| CTRI Number |
CTRI/2018/06/014512 [Registered on: 12/06/2018] Trial Registered Prospectively |
| Last Modified On: |
12/02/2019 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
STEP 2 : Research study investigating how well semaglutide works in people with type 2 diabetes suffering from overweight or obesity. |
|
Scientific Title of Study
|
Effect and safety of semaglutide 2.4 mg once weekly in subjects with overweight or obesity and type 2 diabetes. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NN9536-4374, version -2.0, dated 21 Dec 2017 |
Protocol Number |
| U1111-1200-8148 |
UTN |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Designation |
|
| Affiliation |
|
| Address |
|
| Phone |
|
| Fax |
|
| Email |
|
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Anil N Shinde |
| Designation |
Director - CMRQ |
| Affiliation |
Novo Nordisk India Private Ltd. |
| Address |
Novo Nordisk India Private Ltd.
Plot No.32, 47 - 50,
EPIP Area, Whitefield,
Bangalore - 560 066
Bangalore
KARNATAKA
560066
India |
| Phone |
919148526835 |
| Fax |
918041123517 |
| Email |
ansd@novonordisk.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Anil N Shinde |
| Designation |
Director - CMRQ |
| Affiliation |
Novo Nordisk India Private Ltd. |
| Address |
Novo Nordisk India Private Ltd.
Plot No.32, 47 - 50,
EPIP Area, Whitefield,
Bangalore - 560 066
Bangalore
KARNATAKA
560066
India |
| Phone |
919148526835 |
| Fax |
918041123517 |
| Email |
ansd@novonordisk.com |
|
|
Source of Monetary or Material Support
|
| Novo Nordisk India Private Ltd. Plot No.32, 47 - 50, EPIP Area, Whitefield Bangalore Karnataka-560 066. |
|
|
Primary Sponsor
|
| Name |
Novo Nordisk AS |
| Address |
Novo Allé, 2880 Bagsvaerd
Denmark. |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Novo Nordisk India Private Ltd |
Plot No.32, 47 - 50, EPIP Area, Whitefield Bangalore Karnataka-560 066 |
|
Countries of Recruitment
Modification(s)
|
Argentina
Canada
Germany
Greece
India
Japan
Russian Federation
South Africa
Spain
United Arab Emirates
United Kingdom
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 20 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Debasis Basu |
Apollo Gleneagles Hospital |
Department of Endocrinology, Apollo Gleneagles Hospital, 58, Canal Circular Road, Kolkata, West Bengal-700054.
Kolkata
WEST BENGAL |
9831256908
drdebasis_b@apollohospitals.onmicrosoft.com |
| Dr Rajesh Khadgawat |
All India Institute of Medical Sciences |
Dept of Endocrinology & Metabolism, All India Institute of Medical Sciences. Ansari Nagar, New Delhi - 110029.
New Delhi
DELHI |
9891418190
rajeshkhadgawat@hotmail.com |
| Dr Harish Kumar |
Amrita Institute of Medical Sciences & Research Centre |
Dept. of Endocrinology & Diabetes, Amrita Institute of Medical Sciences & Research Centre, AIMS – Ponekkara, Kochi, Kerela-682041.
Ernakulam
KERALA |
9895545190
harishkumar@aims.amrita.edu |
| Dr Tirthankar Chaudhury |
Apollo Gleneagles Hospital |
Department of Endocrinology, Apollo Gleneagles Hospital, 58, Canal Circular Road, Kolkata, West Bengal-700054.
Kolkata
WEST BENGAL |
9831322394
tchaudhury67@yahoo.co.uk |
| Dr Banshi Saboo |
Dr Jivraj Mehta Samark Health Foundation Bakeri Medical Research Centre |
Department of Endocrinology, Dr Jivraj Mehta Samark Health Foundation Bakeri Medical Research Centre, Near Shreyas Crossing Road, Dr Jivraj Mehta Marg, Jivraj park Paldi, Ahmedabad, Gujarat -380007.
