Clinical Trials List
Protocol NumberI8B-MC-ITRN
NCT Number(ClinicalTrials.gov Identfier)NCT03214380
2017-08-01 - 2019-01-31
Phase III
Terminated5
ICD-10E11.8
Type 2 diabetes mellitus with unspecified complications
A Prospective, Randomized, Double-Blind Comparison of LY900014 to Insulin Lispro, Both in Combination with Insulin Glargine or Insulin Degludec in Adults with Type 2 Diabetes PRONTO-T2D
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Trial Applicant
ELI LILLY AND COMPANY(TAIWAN), INC.
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Sponsor
lily
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Jia-Hong Lin Division of Endocrinology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chung-Huei Hsu Division of Endocrinology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Type 2 Diabetes
Objectives
Primary Objective:
1. To test the hypothesis that LY900014 is
noninferior to insulin lispro on glycemic control
(non-inferiority margin [NIM]=0.4% for
hemoglobin A1c [HbA1c]) in patients with
T2D, when administered as prandial insulin
(0 to 2 minutes prior to the meal), in
combination with basal insulin glargine or
insulin degludec for 26 weeks
Secondary Objectives:
1. To test the hypothesis that LY900014 is superior
to insulin lispro in controlling 1-hour
postprandial glucose (PPG) excursions, when
administered as prandial insulin
2. To test the hypothesis that LY900014 is superior
to insulin lispro in controlling 2-hour PPG
excursions when administered as prandial
insulin
3. To test the hypothesis that LY900014 is superior
to insulin lispro on improving glycemic control
(HbA1c) when administered as prandial insulin
4. To compare LY900014 and insulin lispro with
respect to the rate of severe hypoglycemic
events
5. To compare LY900014 and insulin lispro with
respect to the incidence and rate of documented
symptomatic postmeal hypoglycemia
6. To compare LY900014 and insulin lispro with
respect to the incidence and rate of documented
symptomatic hypoglycemia
7. To compare LY900014 and insulin lispro with
respect to 1,5-Anhydroglucitol (1,5-AG)
8. To compare LY900014 and insulin lispro with
respect to 10-point self-monitored blood glucose
(SMBG) profiles
9. To compare LY900014 and insulin lispro with
respect to total, basal, and prandial insulin dose
10. To compare LY900014 and insulin lispro with
respect to diabetes treatment satisfaction as
measured by the Insulin Treatment Satisfaction
Questionnaire (ITSQ)
11. To compare LY900014 and insulin lispro with
respect to the proportion of patients achieving
HbA1c targets
Test Drug
LY900014
Active Ingredient
LY900014
Dosage Form
Injection
Dosage
3 ml
Endpoints
1. Difference between LY900014 and insulin
lispro in change from baseline to Week 26 in
HbA1c
2. 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 an
MMTT at Week 26
3. 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 test at Week 26
4. Difference between LY900014 and insulin
lispro in change from baseline to Week 26 in
HbA1c
5. Rate (events/patient/100 years) of severe
hypoglycemic events from baseline through
Week 26
6. Rate (events/patient/year and/or
events/patient/30 days) and incidence (percent
of patients with at least 1 event) of documented
symptomatic postmeal hypoglycemia within 1
and 2 hours after start of a meal from baseline
through Week 26
7. Rate (events/patient/year and/or
events/patient/30 days) and incidence (percent
of patients with at least 1 event) of documented
symptomatic hypoglycemic events from
baseline through Week 26
8. Change from baseline 1,5-AG values at
Week 26
9. Change from baseline 10-point SMBG values
at Week 26
10. Change from baseline in total, basal and
prandial insulin dose and prandial/total insulin
dose ratio at Week 26
10. Change from baseline in total, basal and
prandial insulin dose and prandial/total insulin
dose ratio at Week 26
11. Change from baseline ITSQ regimen
inconvenience and lifestyle flexibility domain
scores at Week 26
12. The proportion of patients with HbA1c <7%
and ≤6.5% at Week 26
lispro in change from baseline to Week 26 in
HbA1c
2. 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 an
MMTT at Week 26
3. 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 test at Week 26
4. Difference between LY900014 and insulin
lispro in change from baseline to Week 26 in
HbA1c
5. Rate (events/patient/100 years) of severe
hypoglycemic events from baseline through
Week 26
6. Rate (events/patient/year and/or
events/patient/30 days) and incidence (percent
of patients with at least 1 event) of documented
symptomatic postmeal hypoglycemia within 1
and 2 hours after start of a meal from baseline
through Week 26
7. Rate (events/patient/year and/or
