| CTRI Number |
CTRI/2019/08/020642 [Registered on: 09/08/2019] Trial Registered Prospectively |
| Last Modified On: |
03/10/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
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Type of Study
|
Drug
Other (Specify) [Dapagliflozin and Saxagliptin] |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
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Public Title of Study
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A clinical trial conducted in pediatric patients with Type 2 Diabetes Mellitus who are of age between 10 to 18 years to evaluate the safety and efficacy of Dapagliflozin 5 and 10 mg and Saxagliptin 2.5 and 5 mg for 26 weeks with a 26 week Safety Extension Period |
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Scientific Title of Study
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A 26 Week, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Parallel Group, Phase 3 Trial with a 26 Week Safety Extension Period Evaluating the Safety and Efficacy of Dapagliflozin 5 and 10 mg, and Saxagliptin 2.5 and 5 mg in Pediatric Patients with Type 2 Diabetes Mellitus who are between 10 and below 18 years of age |
| Trial Acronym |
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Secondary IDs if Any
Modification(s)
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| Secondary ID |
Identifier |
| CV181375/D1680C00019-V 08(India only),dated 04-OCT-2022 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
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| Name |
Dr Aparna Parikh |
| Designation |
Executive Director & Country Consultant for India |
| Affiliation |
Pharmaceutical Research Associates India Pvt. Ltd |
| Address |
The Qube, A-603, C.T.S. No. 1498, A/2 M.V. Road, Marol, Andheri (East) Mumbai (Suburban)
Mumbai
The Qube, A-603, C.T.S.No.1498 A/2 M.V. Road, Marol, Andheri (East), Mumbai Mumbai (Suburban)
Mumbai (Suburban)
MAHARASHTRA
400059
India |
| Phone |
91-2271234107 |
| Fax |
91-2271234198 |
| Email |
ParikhAparna@prahs.com |
|
Details of Contact Person
Public Query
|
| Name |
Jigar Lakhani |
| Designation |
Clinical Team Manager |
| Affiliation |
Pharmaceutical Research Associates India Pvt. Ltd |
| Address |
The Qube, A-603, C.T.S. No. 1498, A/2 M.V. Road, Marol, Andheri (East) Mumbai (Suburban)
Mumbai
The Qube, A-603, C.T.S.No.1498 A/2 M.V. Road, Marol, Andheri (East), Mumbai Mumbai (Suburban)
Mumbai (Suburban)
MAHARASHTRA
400059
India |
| Phone |
91-2271234129 |
| Fax |
91-2271234198 |
| Email |
LakhaniJigar@prahs.com |
|
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Source of Monetary or Material Support
|
| AstraZeneca AB, 151 85 Södertälje, Sweden |
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Primary Sponsor
|
| Name |
AstraZeneca |
| Address |
AB, 151 85 Södertälje, Sweden |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
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| Name |
Address |
| Pharmaceutical Research Associates India Pvt Ltd |
The Qube, A-603, C.T.S. No. 1498, A/2 M.V. Road, Marol, Andheri (East) Mumbai 400059 Maharashtra India |
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Countries of Recruitment
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Argentina
Australia
Brazil
Chile
China
Colombia
Finland
India
Italy
Malaysia
Mexico
New Zealand
Philippines
Poland
Republic of Korea
Russian Federation
Thailand
Turkey
Ukraine
United Kingdom
United States of America
Canada
Romania
Taiwan |
Sites of Study
Modification(s)
|
| No of Sites = 12 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Subrata Dey |
Apollo Gleneagles Hospital - Kolkata |
Clinical Trial & Research Department, 58 Canal Circular Road,
Kolkata-700054
Kolkata
WEST BENGAL |
9836542460
sbrtdey@yahoo.com |
