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Clinical Trial Details (PDF Generation Date :- Sun, 21 Feb 2021 06:02:40 GMT)

CTRI Number CTRI/2018/01/011249 [Registered on: 10/01/2018] - Trial Registered Prospectively

Last Modified On 13/05/2020
Post Graduate Thesis No
Type of Trial Interventional
Type of Study Drug
Study Design Randomized, Parallel Group, Active Controlled Trial
Public Title of Study A large study in kids from birth to 18 years of age that have a clot in their lungs, limbs, to test a new
drug (edoxaban) compared to current drugs used for treatment and to prevent further clots in your
body
Scientific Title of A Phase 3, Open-Label, Randomized, Multicenter, Controlled Trial To Evaluate The
Study Pharmacokinetics And Pharmacodynamics Of Edoxaban And To Compare The Efficacy And Safety
Of Edoxaban With Standard Of Care Anticoagulant Therapy In Pediatric Subjects From Birth To
Less Than 18 Years Of Age With Confirmed Venous Thromboembolism (VTE)
Secondary IDs if Any Secondary ID Identifier
DU176b-D-U312 Protocol Version 3.0, IN1 Protocol Number
dated 16-AUG-2019
Details of Principal Details of Principal Investigator
Investigator or overall
Name
Trial Coordinator
(multi-center study) Designation
Affiliation
Address

Phone
Fax
Email
Details Contact Details Contact Person (Scientific Query)
Person (Scientific
Name Suneela Thatte
Query)
Designation Vice-President- Global Operations
Affiliation IQVIA RDS (India) Private Limited
Address Natraj by Rustomjee 6th Floor, 194 MV Road, Near Western Express
Highway Metro Station Andheri East, Mumbai 400 069
Mumbai
MAHARASHTRA
400069
India
Phone 912266774242
Fax 912266774343
Email [email protected]
Details Contact Details Contact Person (Public Query)
Person (Public Query)
Name Suneela Thatte
Designation Vice-President- Global Operations
Affiliation IQVIA RDS (India) Private Limited
Address Natraj by Rustomjee 6th Floor, 194 MV Road, Near Western Express
Highway Metro Station Andheri East, Mumbai 400 069
Mumbai
MAHARASHTRA
400069

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India
Phone 912266774242
Fax 912266774343
Email [email protected]
Source of Monetary or Source of Monetary or Material Support
Material Support
> Daiichi Sankyo, Inc. 399 Thornall Street Edison, NJ 08837 United States
Primary Sponsor Primary Sponsor Details
Name Daiichi Sankyo Inc
Address 399 Thornall Street Edison, NJ 08837 United States
Type of Sponsor Pharmaceutical industry-Global
Details of Secondary Name Address
Sponsor
Quintiles Research India Pvt Ltd 2nd Floor, Etamin Block, Prestige Technology
Park II Sarjapur-Marathahalli Outer Ring Road,
Bangalore-560103 Karnataka
Countries of List of Countries
Recruitment
Argentina
Brazil
Bulgaria
Canada
Chile
Croatia
Czech Republic
Denmark
Egypt
France
Germany
Hungary
India
Israel
Italy
Kenya
Lebanon
Malaysia
Mexico
Netherlands
Norway
Poland
Portugal
Republic of Korea
Romania
Russian Federation
Serbia
Singapore
Slovenia
Spain
Taiwan
Thailand

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Turkey
Ukraine
United States of America
Sites of Study Name of Principal Name of Site Site Address Phone/Fax/Email
Investigator
Dr Somashekhar H M Patel Center for Dept: Paediatrics 919825087842
Nimbalkar Medical Care & Ground floor Shree 912692222493
Education, Krishna Hospital, Gokal somashekharn@charut
Nagar, Karamsad- arhealth.org
388325, Gujarat, India.
Anand
GUJARAT
Dr Suresh Kalkunte Bhagwan Mahaveer Jain institute of vascular 9845055494
Jain Hospital sciences, Ground Floor 080222611531552
Room No. 35A, Unit of [email protected]
Bhagwan Mahaveer m
Memorial Jain Trust,
Millers’ Road,
Vasanthnagar,
Benguluru-560052,
Karnataka, India.
Bangalore
KARNATAKA
Dr Jugesh Chattwal Christian Medical Department of 9316919718
College & Hospital Pediatrics Ground floor 01612220002
Ludhiana - 141008, [email protected]
Punjab, India.
Ludhiana
PUNJAB
Dr Mohini Apte Government Medical Dept of 07122744671
College & Hospital Paediatrics,Medical 07122701637
College Square, [email protected]
Nagpur- 440003, n
Maharashtra, India
Nagpur
MAHARASHTRA
Dr Reetesh Gupta Indraprastha Apollo Department of 9818214486
Hospitals Paediatric Cardiology,
1st floor Sarita Vihar, [email protected]
Delhi- Mathura Roads, m
Delhi-110076, India
Dept:
South
DELHI
Dr Monjori Mitra Institute of Child Health Department of 9831075734
Pediatrics, Room No. 03322893242
113, Ground floor, 11, [email protected]
Dr. Biresh Guha Street,
Kolkata 700017, West
Bengal, India.
Kolkata
WEST BENGAL
Dr Sanjay Desai M S Ramaiah Medical Department Of 9845290575
College & Hospitals Vascular And 08023601982
Endovascular Surgery, [email protected]
Room No. 08,Ground
Floor, MSRIT Post,
Bangalore-560054,