events/patient/30 days) and incidence (percent
of patients with at least 1 event) of documented
symptomatic hypoglycemic events from
baseline through Week 26
8. Change from baseline 1,5-AG values at
Week 26
9. Change from baseline 10-point SMBG values
at Week 26
10. Change from baseline in total, basal and
prandial insulin dose and prandial/total insulin
dose ratio at Week 26
10. Change from baseline in total, basal and
prandial insulin dose and prandial/total insulin
dose ratio at Week 26
11. Change from baseline ITSQ regimen
inconvenience and lifestyle flexibility domain
scores at Week 26
12. The proportion of patients with HbA1c <7%
and ≤6.5% at Week 26
Inclution Criteria
[1] Men or women diagnosed (clinically) with T2D, based on the World Health Organization (WHO) classification (Appendix 5) for at least 1 year prior to screening
Patient Characteristics
[2] Are at least 20 years of age
[3] Have been treated for at least 90 days prior to screening with:
a) Basal insulin (insulin glargine U-100 [Basaglar/Abasaglar or LANTUS] or U-300, insulin detemir, insulin degludec U-100 or U-200, or NPH insulin) in combination with at least 1 prandial injection of bolus insulin (insulin lispro U-100 or U-200, insulin aspart, insulin glulisine, or regular insulin)
Or
b) Premixed analog or human insulin regimens with any basal and bolus insulin combination injected at least twice daily
[4] Patients may be treated with up to 3 of the following OAMs in accordance with local regulations:
• Metformin
• Dipeptidyl peptidase-4 (DPP-4) inhibitor
• Sodium glucose cotransporter 2 (SGLT2) inhibitor
• Sulfonylurea
• Meglitinide
• Alpha-glucoside inhibitor
Doses of OAMs are required to have been stable for at least 90 days prior to screening. Combination medications (2 or more medications in 1 pill) should be counted as the number of individual components.
During the study lead-in and treatment periods, patients may continue the use of up to 2 of the following OAMs: metformin, SGLT2 inhibitor. Other prestudy OAMs will be discontinued at the beginning of the lead-in period. Please also refer to management of OAMs in Section 7.7.1.
[5] Have an HbA1c value between ≥7.0 and ≤10.0%, according to the central laboratory at the time of screening (Visit 1).
[6] Have a body mass index (BMI) of ≤45.0 kg/m2 at screening (Visit 1).
[7] Male patients:
a) No male contraception required except in compliance with specific local government study requirements.
[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 – 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 follicle-stimulating 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 (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/communications, and have access to a reliable cellular signal for transmission of the electronic clinical outcomes assessment (eCOA) data
[10] Have refrigeration in the home or have ready access to refrigeration for storage of insulin therapy
[11] Patient for 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.
[12] 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
c) Keep records in an 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 a suggested algorithm for basal and prandial insulin dose adjustment as agreed upon with the investigator
f) Comply with the use of the study insulin and scheduled visits
[13] Considered healthy (apart from T2D) upon completion of medical history, physical examination, vital signs, electrocardiogram (ECG), and analysis of laboratory safety variables, as judged by the investigator
Informed Consent
[14] Have given written informed consent to participate in this study in accordance with local regulations.
Patient Characteristics
[2] Are at least 20 years of age
[3] Have been treated for at least 90 days prior to screening with:
a) Basal insulin (insulin glargine U-100 [Basaglar/Abasaglar or LANTUS] or U-300, insulin detemir, insulin degludec U-100 or U-200, or NPH insulin) in combination with at least 1 prandial injection of bolus insulin (insulin lispro U-100 or U-200, insulin aspart, insulin glulisine, or regular insulin)
Or
b) Premixed analog or human insulin regimens with any basal and bolus insulin combination injected at least twice daily
[4] Patients may be treated with up to 3 of the following OAMs in accordance with local regulations:
• Metformin
• Dipeptidyl peptidase-4 (DPP-4) inhibitor
• Sodium glucose cotransporter 2 (SGLT2) inhibitor
• Sulfonylurea
• Meglitinide
• Alpha-glucoside inhibitor
Doses of OAMs are required to have been stable for at least 90 days prior to screening. Combination medications (2 or more medications in 1 pill) should be counted as the number of individual components.