| Dr Raveendra Kodur |
Bangalore Medical College and Research Institute (BMCRI) - Vanivilas Hospital |
Room No 72/A,second Floor,Medicine New C Block, Victoria Hospital, Fort, Bangalore-
Bangalore
KARNATAKA |
9448134587
drkrraveendra@gmail.com |
| Dr Rajendra Agrawal |
Diabetes Care & Research Centre S.P.Medical College & AG of Hospitals |
Clinical Research Unit (room No. 113 & 114),P.B.M. HOSPITAL CAMPUS, S.P. MEDICAL COLLEGE, BIKANER-334 003,RAJASTHAN,INDIA
Bikaner
RAJASTHAN |
9414142931
drrpagrawal@yahoo.co.in |
| Dr Neeraj Manikath |
Government Medical College |
Department of General Medicine, Kozhikode-673008
Kozhikode
KERALA |
9030001031
drneerajresearch@gmail.com |
| Dr Subramanyam Kandregula |
King George Hospital |
Super Speciality Block, Department of Endocrinology, King George Hospital, Maharani Peta, Visakhapatnam-530001
Visakhapatnam
ANDHRA PRADESH |
9848149536
kavsendo@yahoo.co.in |
| Dr Balamurugan Ramanathan |
Kovai Diabetic Speciality Centre & Hospital |
5, Vivekananda Road, Ramnagar, Coimbatore-641009
Coimbatore
TAMIL NADU |
4224377732
rbmkdsc@gmail.com |
| Dr Deepak Bhosle |
Mahatma Gandhi Missions Medical College (MGM Hospital) |
Department of research,Â
N-6 CIDCO, Aurangabad-431003
Aurangabad
MAHARASHTRA |
7770087870
drdeepakbhosle@gmail.com |
| Dr Rakesh Sahay |
Osmania General Hospital-OGH |
Department of Endocrinolody,2nd Floor,Afzal Gunj, Hyderabad-500012
Visakhapatnam
ANDHRA PRADESH |
9849597570
sahayrk@gmail.com |
| Dr Mohan Magdum |
Poona Hospital and Research Centre |
Research Department,27, L B Shastri Road, Sadashiv Peth, Nr. Alka Theatre, Pune-411030
Pune
MAHARASHTRA |
9822217243
mohanmagdum@gmail.com |
| Dr Anil Bhansali |
Postgraduate Institute of Medical Education & Research (PGIMER) |
Nehru Hospital, 4th floor, F Block, Room No.8, Chandigarh-160012
Chandigarh
CHANDIGARH |
01722756583
anilbhansaliendocrine@gmail.com |
| Dr Prakash Kurmi |
Shivam Hospital |
C-4,Department of Endocrinology, Satyanarayan Society, Maninagar (East), Ahmedabad-380008
Ahmadabad
GUJARAT |
9825047692
dr_prakashkurmi@yahoo.co.in |
| Dr Pravin Supe |
Supe Heart & Diabetes Hospital and Research Centre |
Reseach Department,Opp. Adharashram, Gharpure Ghat, Near Rungta School, Ashok Stambh, Nashik-422002
Nashik
MAHARASHTRA |
9405666165
pravinsupe@ymail.com |
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Details of Ethics Committee
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| No of Ethics Committees= 12 |
| Name of Committee |
Approval Status |
| Ethics Committee of Bangalore Medical College and Research Institute |
Approved |
| Ethics Committee Osmania General College |
Approved |
| Ethics Committee S.P Medical College and A.G Hospitals |
Approved |
| Institutional Ethics Committee - Government Medical College |
Approved |
| Institutional Ethics Committee of Kovai Diabetic Speciality Centre & Hospital |
Approved |
| Institutional Ethics Committee- Apollo Gleneagles Hospital |
Approved |
| Institutional Ethics Committee- King George Hospital |
Approved |
| Institutional Ethics Committee-(PGIMER) |
Approved |
| MGM Ethics Committee for Research on Human Subjects |
Approved |
| Shivam Hospital Ethics Committee |
Approved |
| Supe Hospital Ethics Committee |
Approved |
| The Ethics Committee Poona Medical Hospital & Research |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: E119||Type 2 diabetes mellitus without complications, |
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Intervention / Comparator Agent
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| Type |
Name |
Details |
| Intervention |
Dapagliflozin |
Dapagliflozin is a rationally designed, stable, competitive, reversible, highly selective and orally active inhibitor of SGLT-2, the major transporter responsible for renal glucose reabsorption.