Ahmadabad
GUJARAT |
9824047676
banshisaboo@hotmail.com |
| Dr Sailesh Lodha |
Eternal Hospital |
A unit of Eternal Heart Care Centre & Research Institute Pvt. Ltd" 3 A, Jagatpura Road, Near Jawahar Circle Jaipur,Rajasthan-302017
Jaipur
RAJASTHAN |
9829019055
saileshlodha@gmail.com |
| Dr Ajay Aggarwal |
Fortis Hospital |
A Block, Shalimar Bagh New Delhi New Delhi 110088
New Delhi
DELHI |
9818691391
endocrinologist39@yahoo.co.in |
| Dr Hemant Gupta |
Grant Government Medical College & Sir JJ Hospital |
Department of Medicine, Grant Government Medical College & Sir JJ Hospital,,Main Building, Byculla, Mumbai, Maharashtra- 400008.
Mumbai
MAHARASHTRA |
9820095763
drhemantgupta@hotmail.com |
| Dr Ghanshyam Goyal |
ILS Hospital |
Saltlake, DD 6, Sector 1, Saltlake city Kolkata West Bengal 700064
Kolkata
WEST BENGAL |
9830400450
drgsgoyal@hotmail.com |
| Dr Tushar Bandgar |
KEM Hospital |
Department of Endocrinology, KEM Hospital, Parel, Mumbai, Maharashtra-400012.
Mumbai
MAHARASHTRA |
9820036275
drtusharb@gmail.com |
| Dr Jayanthy Ramesh |
King George Hospital |
Department of Endocrinology,Super Speciality Block, King George Hospital, Maharani Peta, Visakhapatnam,Andhra Pradesh -530002.
Visakhapatnam
ANDHRA PRADESH |
9848145445
drjayanthyramesh@gmail.com |
| Dr R Balamurgan |
Kovai Diabetes Speciality Center And Hospital |
Department of endocrinology, Kovai Diabetes Speciality Center and Hospital, Shop No.15, Ram Nagar, Landmark: Near Vivekananda Rd, Ramnagar, Coimbatore, Tamil Nadu-641009.
Coimbatore
TAMIL NADU |
9842244881
rbmkdsc@gmail.com |
| Dr Prasun Deb |
Krishna Institute of Medical Sciences |
1-8-31/1, Minister Road, Secunderabad Telangana 500003
Hyderabad
ANDHRA PRADESH |
9849054877
prasundeb2002@yahoo.co.uk |
| Dr Suryanarayana Keshava Murthy |
M S Ramaiah Medical College and Hospitals |
MS Ramaiah Nagar,MSRIT Post, Bangalore Karnataka 560054
Bangalore
KARNATAKA |
9742971563
dr.suryanarayana@gmail.com |
| Dr Vijay Viswanathan |
M.V. Hospital for Diabetes Pvt Ltd |
No.4, West Mada Church Street, Royapuram Chennai Tamil Nadu 600 013
Chennai
TAMIL NADU |
04425954913
drvijay@mvdiabetes.com |
| Dr Vishwanathan Mohan |
Madras Diabetes Research Foundation |
Department of Diabetology, Madras Diabetes Research Foundation, #4, Conran Smith Road, Gopalapuram, Chennai, Tamil Nadu-600086.
Chennai
TAMIL NADU |
044-43968888
drmohans@diabetes.ind.in |
| Dr Reema Kashiva |
Noble Hospital Pvt. Ltd |
Department of Diabetes and Obesity, Noble Hospital Pvt. Ltd, 153 Magarpatta City Road, Hadaspar, Pune, Maharashtra-411013
Pune
MAHARASHTRA |
9922618286
reemakashiva@gmail.com |
| Dr Shehla Shaikh |
Prince Aly Khan Hospital |
Dept of Endocrinology, Prince Aly Khan Hospital, Aga Hall Nesbit Road, Mazagaon, Mumbai, Maharashtra-400010
Mumbai
MAHARASHTRA |
9820984842
drshehla@rediffmail.com |
| Dr Nikhil M Bhagwat |
Topiwala National Medical College and B.Y.L. Nair Charitable Hospital |
Department of Endocrinolgy, Topiwala National Medical College and B.Y.L. Nair Charitable Hospital, Dr A.L. Nair Road,Mumbai,Maharashtra- 400008.
