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CTRI Number  CTRI/2022/07/043808 [Registered on: 07/07/2022] Trial Registered Prospectively
Last Modified On: 12/12/2024
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 research study to see how well the new weekly medicine IcoSema, which is a combination of insulin icodec and semaglutide, controls blood sugar level in people with type 2 diabetes compared to weekly insulin icodec 
Scientific Title of Study   A 52-week study comparing the efficacy and safety of once weekly IcoSema and once weekly insulin icodec, both treatment arms with or without oral anti-diabetic drugs, in participants with type 2 diabetes inadequately controlled with daily basal insulin. COMBINE 1 
Trial Acronym  COMBINE 1 
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
2020-005281-34  EudraCT 
NN1535-4591, Version 3.0 dated 10 Aug 2021  Protocol Number 
NN1535-4591,Version 6.0, dated 23 Mar 2023  Protocol Number 
U1111-1260-8259  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
Modification(s)  
Name  Maya Sharma 
Designation  Vice President - CMR  
Affiliation  Novo Nordisk India Private Ltd. 
Address  Novo Nordisk India Private Limited, Nxt Tower - 2, Floor 1 & 2 Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli, Bangalore - 560045. India

Bangalore
KARNATAKA
560045
India 
Phone  09911497869  
Fax  080-41123518  
Email  yrms@novonordisk.com  
 
Details of Contact Person
Public Query
Modification(s)  
Name  Maya Sharma 
Designation  Vice President - CMR 
Affiliation  Novo Nordisk India Private Ltd. 
Address  Novo Nordisk India Private Limited, Nxt Tower - 2, Floor 1 & 2 Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli, Bangalore - 560045. India

Bangalore
KARNATAKA
560045
India 
Phone  09911497869  
Fax  080-41123518  
Email  yrms@novonordisk.com  
 
Source of Monetary or Material Support
Modification(s)  
Novo Nordisk AS Novo Alle, 2880 Bagsvaerd Denmark 
 
Primary Sponsor
Modification(s)  
Name  Novo Nordisk India Private Limited 
Address  Novo Nordisk India Private Limited Nxt Tower 2 Floor 1 & 2 Embassy Manyata Business Park Nagavara Village Kasaba Hobli Bangalore 560045 India 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Australia
Belgium
Bulgaria
China
Croatia
Finland
India
Italy
Japan
Mexico
Norway
Poland
Portugal
Republic of Korea
Romania
Russian Federation
Serbia
South Africa
Taiwan
Turkey
United States of America  
Sites of Study
Modification(s)  
No of Sites = 12  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Manash Baruah  Apollo Excelcare Hospital  Room no- 120, 1st floor OPD Block,Endocrinology & Diabetology Department, Apollo Excelcare Hospitals Near Ganesh Mandir, Paschim Boragaon, NH-37
Kamrup
ASSAM 		 9435018344

manashb2@gmail.com 
Dr Ameya Joshi  Bhakti Vedanta Hospital and Research Institute  Bhaktivedanta Swami Marg, Sector 6, Srishti Complex Mira Road, Mira Bhayandar
Thane
MAHARASHTRA 		 2223027163

ameyaable@gmail.com 
Dr Sharvil Gadve  Diabetes Corner, Excel Endocrine Center  Diabetes Corner, Excel Endocrine Center, 1708, E Ward, 4Th Lane, Nice Clinic, Rajarampuri, Kolhapur, Maharashtra 416008, India
Kolhapur
MAHARASHTRA 		 9552365977

sharvilgadve@gmail.com 
Dr Parag Rajnikant Shah   Gujarat Endocrine Centre  Gujarat Endocrine Centre, Silver Brook, 2nd Floor, Opp. doctor house Ambawadi, Ambawadi, Ahmedabad, Gujarat 380006, India
Ahmadabad
GUJARAT 		 9824042688

paragendo@gmail.com 
Dr Paturi Vishnupriya Rao  Kumudini Devi Diabetes Research Centre  Kumudini Devi Diabetes Research Centre, Ramdevrao Hospital (a unit of Sivananda Rehabilitation Home), Kukatpally, Hyderabad - 500072, Telangana, India
Hyderabad
TELANGANA 		 9885051110

