Comparison of LY900014 to Insulin Lispro in Adults with Type 1 Diabetes

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/09/009591
• Date of registration: 01-09-2017
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company India Pvt Ltd
• Public title: Comparison of LY900014 to Insulin Lispro in Adults with Type 1 Diabetes
• Scientific title: Protocol I8B-MC-ITRM: A Prospective, Randomized, Double-Blind Comparison of LY900014 to Insulin Lispro with an Open-Label Postprandial LY900014 Treatment Group, in Combination with Insulin Glargine or Insulin Degludec, in Adults with Type 1 Diabetes
• Date of first enrolment: 07-09-2017
• Target sample size: 1199
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19597
• Study type: Interventional
• Study design: Randomized, Parallel Group, Active Controlled Trial; Method of generating randomization sequence:Stratified randomization Method of allocation concealment:Centralized Blinding and masking:Participant and Investigator Blinded
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Brazil, Germany, Greece, India, Italy, Japan, Mexico, New Zealand, Poland, Romania, Russian Federation, Slovakia, Spain, Sweden, Taiwan, United States of America

Contacts

• Name: Dr Rajeev Sharan Shrivastava
• Affiliation: Eli Lilly and Company (India) Pvt. Ltd.

• Name: Dr Rohit Arora
• Affiliation: Eli Lilly and Company (India) Pvt. Ltd.

Key inclusion & exclusion criteria

Inclusion criteria: 1. Men or women diagnosed (clinically) with T1D, based on the(WHO) classification (Appendix 5) for at least 1 year prior to screening, and continuously using insulin for at least 1 year

2. Are at least 18 years of age

3. Have been on MDI therapy including a rapid acting insulin analog (insulin lispro U-100, insulin aspart, insulin glulisine) for at least 90 days

4. Have been treated for at least 30 days prior to screening with one of the following:

a) Insulin glargine U-100 or U-300

b) Insulin detemir U-100

c) Insulin degludec U-100 or U-200

d) NPH

5. Have an HbA1c value >=7.0 and <=9.5%, according to the central laboratory at

screening (Visit 1).

6. Have a body mass index (BMI) of <=35.0 kg/m2 at screening (Visit 1).

7. Male patients:

a) No male contraception required except in compliance with specific local

government study

8. Female patients:

a) Women not of childbearing potential may participate and include those who are:

i) infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as Mullerian agenesis;

Or

ii) postmenopausal â?? defined as either

(1) a woman 50 to 54 years of age (inclusive) with an intact uterus, not

on hormone therapy who has had either

(a) cessation of menses for at least 1 year;

Or

(b) at least 6 months of spontaneous amenorrhea with a folliclestimulating

hormone >40 mIU/mL;

Or

(2) a woman 55 or older not on hormone therapy, who has had at least

6 months of spontaneous amenorrhea;

Or

(3) a woman at least 55 years of age with a diagnosis of menopause

prior to starting hormone replacement therapy

b) Women of childbearing potential participating:

i) Cannot be pregnant or intend to become pregnant

ii) Cannot be breastfeeding (including the use of a breast pump)

iii) Must remain abstinent or use 1 highly effective method of contraception

or a combination of 2 effective methods of contraception for the entirety

of the study (See Appendix 7)

iv) Test negative for pregnancy at the time of screening (Visit 1). Note: a urine pregnancy test is conducted at Visit 8.

9.Have access to a telephone or alternative means for close monitoring and

communications, and have access to a reliable cellular signal for transmission of

the electronic clinical outcomes assessment (eCOA) data

10.Patient whom the investigator has determined can be randomized and maintain

the treatment regimens based on their previous medical history including insulin

dosing regimens, hypoglycemic episodes, and glycemic control

11.Capable of, willing, and desirous to do the following:

a) Inject insulin with the use of an insulin injection device (insulin pen)

according to included directions

b) Perform self-BG monitoring including 10-point SMBG on designated days

(patients using a personal CGM device for insulin dosing decisions must

still perform the SMBG per protocol)

c) Keep records in eCOA as required by this protocol

d) Participate in two 4-hour mixed-meal tolerance tests (MMTTs) and consume

a standardized meal for the tests

e) Follow an algorithm for basal insulin adjustment and individualized prandial

insulin dosi
Exclusion criteria: 1.Have any other condition (including known drug or alcohol abuse, or psychiatric disorder including eating disorder) that precludes the patient from following and completing the protocol

2. Have hypoglycemia unawareness as judged by the investigator

3. Have had more than 1 episode of severe hypoglycemia (defined as requiring

assistance due to neurologically disabling hypoglycemia) within the last6 months prior to screening

4. Have had more than 1 emergency room visit or hospitalization due to poor glucose control (hyperglycemia or diabetic ketoacidosis) within 6 months prior to screening (Visit 1)

5. Have cardiovascular disease within the last 6 months prior to screening, defined

as stroke, decompensated heart failure New York Heart Association class III or

IV (see Appendix 6), myocardial infarction, unstable angina pectoris, or

coronary arterial bypass graft

6. Renal:

a) History of renal transplantation

b) Currently receiving renal dialysis

c) Serum creatinine >2.0 mg/dL (177 μmol/L) at screening

7.symptoms of liver disease (for

example, acute or chronic hepatitis, or cirrhosis) or elevated liver enzyme

measurements as indicated below at screening (Visit 1):

a) Total bilirubin level (TBL) >=2X the upper limit of normal (ULN) (with the

exception of Gilberts Disease) as defined by the central laboratory,

OR

b) Alanine aminotransferase (ALT) >=3X ULN as defined by the central

laboratory

OR

c) Aspartate aminotransferase (AST) >=3X ULN as defined by the central

laboratory

8. Malignancy: Have active or untreated malignancy, have been in remission from

clinically significant malignancy (other than basal cell or squamous cell skin

cancer) for less than 5 years, or are at an increased risk for developing cancer or

a recurrence of cancer in the opinion of the investigator

9. Have any hypersensitivity or allergy to any of the insulins or excipients used in

this trial

10. Have hypersensitivity or allergy to any of the ingredients in the standardized

test meal (MMTT) (for example, nut allergy)

