A Study of LY3209590 in Participants With Type 2 Diabetes Mellitus

• ClinicalTrials.gov Identifier: NCT03736785
• Recruitment Status: Completed
• First Posted: November 9, 2018
• Results First Posted: March 8, 2021
• Last Update Posted: March 8, 2021
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: November 2, 2018
• First Posted Date: November 9, 2018
• Results First Submitted Date: February 12, 2021
• Results First Posted Date: March 8, 2021
• Last Update Posted Date: March 8, 2021
• Actual Study Start Date: November 15, 2018
• Actual Primary Completion Date: February 18, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 12, 2021)

Change From Baseline in HbA1c [ Time Frame: Baseline, Week 32 ]

HbA1c is the glycosylated fraction of haemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Change from baseline in HbA1c was analysed by mixed model repeated measures (MMRM) including fixed effects of treatment, stratification factors (country, BMI group [> 30 or ≤ 30], sulfonylureas use at study entry), visit and treatment by visit interaction and baseline HbA1c as the covariate.

Original Primary Outcome Measures (submitted: November 8, 2018)

Change from Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, Week 32 ]

Change from baseline in HbA1c

Current Secondary Outcome Measures (submitted: February 12, 2021)

• Change From Baseline in HbA1c Compared to Insulin Degludec [ Time Frame: Baseline, Week 32 ]
  HbA1c is the glycosylated fraction of haemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Change from baseline in HbA1c was analysed by MMRM including fixed effects of treatment, stratification factors (country, BMI group [> 30 or ≤ 30], sulfonylureas use at study entry), visit and treatment by visit interaction, and baseline HbA1c as the covariate.
• Change From Baseline in Fasting Glucose [ Time Frame: Baseline, Week 32 ]
  Change from baseline in fasting glucose was analysed by MMRM including fixed effects of treatment, stratification factors (country, BMI group [> 30 or ≤ 30], sulfonylureas use at study entry, HbA1c strata [<8.5% or ≥8.5%]), visit and treatment by visit interaction, and baseline fasting glucose as the covariate.
• Change From Baseline in Insulin Dose (LY3209590) [ Time Frame: Week 1, Week 32 ]
  The baseline for both LY3209590 arms was the first regular weekly dose at Week 1.
• Change From Baseline in Insulin Dose (Insulin Degludec) [ Time Frame: Baseline, Week 32 ]
  Change from Baseline in Insulin Dose for Insulin Degludec arm was reported.
• Rate of Total Documented Symptomatic Hypoglycemia [ Time Frame: Baseline through week 32 ]
  The hypoglycemia events were defined by participant reported events with glucose ≤54 mg/dL (3.0 millimole per liter (mmol/L)). Relative Rate was calculated based on Group Mean. Group Mean was estimated by first taking the inverse link function on individual patient covariates, then averaging over all participants.
• Change From Baseline in Body Weight [ Time Frame: Baseline, Week 32 ]
  Change from baseline in body weight was analysed by MMRM including fixed effects of treatment, visit and treatment by visit interaction, and baseline body weight as the covariate.
• Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3209590 [ Time Frame: Week 32 ]
  PK: AUC of LY3209590 was reported for LY3209590 Algorithm 1 and LY3209590 Algorithm 2 arms. AUC was calculated for individual participants using the participant's Week 32 LY3209590 dose amount and the participant's estimated clearance value.

Original Secondary Outcome Measures (submitted: November 8, 2018)

• Change from Baseline in HbA1c Compared to Insulin Degludec [ Time Frame: Baseline, Week 32 ]
  Change from baseline in HbA1c compared to insulin degludec
• Change from Baseline in Fasting Glucose [ Time Frame: Baseline, Week 32 ]
  Change from baseline in fasting glucose
• Change from Baseline in Insulin Dose [ Time Frame: Baseline, Week 32 ]
  Change from baseline in insulin dose
• Rate of Total Documented Symptomatic Hypoglycemia [ Time Frame: Week 32 ]
  Rate of total documented symptomatic hypoglycemia
• Change from Baseline in Body Weight [ Time Frame: Baseline, Week 32 ]
  Change from baseline in body weight
• Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3209590 [ Time Frame: Week 32 ]
  PK: AUC of LY3209590

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of LY3209590 in Participants With Type 2 Diabetes Mellitus
• Official Title: A Phase 2, Randomized, Open-Label Trial to Evaluate the Safety and Efficacy of LY3209590 in Study Participants With Type 2 Diabetes Mellitus Previously Treated With Basal Insulin
• Brief Summary: The reason for this study is to see if the study drug LY3209590 is safe and effective in participants with type 2 diabetes that have already been treated with basal insulin.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Type 2 Diabetes Mellitus

Intervention

• Drug: LY3209590
  Administered SC
• Drug: Insulin Degludec
  Administered SC

Study Arms

• Experimental: LY3209590 Algorithm 1
  Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of <140 milligram per deciliter (mg/dL).
  Intervention: Drug: LY3209590
• Experimental: LY3209590 Algorithm 2
  Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of <120 mg/dL.
  Intervention: Drug: LY3209590
• Active Comparator: Insulin Degludec
  Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C <7%.
  Intervention: Drug: Insulin Degludec

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 12, 2021): 399
• Original Estimated Enrollment (submitted: November 8, 2018): 375
• Actual Study Completion Date: February 18, 2020
• Actual Primary Completion Date: February 18, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Type 2 diabetes mellitus according to the World Health Organization (WHO) criteria treated with basal insulin and up to 3 of the following oral antihyperglycemic medication (OAM):

  • dipeptidyl peptidase-4 (DPP-4) inhibitors
  • sodium-glucose cotransporter (SGLT-2) inhibitors
  • biguanides
  • alpha-glucosidase inhibitors
  • sulfonlyureas
• HbA1c value of 6.5% to 10%, inclusive
• Body mass index (BMI) between 20 and 45 kilograms per meter squared (kg/m2), inclusive

Exclusion Criteria:

• Type 1 diabetes mellitus or latent autoimmune diabetes
• Any episodes of severe hypoglycemia and/or hypoglycemia unawareness within the 6 months prior to screening
• Any of the following cardiovascular (CV) conditions: acute myocardial infarction, New York Heart Association Class III or IV heart failure, or cerebrovascular accident (stroke)
• Acute or chronic hepatitis, or obvious clinical signs or symptoms of any other liver disease
• Estimated glomerular filtration rate (eGFR) <30 milliliters/minute/1.73 m2
• Active or untreated malignancy
• Chronic (>14 days) systemic glucocorticoid therapy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Mexico, Puerto Rico, United States

Administrative Information

• NCT Number: NCT03736785
• Other Study ID Numbers: 17059; I8H-MC-BDCM ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: March 2020