A Multiple-Dose Study to Investigate the Bioequivalence of Orforglipron (LY3502970) Capsules and Orforglipron Tablets in Participants With Obesity or Overweight Who Are Otherwise Healthy.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 533
- 试验地点
- 7
- 主要终点
- Part B: Pharmacokinetics (PK): Steady-state Area Under the Concentration Time Curve From Time Zero to the End of the Dosing Interval, Tau (AUC[0-tau]) of LY3502970 on Day 7
研究概览
简要总结
The main purpose of this study is to see how much of orforglipron (study drug) gets into the bloodstream and how long it takes the body to get rid of it when given as capsules compared to tablets in healthy overweight and obese participants. The safety and tolerability (side effects) of orforglipron when given as capsules and tablets will also be evaluated.
The study will be conducted in two parts, with part A and B lasting up to approximately 25 and 22 weeks each respectively, including the screening period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants who are overtly healthy as determined by medical history and physical examination.
- •Have a stable body weight for one month prior to screening (less than or equal to 5 percent body weight gain or loss) and Body Mass Index (BMI) in range of 27 to 40 kilogram per meter square (kg/m²).
- •Participants must be reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
- •Have venous access sufficient to allow for blood sampling.
排除标准
- •Have hemoglobin A1c (HbA1c) level of 6.5 percent (%) or greater.
- •Have a history of current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders or other significant active, uncontrolled medical conditions.
- •Have significant history of or currently have major depressive disorder or psychiatric disorder within the last 2 years.
- •Obesity induced by other endocrine disorders, such as Cushing's syndrome or Prader-Willi syndrome.
- •Have known clinically significant gastric emptying abnormality.
- •Have undergone bariatric surgery (for example: Lap-Band, Gastric Bypass)
- •Have a known self or family history (first-degree relative) of multiple endocrine neoplasia type 2A or type 2B, thyroid C-cell hyperplasia, or any form of thyroid cancer.
- •Have an abnormal 12-lead electrocardiogram (ECG) at screening.
- •Have history of pancreatitis.
- •Judged by the study investigator to be at serious suicidal risk and have answered "Yes" to either question 4 or 5 on the Columbia-Suicide Severity Rating Scale [C-SSRS]).
- •Have difficulty swallowing capsules or tablets.
研究组 & 干预措施
Part B: LY3502970 Oral Administration (Cohort 1B, Sequence 1)
Participants received LY3502970 orally QD across inpatient Treatment Periods 1-9 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows:
- Period 1: 1 mg (Capsule- First Treatment)
- Period 2: 1 mg (Capsule- Second Treatment)
- Period 3: 0.8 mg (Tablet)
- Period 4: 3 mg (Capsule- First Treatment)
- Period 5: 3 mg (Capsule- Second Treatment)
- Period 6: 2.5 mg (Tablet)
- Period 7: 6 mg (Capsule- First Treatment)
- Period 8: 6 mg (Capsule- Second Treatment)
- Period 9: 5.5 mg (Tablet)
干预措施: Orforglipron (Drug)
Part A: LY3502970 Oral Administration (Cohort 1A, Sequence 2)
Participants received LY3502970 orally QD across inpatient Treatment Periods 1-12 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows:
- Period 1: Dose Level 2 (Tablet)
- Period 2: 1 mg (Capsule)
- Period 3: Dose Level 3 (Tablet)
- Period 4: Dose Level 1 (Tablet)
- Period 5: Dose Level 5 (Tablet)
- Period 6: 3 mg (Capsule)
- Period 7: Dose Level 6 (Tablet)
- Period 8: Dose Level 4 (Tablet)
- Period 9: Dose Level 8 (Tablet)
- Period 10: 6 mg (Capsule)
- Period 11: Dose Level 9 (Tablet)
- Period 12: Dose Level 7 (Tablet)
干预措施: Orforglipron (Drug)
Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 3)
Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg and 6 mg; Capsule), followed by inpatient Treatment Periods 7-18 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows:
- Period 7: Dose Level 10 (Tablet)
- Period 8: Dose Level 12 (Tablet)
- Period 9: 12 mg (Capsule)
- Period 10: Dose Level 11 (Tablet)
- Period 11: Dose Level 13 (Tablet)
- Period 12: Dose Level 16 (Tablet)
- Period 13: 24 mg (Capsule)
- Period 14: Dose Level 14 (Tablet)
- Period 15: Dose Level 15 (Tablet)
- Period 16: Dose Level 18 (Tablet)
- Period 17: 36 mg (Capsule)
- Period 18: Dose Level 17 (Tablet)
干预措施: Orforglipron (Drug)
Part B: LY3502970 Oral Administration (Cohort 2B, Sequence 3)
Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg [Capsule]), followed by inpatient Treatment Periods 7-15 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows:
- Period 7: 9 mg (Tablet)
- Period 8: 12 mg (Capsule- First Treatment)
- Period 9: 12 mg (Capsule- Second Treatment)
- Period 10: 14.5 mg (Tablet)
- Period 11: 24 mg (Capsule- First Treatment)
- Period 12: 24 mg (Capsule- Second Treatment)
- Period 13: 17.2 mg (Tablet)
- Period 14: 36 mg (Capsule- First Treatment)
- Period 15: 36 mg (Capsule- Second Treatment)
干预措施: Orforglipron (Drug)
Part A: LY3502970 QD Oral Administration (Cohort 1A, Sequence 1)
Participants received LY3502970 orally once daily (QD) across inpatient Treatment Periods 1-12 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows:
- Period 1: 1 mg (Capsule)
- Period 2: Dose Level 2 (Tablet)
- Period 3: Dose Level 1 (Tablet)
- Period 4: Dose Level 3 (Tablet)
- Period 5: 3 mg (Capsule)
- Period 6: Dose Level 5 (Tablet)
- Period 7: Dose Level 4 (Tablet)
- Period 8: Dose Level 6 (Tablet)
- Period 9: 6 mg (Capsule)
- Period 10: Dose Level 8 (Tablet)
- Period 11: Dose Level 7 (Tablet)
- Period 12: Dose Level 9 (Tablet)
干预措施: Orforglipron (Drug)
Part A: LY3502970 Oral Administration (Cohort 1A, Sequence 4)
Participants received LY3502970 orally QD across inpatient Treatment Periods 1-12 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows:
- Period 1: Dose Level 3 (Tablet)
- Period 2: Dose Level 1 (Tablet)
- Period 3: Dose Level 2 (Tablet)
- Period 4: 1 mg (Capsule)
- Period 5: Dose Level 6 (Tablet)
- Period 6: Dose Level 4 (Tablet)
- Period 7: Dose Level 5 (Tablet)
- Period 8: 3 mg (Capsule)
- Period 9: Dose Level 9 (Tablet)
- Period 10: Dose Level 7 (Tablet)
- Period 11: Dose Level 8 (Tablet)
- Period 12: 6 mg (Capsule)
干预措施: Orforglipron (Drug)
Part B: LY3502970 Oral Administration (Cohort 1B, Sequence 3)
Participants received LY3502970 orally QD across inpatient Treatment Periods 1-9 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows:
- Period 1: 0.8 mg (Tablet)
- Period 2: 1 mg (Capsule- First Treatment)
- Period 3: 1 mg (Capsule- Second Treatment)
- Period 4: 2.5 mg (Tablet)
- Period 5: 3 mg (Capsule- First Treatment)
- Period 6: 3 mg (Capsule- Second Treatment)
- Period 7: 5.5 mg (Tablet)
- Period 8: 6 mg (Capsule- First Treatment)
- Period 9: 6 mg (Capsule- Second Treatment)
干预措施: Orforglipron (Drug)
Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 1)
Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg and 6 mg; Capsule), followed by inpatient Treatment Periods 7-18 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows:
- Period 7: 12 mg (Capsule)
- Period 8: Dose Level 11 (Tablet)
- Period 9: Dose Level 10 (Tablet)
- Period 10: Dose Level 12 (Tablet)
- Period 11: 24 mg (Capsule)
- Period 12: Dose Level 14 (Tablet)
- Period 13: Dose Level 13 (Tablet)
- Period 14: Dose Level 16 (Tablet)
- Period 15: 36 mg (Capsule)
- Period 16: Dose Level 17 (Tablet)
- Period 17: Dose Level 15 (Tablet)
- Period 18: Dose Level 18 (Tablet)
干预措施: Orforglipron (Drug)