Mumbai
MAHARASHTRA |
9820238399
bhagwatnik@yahoo.co.in |
| Dr V N Shah |
Zydus Hospitals and healthcare research pvt.Ltd |
Zydus hospital road,Near Sola Bridge,Thaltej Ahmedabad Gujarat 380054
Ahmadabad
GUJARAT |
9825067065
vnshah@zydushospitals.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 18 |
| Name of Committee |
Approval Status |
| DR. JIVRAJ MEHTA SMARAK HEALTH FOUNDATION |
Approved |
| Eternal Heart Care Centre and Research Institute |
Approved |
| Ethics committee ils hospital |
Approved |
| Ethics committee M S Ramaiah |
Approved |
| Ethics Committee, Prof. M Vishwanthan Diabetes Research Centre |
Approved |
| Institute Ethics Committee Madras Diabetes Research Foundation |
Approved |
| Institutional Ethics Committee AIIMs |
Approved |
| Institutional Ethics Committee Amrita institute |
Approved |
| Institutional Ethics Committee Apollo Gleneagles |
Approved |
| Institutional Ethics Committee Apollo Gleneagles |
Approved |
| Institutional Ethics Committee BYL Nair Hospital |
Approved |
| Institutional Ethics Committee Fortis Hospital |
Approved |
| Institutional Ethics Committee Grant Govt medical college |
Approved |
| Institutional Ethics Committee KEM Hospital |
Approved |
| Institutional Ethics Committee Kovai Diabetes Specialty Center |
Approved |
| Institutional Ethics Committee Noble Hospital |
Approved |
| Institutional Ethics Committee, Zydus Hospital |
Approved |
| KIMS Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: E11||Type 2 diabetes mellitus, Type 2 Diabetes, Overweight or obesity. , |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Comparator Agent |
Placebo |
2.4mg/1.0mg once weekly prefilled pen injector for sub cutaneous injection |
| Intervention |
Semaglutide |
2.4mg/1.0mg once weekly prefilled pen injector for sub cutaneous injection |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
2. Male or female, age ≥ 18 years at the time of signing informed consent.
3. Body Mass Index (BMI) ≥ 27 kg/m2
4. History of at least one self-reported unsuccessful dietary effort to lose body weight
5. Diagnosed with T2D ≥ 180 days prior to the day of screening
6. Subject treated with either:
i. diet and exercise alone or stable treatment with metformin, SU, SGLT2i, glitazone as single agent therapy or
ii. up to 3 OADs (metformin, SU, SGLT2i or glitazone) according to local label
7. HbA1c 7-10% (53-86 mmol/mol) (both inclusive) |
|
| ExclusionCriteria |
| Details |
Diabetes Related:1. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior day of screening
2. Receipt of any other anti-diabetic investigational drug within 90 days prior to screening for this trial, or receipt of any investigational drugs not affecting diabetes within 30 days prior to screening for this trial
3. Treatment with a GLP-1 receptor agonist within 180 days prior to screening
4. Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of < 30 mL/min/1.73 m2 (< 60 mL/min/1.73 m2 in subjects treated with SGLT2i ) according to CKD-EPI creatinine equation as defined by KDIGO 201242 by the central laboratory at screening
5. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or an equally qualified health care provider (e.g. optometrist) within the past 90 days prior to screening or in the period between screening and randomisation
Obesity related:
6. A self-reported change in body weight > 5 kg (11 lbs) within 90 days before screening irrespective of medical records
7. Previous or planned (during the trial period) obesity treatment with surgery or a weight loss device. However, the following are allowed: (1) liposuction and/or abdominoplasty, if performed > 1 year before screening, (2) lap banding, if the band has been removed > 1 year before screening, (3) intragastric balloon, if the balloon has been removed > 1 year before screening or (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed > 1 year before screening
8. Uncontrolled thyroid disease, defined as thyroid stimulating hormone (TSH) > 6.0 mIU/L or < 0.4 mIU/L as measured by central laboratory at screening
Mental Health:
9. History of major depressive disorder within 2 years before screening
10. Diagnosis of other severe psychiatric disorder (e.g., schizophrenia, bipolar disorder)
11. A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15 at screening
12. A lifetime history of a suicidal attempt
13. Suicidal behaviour within 30 days before screening
14. Suicidal ideation corresponding to type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) within the past 30 days before screening
General safety:
15. Use of non-herbal Chinese medicine or other non-herbal local medicine with unknown/unspecified content within 90 days before screening
16. Presence of acute pancreatitis within the past 180 days prior to the day of screening
17. History or presence of chronic pancreatitis
18. Calcitonin ≥ 100 ng/L as measured by the central laboratory at screening
19. Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
20. History of malignant neoplasms within the past 5 years prior to screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed
21. Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina or transient ischaemic attack within the past 60 days prior to screening
22. Subject presently classified as being in New York Heart Association (NYHA) Class IV
23. Surgery scheduled for the duration of the trial, except for minor surgical procedures, in the opinion of the investigator
24. Known or suspected abuse of alcohol or recreational drugs
25. Known or suspected hypersensitivity to trial product(s) or related products
26. Previous participation in this trial. Participation is defined as signed informed consent
27. Participation in another clinical trial within 90 days before screening
28. Other subject(s) from the same household participating in any semaglutide trial
29. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method
30. Any disorder, unwillingness or inability, not covered by any of the other exclusion criteria, which in the investigator’s opinion, might jeopardise the subject’s safety or compliance with the protocol. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Change in body weight from baseline |
68 Weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To compare effect of semaglutide s.c. 2.4 mg onceweekly versus semaglutide placebo I/II in achieving weight reduction of ≥ 10% and ≥ 15%. |
68 Weeks |
| To compare effect of semaglutide s.c. 2.4 mg once weekly versus semaglutide placebo I/II, on waist circumference |
68 weeks |
| To compare effect of semaglutide s.c. 2.4 mg once weekly versus semaglutide s.c. 1.0mg once-weekly, on body weight |
68 Weeks |
| To compare the effect of semaglutide s.c. 2.4 mg once weekly versus semaglutide placebo I/II on body weight, BMI,and fasting plasma glucose . |
68 Weeks |
| To compare the effect of semaglutide s.c. 1.0 mg once weekly versus semaglutide placebo I/II on HbA1c |
68 Weeks |
|
Target Sample Size
Modification(s)
|
Total Sample Size="1210"
Sample Size from India="164"
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 Enrollment (India)
Modification(s)
|
26/07/2018 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
04/06/2018 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
na |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
This is a 68-week, randomised, double-blinded, double dummy, placebo-controlled, multicentre trial. Subjects will be randomised in a 1:1:1 manner to receive either:
- Semaglutide s.c. 2.4 mg and semaglutide placebo II once-weekly
- Semaglutide s.c. 1.0 mg and semaglutide placebo I once-weekly
- Semaglutide placebo I and semaglutide placebo II once-weekly
All as an adjunct to a reduced-calorie diet and increased physical activity.
There is a 1 week screening period followed by a randomisation visit and a 68-week treatment period. The treatment period is divided into a dose escalation period of 16 weeks and a maintenance period of 52 weeks. Subsequently there is a follow-up period of 7 weeks. The trial population will consist of subjects with BMI > 27 kg/m2 with T2D on 0-3 OADs but not treated with insulin. |