During the study lead-in and treatment periods, patients may continue the use of up to 2 of the following OAMs: metformin, SGLT2 inhibitor. Other prestudy OAMs will be discontinued at the beginning of the lead-in period. Please also refer to management of OAMs in Section 7.7.1.
[5] Have an HbA1c value between ≥7.0 and ≤10.0%, according to the central laboratory at the time of screening (Visit 1).
[6] Have a body mass index (BMI) of ≤45.0 kg/m2 at screening (Visit 1).
[7] Male patients:
a) No male contraception required except in compliance with specific local government study requirements.
[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 – 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 follicle-stimulating 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 (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/communications, and have access to a reliable cellular signal for transmission of the electronic clinical outcomes assessment (eCOA) data
[10] Have refrigeration in the home or have ready access to refrigeration for storage of insulin therapy
[11] Patient for 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.
[12] 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
c) Keep records in an 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 a suggested algorithm for basal and prandial insulin dose adjustment as agreed upon with the investigator
f) Comply with the use of the study insulin and scheduled visits
[13] Considered healthy (apart from T2D) upon completion of medical history, physical examination, vital signs, electrocardiogram (ECG), and analysis of laboratory safety variables, as judged by the investigator
Informed Consent
[14] Have given written informed consent to participate in this study in accordance with local regulations.
Exclusion Criteria
[15] Having any other condition (including known drug or alcohol abuse, psychiatric disorder including eating disorder) that precludes the patient from following and completing the protocol
[16] Have been diagnosed, at any time, with T1D or Latent Autoimmune Diabetes in Adults
[17] Have hypoglycemia unawareness as judged by the investigator
[18] Have had any episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within the 6 months prior to screening
[19] Have had 1 or more episodes of diabetic ketoacidosis or hyperglycemic hyperosmolar state within the 6 months prior to screening
[20] Have a known diagnosis of secondary diabetes (for example, diabetes caused by hemochromatosis, acromegaly, chronic pancreatitis, or pancreatectomy)
[21] Excessive insulin resistance defined as having received a total daily dose of insulin >2.0 U/kg at the time of screening
[22] Have a history of or are being evaluated for bariatric surgery including Roux en Y gastric bypass surgery, gastric banding, and/or gastric sleeve
[23] 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 (Appendix 6), myocardial infarction, unstable angina pectoris or coronary arterial bypass graft
[24] Renal:
a) History of renal transplantation
b) Currently receiving renal dialysis
c) Serum creatinine >2.0 mg/dL (177 µmol/L) at screening
[25] Hepatic: Have obvious clinical signs or symptoms of liver disease (for example, acute or chronic hepatitis or cirrhosis), or elevated liver enzyme measurements as indicated below at screening:
a) Total bilirubin level (TBL) ≥2Xthe 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
[26] 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
[27] Having any hypersensitivity or allergy to any of the insulins or excipients used in this trial
[28] Having hypersensitivity or allergy to the ingredients in the standardized test meal (for example, nut allergy)
[29] 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
[30] Have presence of clinically significant gastrointestinal disease (for example, clinically active gastroparesis associated with wide glucose fluctuations) in the investigator’s opinion
Prior/Concomitant Therapy
[31] Have used thiazolidinediones, GLP-1 receptor agonist, or pramlintide within 90 days prior to screening
[32] Have used insulin human inhalation powder (Afrezza®) within 90 days prior to screening
[33] Have used CSII within 90 days prior to screening
[34] Glucocorticoid therapy: receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (including IV, intramuscular, SC, or oral, but excluding topical, intraocular, intranasal, intra-articular and inhaled preparations) or have received such therapy within 8 weeks immediately prior to screening with the exception of replacement therapy for adrenal insufficiency
[35] Have used any weight loss drugs (for example, prescription drugs: liraglutide, lorcaserin, orlistat, phentermine, phentermine/topiramate, naltrexone/bupropion; or over-the-counter weight loss medications) within 90 days prior to screening