11. Hematologic: Have had a blood transfusion or severe blood loss within 90 days

prior to screening or have known hemoglobinopathy, anemia, or any other traits

known to interfere with measurement of HbA1c

12. Have presence of clinically significant gastrointestinal disease (for example,

clinically active gastroparesis associated with wide glucose fluctuations) in the

investigatorâ??s opinion

13.Have excessive insulin resistance defined as having received a total daily dose

of insulin >1.5 U/kg at the time of screening





Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Type 1 diabetes Health Condition 2: E109- Type 1 diabetes mellitus without complications

Intervention(s)

Intervention1: LY900014- Ultra Rapid Insulin: The aim of this study is to demonstrate that an ultra-rapid formulation of insulin lispro, LY900014, is noninferior to
insulin lispro on glycemic control as measured by change from baseline to Week 26 in hemoglobin A1c (HbA1c) in
patients with T1D when administered in a double-blind manner as prandial insulin in combination with basal insulin
glargine or insulin degludec.
Control Intervention1: Insulin Lispro: Rapid-acting insulins, such as Humalog®, have been shown to have a more rapid onset of action compared to
human insulin; however, the general consensus is that they are not rapid enough to match carbohydrate absorption,
whether delivered by pump or syringe/pen injector, limiting efficacy. An ultra-rapid-acting prandial insulin that
would shift the pharmacokinetic (PK) and glucodynamic profiles of insulin to provide an even faster onset of action
would better match carbohydrate absorption and allow for efficacious dosing immediately prior to meals or even
after meals. Ultra-rapid insulin (URI) could be useful in the treatment of type 1 diabetes (T1D) and type 2 diabetes
(T2D) in adults and children when given by multiple daily injections (MDI) or by continuous subcutaneous insulin
infusion (CSII).

Primary Outcome(s)

To test the hypothesis that LY900014 is non-inferior to Insulin Lispro on glycemic control in patient with T1DTimepoint: Difference between LY900014 and insulin lispro

in change from baseline to Week 26 in HbA1c

Secondary Outcome(s)

To test the hypothesis that LY900014 is superior

to insulin lispro on improving glycemic control

(HbA1c) when administered as prandial insulinTimepoint: Difference between LY900014 and insulin lispro

in change from baseline to Week 26 in HbA1c

To test the hypothesis that LY900014 is superior

to insulin lispro in controlling 1-hour postprandial

glucose (PPG) excursions, when administered as

prandial insulinTimepoint: Difference between LY900014 and insulin lispro

in the 1-hour PPG excursion (serum glucose

measured 1 hour after the start of the meal minus

fasting serum glucose) from a mixed-meal

tolerance test (MMTT) at Week 26

To test the hypothesis that LY900014 is superior

to insulin lispro in controlling 2-hour PPG

excursions, when administered as prandial insulinTimepoint: Difference between LY900014 and insulin lispro

in the 2-hour PPG excursion (serum glucose

measured 2 hours after the start of the meal minus

fasting serum glucose) from an MMTT at

Week 26

Secondary ID(s)

Protocol I8B-MC-ITRM dated 16-Feb-2017

Source(s) of Monetary Support

Eli Lilly and Company (India) PVT LTD, Plot No. 92, Sector-32, Gurgaon, Haryana - 122001

Ethics review

Status: Approved
Approval date: 15/05/2017
Contact:

Ethics Committe of Diabetes Thyroid Hormone research institute

Status: Approved
Approval date: 15/05/2017
Contact:

Medilink Ethics Committee

Status: Approved
Approval date: 30/05/2017
Contact:

Institutional Ethics Committee, Ramdevrao Hospital

Status: Approved
Approval date: 29/06/2017
Contact:

Ethics Committee, MS Ramaiah medical college and hospital

Status: Approved
Approval date: 01/07/2017
Contact:

Thakershy Charitable Trust Ethics Committee

Status: Approved
Approval date: 07/07/2017
Contact:

Institutional Ethics Committee, Care Foundation

Status: Approved
Approval date: 27/07/2017
Contact:

Jehangir clinical development centre Institutional Review Board

Status: Approved
Approval date: 31/07/2017
Contact:

Institutional Ethics Committee, Poona medical research foundation

Status: Approved
Approval date: 12/08/2017
Contact:

Institutional Ethics Committe, Care Convergence Centre

Status: Approved
Approval date: 23/08/2017
Contact:

Institutional Ethics Committee, B J Medical college and Hospital

Status: Approved
Approval date: 01/09/2017
Contact:

Institutional Ethics Committe, Gandhi Medical College

Status: Approved
Approval date: 19/09/2017
Contact:

Institutional Ethics Committee, King George Hospital

Status: Approved
Approval date: 27/09/2017
Contact:

Ethics committee of Manipal Hospital

Results

• Date Completed: 30/06/2019