A Study of Orforglipron (LY3502970) in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone (ACHIEVE-1)

• ClinicalTrials.gov Identifier: NCT05971940
• Recruitment Status: Recruiting
• First Posted: August 2, 2023
• Last Update Posted: April 16, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: July 25, 2023
• First Posted Date: August 2, 2023
• Last Update Posted Date: April 16, 2024
• Actual Study Start Date: August 9, 2023
• Estimated Primary Completion Date: April 9, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 28, 2023): Change from Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, Week 40 ]
• Original Primary Outcome Measures (submitted: July 25, 2023): Change from Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: Week 40 ]

Current Secondary Outcome Measures (submitted: October 18, 2023)

• Percentage of Participants with an HbA1c target value of <7.0% (53 mmol/mol) [ Time Frame: Week 40 ]
• Percentage of Participants with an HbA1c target value of ≤6.5% (48 mmol/mol) [ Time Frame: Week 40 ]
• Change from Baseline in Fasting Serum Glucose [ Time Frame: Baseline, Week 40 ]
• Percentage Change from Baseline in Body Weight [ Time Frame: Baseline, Week 40 ]
• Change from Baseline in Body Weight [ Time Frame: Baseline, Week 40 ]
• Change from Baseline in Daily Average 7-point Self-Monitored Blood Glucose (SMBG) [ Time Frame: Baseline, Week 40 ]
• Change from Baseline in Systolic Blood Pressure (SBP) [ Time Frame: Baseline, Week 40 ]
• Change from Baseline in Non-HDL Cholesterol [ Time Frame: Baseline, Week 40 ]
• Percentage Change from Baseline in Triglycerides [ Time Frame: Baseline, Week 40 ]
• Percentage of Participants Who Achieved Weight Loss of ≥5% [ Time Frame: Week 40 ]
• Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Scores [ Time Frame: Baseline, Week 40 ]

Original Secondary Outcome Measures (submitted: July 25, 2023)

• Percentage of Participants with an HbA1c target value of <7.0% (53 mmol/mol) [ Time Frame: Week 40 ]
• Percentage of Participants with an HbA1c target value of ≤6.5% (48 mmol/mol) [ Time Frame: Week 40 ]
• Change from Baseline in Fasting Serum Glucose [ Time Frame: Baseline, Week 40 ]
• Percentage Change from Baseline in Body Weight [ Time Frame: Baseline, Week 40 ]
• Change from Baseline in Body Weight [ Time Frame: Baseline, Week 40 ]
• Change from Baseline in Daily Average 7-point Self-Monitored Blood Glucose (SMBG) [ Time Frame: Baseline, Week 40 ]
• Change from Baseline in Systolic Blood Pressure (SBP) [ Time Frame: Baseline, Week 40 ]
• Change from Baseline in Triglycerides [ Time Frame: Baseline, Week 40 ]
• Percentage of Participants Who Achieved Weight Loss of ≥5% [ Time Frame: Week 40 ]
• Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Scores [ Time Frame: Baseline, Week 40 ]

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

Descriptive Information

• Brief Title: A Study of Orforglipron (LY3502970) in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone
• Official Title: A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once Daily Oral LY3502970 Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone
• Brief Summary: The main purpose of this study is to determine safety and efficacy of orforglipron compared with placebo in adult participants with type 2 diabetes and inadequate glycemic control with diet and exercise alone. The study will last approximately 54 weeks.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Type 2 Diabetes

Intervention

• Drug: Orforglipron
  Administered orally.
  Other Name: LY3502970
• Drug: Placebo
  Administered orally

Study Arms

• Experimental: Orforglipron Dose 1
  Participants will receive orforglipron orally.
  Intervention: Drug: Orforglipron
• Experimental: Orforglipron Dose 2
  Participants will receive orforglipron orally.
  Intervention: Drug: Orforglipron
• Experimental: Orforglipron Dose 3
  Participants will receive orforglipron orally.
  Intervention: Drug: Orforglipron
• Placebo Comparator: Placebo
  Participants will receive placebo orally.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 25, 2023): 520
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 9, 2025
• Estimated Primary Completion Date: April 9, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have Type 2 Diabetes
• Have HbA1c ≥7.0% (53 mmol/mol) to ≤9.5% (80 mmol/mol) despite diet and exercise treatment, as determined by the central laboratory at screening.
• Are naïve to insulin therapy except for gestational diabetes or ≤14 days use for acute treatment and have not used any oral or injectable antihyperglycemic medications during the 90 days preceding screening or between screening and randomization.
• Are of stable weight (±5%) for at least 90 days prior to screening and agree to not initiate an intensive diet or exercise program during the study with the intent of reducing body weight other than the lifestyle and/or dietary measures for diabetes treatment.
• Have a body mass index (BMI) ≥23.0 kilogram/square meter (kg/m²) at screening.

Exclusion Criteria:

• Have Type 1 Diabetes
• Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening, or between screening and randomization.
• Currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema
• Have New York Heart Association functional classification IV congestive heart failure.
• Have acute or chronic pancreatitis

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 1-317-615-4559; ClinicalTrials.gov@lilly.com

• Listed Location Countries: China, India, Japan, Mexico, Puerto Rico, United States

Administrative Information

• NCT Number: NCT05971940
• Other Study ID Numbers: 18564; J2A-MC-GZGT ( Other Identifier: Eli Lilly and Company ); U1111-1290-5157 ( Other Identifier: UTN Number )
• 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 participant 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 European Union (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: http://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 - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: April 2024