Prior/Concurrent Clinical Trial Experience
[36] Are currently enrolled in any other clinical trial involving an IP or any other type of medical research judged not to be scientifically or medically compatible with this study
[37] Have participated, within the last 30 days in a clinical trial involving an IP. If the previous IP has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed
[38] Have previously completed or withdrawn from this study after having signed the informed consent form (ICF) or any other study investigating LY900014 after receiving at least 1 dose of the IP
Other Exclusions
[39] Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted
[40] Are Lilly employees or representative (including employees, temporary contract workers, or designees responsible for the conduct of the study)
[41] Are unable and/or unwilling to provide informed consent, to make themselves available for the duration of the study, or to abide by study procedures
[16] Have been diagnosed, at any time, with T1D or Latent Autoimmune Diabetes in Adults
[17] Have hypoglycemia unawareness as judged by the investigator
[18] Have had any episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within the 6 months prior to screening
[19] Have had 1 or more episodes of diabetic ketoacidosis or hyperglycemic hyperosmolar state within the 6 months prior to screening
[20] Have a known diagnosis of secondary diabetes (for example, diabetes caused by hemochromatosis, acromegaly, chronic pancreatitis, or pancreatectomy)
[21] Excessive insulin resistance defined as having received a total daily dose of insulin >2.0 U/kg at the time of screening
[22] Have a history of or are being evaluated for bariatric surgery including Roux en Y gastric bypass surgery, gastric banding, and/or gastric sleeve
[23] 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 (Appendix 6), myocardial infarction, unstable angina pectoris or coronary arterial bypass graft
[24] Renal:
a) History of renal transplantation
b) Currently receiving renal dialysis
c) Serum creatinine >2.0 mg/dL (177 µmol/L) at screening
[25] Hepatic: Have obvious clinical signs or symptoms of liver disease (for example, acute or chronic hepatitis or cirrhosis), or elevated liver enzyme measurements as indicated below at screening:
a) Total bilirubin level (TBL) ≥2Xthe 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
[26] 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
[27] Having any hypersensitivity or allergy to any of the insulins or excipients used in this trial
[28] Having hypersensitivity or allergy to the ingredients in the standardized test meal (for example, nut allergy)
[29] 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
[30] Have presence of clinically significant gastrointestinal disease (for example, clinically active gastroparesis associated with wide glucose fluctuations) in the investigator’s opinion
Prior/Concomitant Therapy
[31] Have used thiazolidinediones, GLP-1 receptor agonist, or pramlintide within 90 days prior to screening
[32] Have used insulin human inhalation powder (Afrezza®) within 90 days prior to screening
[33] Have used CSII within 90 days prior to screening
[34] Glucocorticoid therapy: receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (including IV, intramuscular, SC, or oral, but excluding topical, intraocular, intranasal, intra-articular and inhaled preparations) or have received such therapy within 8 weeks immediately prior to screening with the exception of replacement therapy for adrenal insufficiency
[35] Have used any weight loss drugs (for example, prescription drugs: liraglutide, lorcaserin, orlistat, phentermine, phentermine/topiramate, naltrexone/bupropion; or over-the-counter weight loss medications) within 90 days prior to screening
Prior/Concurrent Clinical Trial Experience
[36] Are currently enrolled in any other clinical trial involving an IP or any other type of medical research judged not to be scientifically or medically compatible with this study
[37] Have participated, within the last 30 days in a clinical trial involving an IP. If the previous IP has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed
[38] Have previously completed or withdrawn from this study after having signed the informed consent form (ICF) or any other study investigating LY900014 after receiving at least 1 dose of the IP
Other Exclusions
[39] Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted
[40] Are Lilly employees or representative (including employees, temporary contract workers, or designees responsible for the conduct of the study)
[41] Are unable and/or unwilling to provide informed consent, to make themselves available for the duration of the study, or to abide by study procedures
The Estimated Number of Participants
-
Taiwan
70 participants
-
Global
833 participants
