| CTRI Number |
CTRI/2023/10/058480 [Registered on: 10/10/2023] Trial Registered Prospectively |
| Last Modified On: |
28/05/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
A Study of LY3502970 Versus Insulin Glargine in Adult Participants with Type 2 Diabetes and Obesity or Overweight |
|
Scientific Title of Study
|
A Phase 3, Open-Label Study of Once Daily LY3502970 Compared with Insulin Glargine in
Adult Participants with Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk (ACHIEVE-4) |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| J2A-MC-GZGS(c) protocol dated 21 Apr 2023 |
Protocol Number |
| NCT05803421 |
ClinicalTrials.gov |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Dr Manish Mistry |
| Designation |
Medical Director |
| Affiliation |
Eli Lilly and Company (India) Pvt. Ltd. |
| Address |
Plot No - 92, Sec - 32, Institutional Area, Gurgaon HARYANA-122001 India
Gurgaon
HARYANA
122001
India |
| Phone |
9820234897 |
| Fax |
|
| Email |
manish.mistry@lilly.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Manish Mistry |
| Designation |
Medical Director |
| Affiliation |
Eli Lilly and Company (India) Pvt. Ltd. |
| Address |
Plot No - 92, Sec - 32, Institutional Area, Gurgaon HARYANA-122001 India
Gurgaon
HARYANA
122001
India |
| Phone |
9820234897 |
| Fax |
|
| Email |
manish.mistry@lilly.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Rajeev Sharan Shrivastava |
| Designation |
Associate Director |
| Affiliation |
Eli Lilly and Company (India) Pvt. Ltd. |
| Address |
Plot No - 92, Sec - 32, Institutional Area, Gurgaon HARYANA-122001 India
Gurgaon
HARYANA
122001
India |
| Phone |
09810308697 |
| Fax |
|
| Email |
shrivastava_rajeev_sharan@lilly.com |
|
|
Source of Monetary or Material Support
|
|
Eli Lilly and Company (India) PVT LTD, Plot No. 92, Sector-32, Gurgaon, Haryana - 122001 |
|
|
Primary Sponsor
|
| Name |
Eli Lilly and Company India Pvt Ltd |
| Address |
Eli Lilly and Company (India) PVT LTD, Plot No. 92, Sector-32, Gurgaon, Haryana - 122001 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
Argentina
Austria
Brazil
Czech Republic
Germany
Greece
India
Italy
Mexico
Republic of Korea
Romania
Slovakia
Spain
Turkey
United States of America |
|
Sites of Study
|
| No of Sites = 12 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Neil Bardoloi |
Apollo Excelcare Hospital |
Pachim Boragaon Near Ganesh Mandir, NH 37
Guwahati Kamrup Metropolitan Assam - 781033 India
Kamrup
ASSAM |
9435703742
n.bardoloi.clinicalresearch@gmail.com |
| Dr Anil Jawaharani |
Central India Cardiology and Research Institute |
Plot no.1, Gawande Layout, Khamla, Nagpur, Maharashtra 440015
Nagpur
MAHARASHTRA |
9822220936
drjawahirani01@gmail.com |
| Dr Abhay Chandrashekar Khode |
Chellaram Diabetes Institute |
1st Floor, Lalani Quantum, Bavdhan (Budruk), Pune-Bangalore bypass Highway, NH-4, Pune-411021, Maharashtra
Pune
MAHARASHTRA |
7030810110
akc@cdi.org.in |
| Dr Deepak Maheshwari |
Department of Endocrinology, SMS Hospital |
J.L.N. Marg, Jaipur, Rajasthan - 302004 India
Jaipur
RAJASTHAN |
9829010252
drdeepakmaheshwari@gmail.com |
| Dr Sanjeev Kumar Sidana |
Eternal Hospital, Unit of Eternal Heart Care Centre and Research Institute Private Limited |
3A, Jagatpura Road, Near Jawahar Circle, Jaipur-302017, Rajasthan,
India
Jaipur
RAJASTHAN |
919928202456
sidanasanjeev@rediffmail.com |
| Dr Prashanth Kumar |