raopaturi@gmail.com 
Dr Anupam Prakash   Lady Hardinge Medical College  Department of Medicine, Lady Hardinge Medical College, Shaheed Bhagat Singh Marg Opposite Shivajii Stadium, New Delhi, Delhi - 110001 India
New Delhi
DELHI 		 8588885305

prakashanupam@hotmail.com 
Dr Vijay Viswanathan   M.V. Hospital for Diabetes Private Limited  M.V. Hospital for Diabetes Private limited, No.4, W Madha Church St, Panaimarathotti, Pudumanaikuppam, Royapuram, Chennai, Tamil Nadu 600013, India
Chennai
TAMIL NADU 		 9840055535

drvijay@mvdiabetes.com 
Dr Sumaiya Anjum  Mysore Medical College and Research Institute  Dept. of Medicine,K.R. Hospital Irwin Road 570001 Karnataka
Mysore
KARNATAKA 		 7760218464

sumi_anjum262@yahoo.com 
Dr K Neelaveni  Osmania General Hospital  Department of Endocrinology, Osmania General Hospital, Afzalgunj, Hyderabad, 500095, India
Hyderabad
TELANGANA 		 9848131182

neelaveni1@yahoo.co.in 
Dr Sanjay Kumar Bhadada  Post Graduate Institute of Medical Education & Research  Department of Endocrinology, Post Graduate Institute of Medical Education & Research, Madhya Marg, Sector 12, Chandigarh - 160012, India
Chandigarh
CHANDIGARH 		 9876602448

bhadadask@rediffmail.com 
Dr Anurag Ranjan Lila   Seth G.S. Medical Collecge and K.E.M. Hospital  Department of Endocrinology, Seth G.S. Medical College and K.E.M. Hospital, Parel, Mumbai - 400012, Maharashtra, India
Mumbai
MAHARASHTRA 		 9323065346

anuraglila@gmail.com 
Dr Sunil M Jain  TOTALL Diabetes Hormone Institute  3rd Floor, TOTALL Diabetes Hormone Institute BCM Health Island, PU4, Scheme 54, Behind Prestige Management Institute Near Bombay Hospital
Indore
MADHYA PRADESH 		 7312433216

sunilmjain@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 12  
Name of Committee  Approval Status 
Bhakti Vedanta Hospital Ethics Committee  Approved 
Ethics Committee of Diabetes Thyroid Hormone Research Institute   Approved 
Excel Endocrine Centre Institutional EC  Approved 
Institutional Ethics Committee Osmania Medical College  Approved 
Institutional Ethics Committee Prof.M.Viswanathan Diabetes Research Centre  Approved 
Institutional Ethics Committee Ramdevrao Hospital (A unit of Sivananda Rehabilitation)  Approved 
Institutional Ethics Committee, Apollo-Excelcare Hospitals  Approved 
Institutional Ethics Committee, Mysore Medical College and Research Institution  Approved 
Institutional Ethics Committee-I, Seth GS Medical College and KEM Hospital  Approved 
LHMC, New Delhi, Delhi- 110001 India  Approved 
PGIMER, Chandigarh  Approved 
Sangini Hospital Ethics Committee Sangini Hospital  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: E11||Type 2 diabetes mellitus,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  IcoSema  IcoSema s.c. (into the thigh, upper arm or abdomen) 700 units/mL + 2 mg/mL. Administer IcoSema once weekly, on the same day each week, at any time of the day. Duration :52 Weeks  
Comparator Agent  Insulin icodec  Insulin icodec s.c. (into the thigh, upper arm or abdomen) 700 units/mL. Administer insulin icodec once weekly, on the same day each week, at any time of the day. Duration :52 Weeks 
 