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Karnataka, India
Bangalore
KARNATAKA
Dr Vikas Kohli Maharaja Agrasen Department of 9958728855
Hospital, Paediatric Cardiology, 911140777666
Punjabi Bagh, New drvkohliresearch@gmai
Delhi, 110026, India l.com
New Delhi
DELHI
Dr Venkatesh Reddy Manipal Hospitals #98, HAL Airport Road, 919880311511
Bengaluru - 560017, 08025207181
Karnataka, India Dept: [email protected]
Paediatric Cardiology
Bangalore
KARNATAKA
Dr Sidharth Sethi Medanta-The Medicity Department of 9868306235
Pediatrics, Sector 38,
Gurgaon, Haryana [email protected]
122001, India
Gurgaon
HARYANA
Dr Jashvant Patel Nirmal Hospital Pvt Ltd Dept: Adult OPD Room 919825129555
no. 109 1st floor Ring 912612313636
Road, Surat - 395002, drjashvant.patel@gmail
Gujarat India Dept: .com
Paediatric Cardiology
Surat
GUJARAT
Dr Varinder Bedi Sir Ganga Ram Dept of Vascular and 919910104842
Hospital Endovascular surgery 01166173891
Room no.:F-63 Floor: [email protected]
1st floor(Emergency m
Bldng) Sir Ganga Ram
Hospital Marg, Rajinder
Nagar, New Delhi
110060, India
New Delhi
DELHI
Details of Ethics Name of Committee Approval Status Date of Approval Is Independent Ethics
Committee Committee?
Bhagwan Mahaveer Submittted/Under No Date Specified No
Jain Hospital Ethics Review
Committee on Human
Research Bhagwan
Mahaveer Jain Hospital
A Unit of Bhagwan
Mahaveer Memorial
Jain Trust Millers’
Road, Multispecialty
Facilities Vasanthnagar,
Benguluru -560052,
Karnataka, India.
Ethic Committee of Submittted/Under No Date Specified No
Manipal Hospitals, Review
Manipal Hospital, # 98,
HAL Airport Road,
Bangalore.
Ethics Committee M. S. Approved 24/01/2017 No

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Ramaiah Medical
College and Hospitals,
MSR Nagar, MSRIT
Post, Bangalore-56005
Karnataka, India
Ethics Committee, Sir Approved 24/08/2017 No
Ganga Ram Hospital,
Sir Ganga Ram
Hospital, Marg,
Rajinder Nagar, New
Delhi - 110060, India
HM Patel Centre for Approved 04/09/2017 No
Medical Care and
Education Karamsad
Institutional Ethics Submittted/Under No Date Specified No
committee (IEC) Review
Department of
Pharmacology,
Government Medical
College,
Nagpur-440003,
Maharashtra, India
Institutional Ethics Submittted/Under No Date Specified No
Committee Christian Review
Medical College &
Hospital Ludhiana –
141008, Punjab, India.
Institutional Ethics
Committee
Institutional Ethics Submittted/Under No Date Specified No
Committee, Institute of Review
Child Health, 11. Dr.
Biresh Guha Street,
Kolkata 700017, West
Bengal, India.
Institutional Ethics Submittted/Under No Date Specified No
Committee, Maharaja Review
Agrasen Hospital, R.
No. 614, 6th Floor,
West Punjabi Bagh,
New Delhi, 110026,
India
Institutional Ethics Submittted/Under No Date Specified No
Committee- Clinical Review
Studies, Indraprastha
Apollo Hospitals, New
Delhi, Mathura Roads,
Sarita Vihar, Delhi-
2110076, India
Medanta Institutional Submittted/Under No Date Specified No
Ethics Committee Review
POCU Unit, 10th Floor
(MDRI), Medanta-The
Medicity, Sector 38,
Gurgaon, Haryana
122001, India
Nirmal Hospital Private Approved 14/02/2017 No
limited Ethics
Committee, Nirmal