Karnataka Institute of Medical Sciences |
PB Road, Vidya Nagar, Hubli-580022, Karnataka, India
Dharwad
KARNATAKA |
918217356417
drprashanthm.kims@gmail.com |
| Dr Prasad M Bhat |
Lifecare Hospital And Research Centre |
2748-2152, M.L.N Enclave, 16th E CrossRoad, 8th Main, D-Block Next to Corportion Bank, Sahakarnagar
Bangalore Bengaluru Urban Karnataka - 560092 India
Bangalore
KARNATAKA |
7349570035
drprasadlcrc@gmail.com |
| Dr Atul Damodar Abhyankar |
Nirmal Hospital Private Limited |
Ring Road, Surat-395002, Gujarat, India
Surat
GUJARAT |
9825145738
atulda@hotmail.com |
| Dr Dipak Ranjan Das |
SCB Medical College and Hospitals |
Behera Colony, Cuttack, Odisha, India, 753001
Cuttack
ORISSA |
9437165904
maildrdipak@gmail.com |
| Dr Charan Lanjewar |
Seth G.S. Medical College and KEM Hospital |
Department of Endocrinology, Seth G.S. Medical College and KEM Hospital, Acharya Donde Marg, Parel, Mumbai – 400012
Mumbai
MAHARASHTRA |
2224107595
charanlanjewar@kem.edu |
| Dr Sandarbh Piyushkumar Patel |
Sheth Vadilal Sarabhai General Hospital |
Madalpur, Gam, Paldi, Road, Ellisbridge, Ahmedabad, Gujarat-380006
Ahmadabad
GUJARAT |
9909031385
drsandarbh.cardio@gmail.com |
| Dr Divya Prakash |
Victoria Hospital, Bangalore Medical College and Research Institute |
K R Road, Room 322, 3rd Floor, OPD Block, Victoria Hospital,BMCRI,
Bangalore, Karnataka, India, 560002
Bangalore
KARNATAKA |
9113030135
drdivyaprakashbmc@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 12 |
| Name of Committee |
Approval Status |
| Chellaram Diabetes Institute Ethics Committee |
Submittted/Under Review |
| Eternal Heart Care Centre and Research Institute - Institutional Ethics Committee |
Approved |
| Ethics Committee of Bangalore Medical College and Research Institute |
Approved |
| Ethics Committee, S.M.S. Medical College and Attached Hospitals |
Submittted/Under Review |
| IEC Rughwani Child Care Centre and Hospital |
Approved |
| Institutional Ethics Committee Excelcare Hospitals |
Approved |
| Institutional Ethics Committee S.C.B. Medical College and Hospital Cuttack |
Approved |
| Institutional Ethics Committee, Karnataka Institute of Medical sciences |
Approved |
| Institutional Ethics Committee, Seth G. S. Medical College & K. E. M. Hospital |
Approved |
| Lifecare Hospital Institutional Review Board |
Approved |
| Nirmal Hospital Ethics Committee |
Approved |
| Sangini Hospital, Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: E11||Type 2 diabetes mellitus, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Insulin Glargine |
Starting dose of Insulin Glargine of 10 IU/day SC. Doses will be individualized and titrated according to a treat-to-target algorithm. The study will last about 104 weeks. |
| Intervention |
LY3502970 or Orforglipron |
Starting dose of LY3502970 of 1mg QD orally for 4 weeks, followed by increases in dose every 4 weeks up to 36mg QD orally. The study will last about 104 weeks. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1. Have been diagnosed with type 2 diabetes mellitus (T2DM)
2. Are at least 18 years of age or legal age of consent in the jurisdiction in which the study is taking place, whichever is older.
3. Have HbA1c at screening of ≥7.0% and ≤10.5% if background diabetes medication does not include a sulfonylurea, or ≥7.5% and ≤10.5% if background diabetes medication includes a sulfonylurea.
