of subjects to be included

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)

None

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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