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Hospital Pvt ltd, Ring

Road, Surat 395002,
Gujarat, India
Regulatory Clearance Status Date
Status from DCGI
Approved/Obtained 29/12/2017
Health Condition / Health Type Condition
Problems Studied
Patients Acute embolism and thrombosis of deep veins of
lower extremity
Intervention / Type Name Details
Comparator Agent
Comparator Agent Comparator Standard of Care SoC treatment will be dispensed
(SoC)Treatment Arm to the subject on a monthly visit
schedule. Subjects will receive
SOC anticoagulant according to
the site’s SOC treatment, as
follows (alone or combination): -
LMWH (alone or followed with
VKA) - SP Xa inhibitors (alone
or followed with VKA) - Vitamin
K antagonist (VKA)In case of
centrally sourced SOC
treatment, the Sponsor will only
provide enoxaparin as LMWH,
fondaparinux as SP Xa inhibitor,
or warfarin as VKA with limited
presentations. The subject will
be treated with enoxaparin or
fondaparinux or
warfarin/heparin, with the
following suggestion: -
Enoxaparin – Subjects will be
treated with enoxaparin alone or
can be switched to warfarin
anytime during the study
treatment period. - Enoxaparin
will be provided as solution for
subcutaneous (SC) injection in
pre-filled syringes with only 40
mg/0.4 mL, 60 mg/0.6 mL, 80
mg/0.8 mL concentration or in
multiple dose vials (300 mg/3.0
mL) for injection. -
Fondaparinux – Subjects will be
treated with fondaparinux alone
or can be switched to warfarin
anytime during the study
treatment period. -
Fondaparinux will be supplied
as solution for SC injection in
pre-filled syringes (2.5mg/0.5
mL, 5.0 mg/0.4 mL, 7.5 mg/0.6
mL, and 10.0 mg/0.8 mL). -
Warfarin will be supplied as
tablets (0.5 mg, 1 mg, 2.5 mg).
Intervention Intervention Edoxaban (12 to 18 years old) will receive
Treatment arm tablets (15 and/or 30 mg
strength. Orally once a day for 3
months (with option for
extended treatment for

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additional 9 months ). Subjects

younger than 12 years of age
will receive edoxaban granules
for oral suspension. In each
cohort, doses will be selected to
elicit target exposures
comparable to those achieved
from adult doses of 60 mg if no
dose adjustment needed.
Dosing regimen will be
determined from Phase 1 single
dose study U157 and population
based PK.
Inclusion Criteria Inclusion Criteria
Age From 0.00 Month(s)
Age To 17.00 Year(s)
Gender Both
Details Subjects must satisfy all of the following criteria to be<br/> included
in the study:<br/> 1. Male or female pediatric subjects between birth
(defined as 38 weeks gestational age) and less than 18 years of age
at the time of consent.<br/> 2. Pediatric subjects with the presence
of documented VTE confirmed by appropriate diagnostic imaging
and requiring anticoagulant therapy for at least 90 days.<br/> 3.
Subjects must have received at least 5 days of heparin (LMWH or
SP Xa inhibitors or UFH according to the edoxaban label for VTE
treatment)<br/> therapy prior to randomization to treat the newly
identified index VTE. In addition, prior to being randomized to
edoxaban or SOC, subjects initially treated with VKA are
recommended to have an INR < 2.0.<br/> 4. Subject and/or
parent(s)/legal guardian(s) or legally acceptable representative is
informed and provides signed consent for the child to participate in
the study with edoxaban treatment. Pediatric subjects with
appropriate intellectual maturity will berequired to sign an assent
form in addition to the signed informed consent from the
parent(s)/legal guardian(s) or any legally acceptable
representative.<br/> 5. Female subjects who have menarche must
test negative for pregnancy at Screening and must consent to avoid
becoming pregnant by using an approved contraception method
throughout the study<br/>
Exclusion Criteria Exclusion Criteria
Details 1. Subjects with active bleeding or high risk of bleeding
contraindicating treatment with LMWH, SP Xa inhibitors, VKAs, or
direct oral anticoagulants (DOACs; identified high risk of bleeding
during prior experimental administration of DOACs).
2. Subjects who have been or are being treated with thrombolytic
agents, thrombectomy or insertion of a caval filter for the newly
identified index VTE.
3. Administration of antiplatelet therapy is contraindicated in both
arms except for low dose aspirin defined as 1-5 mg/Kg/day with
maximum of 100 mg/day.
4. Subjects with hepatic disease associated with coagulopathy
leading to a clinically relevant bleeding risk (aPTT > 50 seconds or
international normalized ratio [INR] > 2.0 not related to
anticoagulation therapy) or ALT > 5 × the upper limit of normal (ULN)
or total bilirubin > 2 × ULN with direct bilirubin > 20% of the total at
Screening Visit.
5. Subjects with glomerular filtration rate (GFR) 6. Subjects with
stage 2 hypertension defined as blood pressure (BP) systolic and/or
diastolic confirmed > 99th percentile + 5 mmHg