4. Are on stable treatment of at least 1 and no more than 3 oral antihyperglycemic drugs for at least 90 days before screening. Antihyperglycemic drugs may include metformin, SGLT-2 inhibitors, and/or sulfonylureas
5. Have increased risk for cardiovascular (CV) events due to: Coronary heart disease, Peripheral arterial disease, presumed to be of atherosclerotic origin, Cerebrovascular disease, presumed to be of atherosclerotic origin, Chronic kidney disease (CKD), Congestive heart failure (CHF) New York Heart Association (NYHA) functional classification II to III
6. Are of stable weight (± 5%) for at least 90 days prior to screening
7. Have a BMI ≥25 kilograms per meter squared (kg/m2) at screening |
|
| ExclusionCriteria |
| Details |
1. Have type 1 diabetes mellitus
2. Have had chronic or acute pancreatitis any time prior to screening
3. Currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema (e.g. laster photocoagulation or intravitreal injections of anty-VEGF inhibitors
4. Have a known clinically significant gastric emptying abnormality
5. Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) or aspartate aminotransferase (AST) enzyme level ≥5.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory
6. Have had any of the following within 60 days prior to screening: acute myocardial infarction, cerebrovascular accident (stroke), or hospitalization for congestive heart failure
7. Have an eGFR <15 mL/min/1.73 m2 as determined at screening
8. Have a family (first-degree relative) or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
9. Have been taking any other diabetes medicines other than metformin, SGLT-2 inhibitors, and/or sulfonylureas during the last 90 days
10. Have used any weight loss drugs, including herbal or nutritional supplements, within 90 days of screening |
|
|
Method of Generating Random Sequence
|
Stratified randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Time to First Occurrence of Any Major Adverse Cardiovascular Event (MACE-4) [Myocardial Infarction (MI), Stroke, Hospitalization for Unstable Angina, or Cardiovascular (CV) Death] |
Baseline to End of the Study (Approximate Maximum 104 Weeks) |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Time to First Occurrence of Any MACE-3 Event (MI, Stroke, or CV death) |
Baseline to End of the Study (Approximately 104 Weeks) |
1. Change from Baseline in HbA1c
2. Change from Baseline in Fasting Serum Glucose
3. Change from Baseline in Daily Average 7-point SMBG
4. Change from Baseline in Body Weight
5. Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Score |
Baseline, Week 52 |
| Pharmacokinetics (PK): Plasma Serum Concentrations of Orforglipron |
Baseline through Week 52 |
1. Percentage of Participants with HbA1c Target Values Less Than 7.0% (53 mmol/mol)
2. Percent Change from Baseline Body Weight |
Week 52 |
|
|
Target Sample Size
|
Total Sample Size="2620"
Sample Size from India="120"
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)
|
30/10/2023 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
03/04/2023 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="10"
Days="25" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - YES
- What data in particular will be shared?
Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
- What additional supporting information will be shared?
Response - Study Protocol
Response - Statistical Analysis Plan
Response - Clinical Study Report
- Who will be able to view these files?
Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
- For what types of analyses will this data be available?
Response - For individual participant data meta-analysis.
- By what mechanism will data be made available?
Response (Others) - www.vivli.org
- For how long will this data be available start date provided 01-10-2023 and end date provided 31-03-2024?
Response - Beginning 3 months and ending 5 years following article publication.
- Any URL or additional information regarding plan/policy for sharing IPD?
Additional Information - NIL
|
|
Brief Summary
|
The main purpose of this study is to determine safety and efficacy of orforglipron compared with insulin glargine in participants with type 2 diabetes and obesity or overweight at increased cardiovascular risk. The study will last approximately 2 years may include up to 27 visits.
Remarks: CT-NOC conditional approval was provided for protocol J2A-MC-GZGS with one of the conditions outlined being that the Principal investigator (PI) should be cardiologist and Co-Investigator (Co-I) should be endocrinologist in each site in the proposed study. Thus, to comply with this condition, PI for all sites have been changed to cardiologists with previous encrocrinologists having their role switched to Co-I. These individual site PI change requests have been notified to respective site ECs and to the DCGI. Thus, the PI’s listed in this CTRI application are the updated cardiologists that will function as the PI of these sites for the J2A-MC-GZGS study. |