Dapagliflozin 5 mg and 10 mg
Frequency- once Daily
Duration - 52 weeks |
| Comparator Agent |
Placebo |
Placebo to Match Dapagliflozin 5 mg and 10 mg and Saxagliptin 2.5mg/5mg
Frequency- Once Daily
Duration- 52 Weeks |
| Intervention |
Saxagliptin |
Saxagliptin (BMS-477118) is a highly potent, selective, reversible, and competitive DPP-4 inhibitor. Dipeptidyl peptidase 4 is the enzyme responsible for the inactivation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. Saxagliptin 2.5mg/5mg
Frequency - Once Daily
Duration - 52 Weeks |
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Inclusion Criteria
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| Age From |
10.00 Year(s) |
| Age To |
18.00 Year(s) |
| Gender |
Both |
| Details |
a)Previously diagnosed with T2DM by World Health Organization/ADA criteria
b)HbA1c greater than or equal to 6.5% and less than or equal to 10.5% obtained at screening visit
c)Currently on diet and exercise and stable dose of at least 1000 mg metformin (IR or XR) for a minimum of 8 weeks, or stable dose of insulin for a minimum of 8 weeks, or a stable combination of at least 1000 mg metformin (IR or XR) and insulin for a minimum of 8 weeks prior to randomization
d)Male and female patients eligible if 10 years of age, up to but not including 18 years of age at the time of enrollment/screening. At least 30% of total subjects will be between the ages of 10 and 14 years and at least one third but no more than two thirds, female subjects. |
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| ExclusionCriteria |
| Details |
a)Presence of Type 1 diabetes, as demonstrated by:
1. Preexisting diagnosis of Type 1 diabetes,OR
2.Positivity at screening of either antibodies to glutamic acid decarboxylase (GAD) or protein tyrosine phosphatase-like protein antibodies (IA-2) AND abnormally low levels of C-peptide. GAD and IA-2 antibody testing will be performed in all screened subjects, C-peptide only in otherwise eligible, antibody-positive subjects. All instances of antibody-positive subjects with normal or elevated C-peptide values will be discussed by the Investigator with the study med ical monitors and Sponsor’s study director to confirm study eligibility.
b)Previous diagnosis of monogenic etiology of Type 2 diabetes such as maturity onset diabetes of the young (MODY), genetic disorders with strong associations with insulin resistance/diabetes and/or obesity such as Turner’s Syndrome and Prader-Willi, or secondary diabetes (steroid use, Cushing’s disease, acromegaly), secondary diabetes mellitus, or diabetes insipidus.
c)Diabetes ketoacidosis (DKA) within 6 months of screening
d)Current use of the following medications for the treatment of diabetes, or use within the specified timeframe prior to screening for the main study:
i.Eight weeks: sulfonylureas, alpha glucosidase inhibitors, metiglinide, oral or injectable incretins or incretin mimetics, other antidiabetes medications not otherwise specified
ii.Sixteen weeks: thiazolidinediones. DPP-4 inhibitors (with no reported medication related AEs related to DPP-4 inhibitors), sodium glucose cotransporter-2 (SGLT-2) inhibitors (with no reported medication related AEs related to SGLT-2 inhibitors) |
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Method of Generating Random Sequence
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Stratified randomization |
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Method of Concealment
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Centralized |
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Blinding/Masking
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Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded |
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Primary Outcome
|
| Outcome |
TimePoints |
| Change in HbA1C from baseline to week 26 after 26 weeks of double blind, add-on oral therapy of Dapagliflozin or Saxagliptin compared to placebo |
Change in HbA1c from baseline to week 26 |
|
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Secondary Outcome
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| Outcome |
TimePoints |
| Change in Fasting Plasma Glucose (FPG) from baseline to Week 26 |
Week 26 |
| Percentage of subjects with baseline HbA1c ≥ 7% who achieve an HbA1c level of less than 7.0% |
Week 26 |
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Target Sample Size
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Total Sample Size="243"
Sample Size from India="37"
Final Enrollment numbers achieved (Total)= "256"
Final Enrollment numbers achieved (India)="10" |
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Phase of Trial
|
Phase 3 |
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Date of First Enrollment (India)
|
09/08/2019 |
| Date of Study Completion (India) |
25/10/2023 |
| Date of First Enrollment (Global) |
05/07/2017 |
| Date of Study Completion (Global) |
02/01/2024 |
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Estimated Duration of Trial
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Years="4"
Months="6"
Days="10" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
|
Available |
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
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The proposed study is a 26-week Phase 3b, multicenter, randomized, placebo-controlled, double-blind, parallel-group study with a 26-week safety extension period to evaluate the safety and efficacy of dapagliflozin (5 mg and 10 mg), and, separately, saxagliptin (2.5 mg and 5 mg) in pediatric subjects with T2DM with an additional post-study visit at Week 104 for assessment of measures of growth and maturity. Approximately 243 pediatric subjects globally and out of which 37 subjects from India will be randomized in a 1:1:1 ratio to receive dapagliflozin 5 mg, saxagliptin 2.5 mg, or placebo. Approximately 81 subjects will be randomized to each treatment arm.
After a 26-week, double-blind, short term treatment period, the primary efficacy endpoint (change in HbA1C from baseline to week 26 of treatment) will be assessed. This will be followed by a 26-week, site- and subject-blind long term safety extension period. Dapagliflozin and, separately, saxagliptin will be compared against the single shared placebo comparator.
Measures of growth and maturity will be assessed at the Week 104 post-study visit. |