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 study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
2. Male or female.
3. Age above or equal to 18 years at the time of signing informed consent.
4. Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days before screening.
5. HbA1c of 7.0-10.0% (53.0-85.8 mmol per mol) (both inclusive) as assessed by central laboratory on the day of screening.
6. Treated with once daily or twice-daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units per mL, or insulin glargine 300 units per mL) 20-80 units per day greater than or equal to 90 days before screening. Short term bolus insulin treatment for a maximum of 14 days before screening is allowed, as is prior insulin treatment for gestational diabetes. The treatment can be with or without any of the following anti-diabetic drugs with stable dose greater than or equal to 90 days before screening: Metformin, Sulfonylureasa, Meglitinides (glinides)a, DPP-4 inhibitorsa, Sodium-glucose co-transporter 2 inhibitors, Alpha-glucosidase-inhibitors, Thiazolidinediones, Marketed oral combination products only including the products listed above.
7. Body mass index (BMI)lesser than or equal to 40.0 kg per m2.
viii.Not currently using real time continuous or flash glucose monitoring. 
 
ExclusionCriteria 
Details  1. Known or suspected hypersensitivity to randomised treatment or related products.
2. Previous participation in this study. Participation is defined as signed informed consent.
3. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing
potential and not using a highly effective contraceptive method, as defined in Appendix 4.
4. Participation (i.e., signed informed consent) in any interventional, clinical study within 90 days
before screening.
Note: Simultaneous participation in a study with the primary objective of evaluating an
approved or non-approved investigational medicinal product for prevention or treatment of
COVID-19 disease or postinfectious conditions is allowed if the last dose of the investigational
medicinal product has been received more than 30 days before screening in the current study
and if simultaneous participation is allowed by local authorities.
5. Any disorder, except for conditions associated with T2D, which in the investigator’s opinion
might jeopardise participant’s safety or compliance with the protocol.
6. Anticipated initiation or change in concomitant medication (for more than 14 consecutive days)
known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or
systemic corticosteroids).
7. Treatment with any medication for the indication of diabetes or obesity other than stated in the
inclusion criteria within 90 days before screening.
8. Any episodesa of diabetic ketoacidosis within 90 days before screening.
9. Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary
thyroid carcinoma.
10. Presence or history of pancreatitis (acute or chronic) within 180 days before screening.
11. Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris
or transient ischaemic attack within 180 days before screening.
12. Chronic heart failure classified as being in New York Heart Association Class IV at screening.
13. Planned coronary, carotid or peripheral artery revascularisation.
14. Renal impairment measured as estimated glomerular filtration rate value of
< 30 ml/min/1.73 m2 at screening as defined by KDIGO 2012.20
15. Impaired liver function, defined as alanine aminotransferase ≥ 2.5 times or bilirubin > 1.5 times
upper normal limit at screening.
16. Known hypoglycaemic unawareness as indicated by the investigator according to Clarke’s
questionnaire question 8.21.
17. Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the
investigator.
18. Inadequately treated blood pressure defined as systolic ≥ 180 mmHg or diastolic ≥ 110 mmHg
at screening.
19. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus
examination performed within the past 90 days before screening or in the period between
screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a
digital fundus photography camera specified for non-dilated examination, see 8.2.4.
20. Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer,
in-situ carcinomas of the cervix, or in situ prostate cancer) within 5 years before screening.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Change in HbA1c  From baseline week 0 (V2) to week 52 (V54)
Unit - %-point 
 
Secondary Outcome  
Outcome  TimePoints 
Change in body weight  From baseline week 0 (V2) to week 52 (V54)
Unit - Kg 
Number of clinically significant
hypoglycaemic episodes (level 2) (3.0
mmol/L (54 mg/dL), confirmed by BG
meter) or severe hypoglycaemic episodes
(level 3) 		 From baseline week 0 (V2) to week 57 (V56)
Unit - Number of episodes 
 
Target Sample Size
Modification(s)  		 Total Sample Size="1290"
Sample Size from India="30" 
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)  		 07/10/2022 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  15/06/2022 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="1"
Days="10" 
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)?  

Response - NO
Brief Summary  
This is an interventional, multi-national, multi-centre, randomised, 52-week, open label, parallel group, treat-to-target, confirmatory study with two treatment arms.
 
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