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7. Subject with thrombocytopenia 8. Life expectancy less than the

expected study treatment duration (3 months).
9. Subjects who are known to be pregnant or breastfeeding.
10. Subjects with any condition that, as judged by the Investigator,
would place the subject at increased risk of harm if he/she
participated in the study.

Method of Generating Computer generated randomization

Random Sequence
Method of Centralized
Concealment
Blinding/Masking Open Label
Primary Outcome Outcome Timepoints
The primary objective is to demonstrate the 3 months
non-inferiority
of edoxaban to standard of care (SOC; including
low
molecular weight heparin (LMWH), vitamin K
antagonist
(VKA), or synthetic pentasaccharide (SP) Xa
inhibitors) in
the treatment and secondary prevention of VTE
in pediatric subjects with regard to the composite
efficacy endpoint (ie,
symptomatic recurrent VTE, death as result of
VTE, and no change or extension of thrombotic
burden) during the first 3-month treatment
period.

Secondary Outcome Outcome Timepoints

- To compare edoxaban against SOC with During treatment or within 3 days of completing
regard to the combination of major and clinically or interrupting or stopping study treatment during
relevant non-major (CRNM) bleedings occurring the first 3-month treatment period.
during treatment or within 3 days of completing
or interrupting or stopping study treatment during
the first 3-month treatment period.
- To compare edoxaban against SOC with first to last dose plus 30 days
regard to a combination of major and CRNM
bleedings and symptomatic recurrent VTE, and
death as result of VTE which occur from first to
the last dose plus 30 days.

- To compare edoxaban against SOC with first to the last dose plus 30 days
regard to all bleedings which occur from first to
the last dose plus 30 days
- To compare edoxaban against SOC with first to the last dose plus 30 days
regard to the composite efficacyendpoint as
described in the primary objective from
randomization to the lastdose plus 30 days.
- To compare edoxaban against SOC with randomization to the last dose plus 30 days.
regard to all-cause mortality from randomization
to the last dose plus 30 days.
- To compare edoxaban against SOC with 3 months
regard to individual components of the
composite efficacy endpoints as described in the
primary objective during the first 3-month

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treatment period.
- To compare edoxaban against SOC with 3 months
regard to occurrence of DVT, catheter-related
thrombosis, sinovenous thrombosis within and
after thefirst 3-month treatment period
- To compare edoxaban against SOC with first to the last dose plus 30 days.
regard to composite combination of major and
CRNM bleedings from first to the last dose plus
30 days.
- To characterize the multiple dose Day 5
pharmacokinetics of edoxaban in pediatric
subjects at Day 5 using population
pharmacokinetic (PK) analysis (apparent
systemic clearance [CL/F] and apparent volume
of distribution [V/F]) and to assess the effect of
covariates such as age, body weight, and renal
function on the PK of edoxaban.
- To evaluate the relationship between edoxaban During the entire study
exposure and safety (such as bleeding) and
efficacy (thromboembolic events).

- To characterize the effect of edoxaban on During the entire study

biomarkers of coagulation (ie, prothrombin time
[PT], activated partial thromboplastin time
[aPTT], and anti-activated factor X [anti-FXa]).
Target Sample Size Total Sample Size=274
Sample Size from India=45
Final Enrollment numbers achieved (Total)=Applicable only for Completed/Terminated trials
Final Enrollment numbers achieved (India)=Applicable only for Completed/Terminated trials
Phase of Trial Phase 3
Date of First 30/01/2018
Enrollment (India)
Date of First 27/01/2017
Enrollment (Global)
Estimated Duration of Years=4
Trial Months=6
Days=0
Recruitment Status of Open to Recruitment
Trial (Global)
Recruitment Status of Open to Recruitment
Trial (India)
Publication Details Not yet available
Brief Summary This study is designed to test the hypothesis that the administration of edoxaban
after at least 5 days of heparin (LMWH or SP Xa inhibitors or UFH; with
overlapping VKAs if needed) is non-inferior to SOC (SOC; including LMWH, SP
Xa inhibitors and/or VKA) in treating and preventing the composite of
symptomatic recurrent VTE, death as result of VTE, and no change or
progression in thrombotic burden after 3 months of therapy.

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