Part B: LY3502970 Oral Administration (Cohort 1B, Sequence 2)
Participants received LY3502970 orally QD across inpatient Treatment Periods 1-9 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows:
- Period 1: 1 mg (Capsule- First Treatment)
- Period 2: 0.8 mg (Tablet)
- Period 3: 1 mg (Capsule- Second Treatment)
- Period 4: 3 mg (Capsule- First Treatment)
- Period 5: 2.5 mg (Tablet)
- Period 6: 3 mg (Capsule- Second Treatment)
- Period 7: 6 mg (Capsule- First Treatment)
- Period 8: 5.5 mg (Tablet)
- Period 9: 6 mg (Capsule- Second Treatment)
干预措施: Orforglipron (Drug)
Part A: LY3502970 Oral Administration (Cohort 1A, Sequence 3)
Participants received LY3502970 orally QD across inpatient Treatment Periods 1-12 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows:
- Period 1: Dose Level 1 (Tablet)
- Period 2: Dose Level 3 (Tablet)
- Period 3: 1 mg (Capsule)
- Period 4: Dose Level 2 (Tablet)
- Period 5: Dose Level 4 (Tablet)
- Period 6: Dose Level 6 (Tablet)
- Period 7: 3 mg (Capsule)
- Period 8: Dose Level 5 (Tablet)
- Period 9: Dose Level 7 (Tablet)
- Period 10: Dose Level 9 (Tablet)
- Period 11: 6 mg (Capsule)
- Period 12: Dose Level 8 (Tablet)
干预措施: Orforglipron (Drug)
Part B: LY3502970 Oral Administration (Cohort 2B, Sequence 2)
Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg [Capsule]), followed by inpatient Treatment Periods 7-15 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows:
- Period 7: 12 mg (Capsule- First Treatment)
- Period 8: 9 mg (Tablet)
- Period 9: 12 mg (Capsule- Second Treatment)
- Period 10: 24 mg (Capsule- First Treatment)
- Period 11: 14.5 mg (Tablet)
- Period 12: 24 mg (Capsule- Second Treatment)
- Period 13: 36 mg (Capsule- First Treatment)
- Period 14: 17.2 mg (Tablet)
- Period 15: 36 mg (Capsule- Second Treatment)
干预措施: Orforglipron (Drug)
Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 2)
Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg; Capsule), followed by inpatient Treatment Periods 7-18 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows:
- Period 7: Dose Level 11 (Tablet)
- Period 8: 12 mg (Capsule)
- Period 9: Dose Level 12 (Tablet)
- Period 10: Dose Level 10 (Tablet)
- Period 11: Dose Level 14 (Tablet)
- Period 12: 24 mg (Capsule)
- Period 13: Dose Level 16 (Tablet)
- Period 14: Dose Level 13 (Tablet)
- Period 15: Dose Level 17 (Tablet)
- Period 16: 36 mg (Capsule)
- Period 17: Dose Level 18 (Tablet)
- Period 18: Dose Level 15 (Tablet)
干预措施: Orforglipron (Drug)
Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 4)
Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg; Capsule), followed by inpatient Treatment Periods 7-18 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows:
- Period 7: Dose Level 12 (Tablet)
- Period 8: Dose Level 10 (Tablet)
- Period 9: Dose Level 11 (Tablet)
- Period 10: 12 mg (Capsule)
- Period 11: Dose Level 16 (Tablet)
- Period 12: Dose Level 13 (Tablet)
- Period 13: Dose Level 14 (Tablet)
- Period 14: 24 mg (Capsule)
- Period 15: Dose Level 18 (Tablet)
- Period 16: Dose Level 15 (Tablet)
- Period 17: Dose Level 17 (Tablet)
- Period 18: 36 mg (Capsule)
干预措施: Orforglipron (Drug)
Part B: LY3502970 Oral Administration (Cohort 2B, Sequence 1)
Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg [Capsule]), followed by inpatient Treatment Periods 7-15 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows:
- Period 7: 12 mg (Capsule- First Treatment)
- Period 8: 12 mg (Capsule- Second Treatment)
- Period 9: 9 mg (Tablet)
- Period 10: 24 mg (Capsule- First Treatment)
- Period 11: 24 mg (Capsule- Second Treatment)
- Period 12: 14.5 mg (Tablet)
- Period 13: 36 mg (Capsule- First Treatment)
- Period 14: 36 mg (Capsule- Second Treatment)
- Period 15: 17.2 mg (Tablet)
干预措施: Orforglipron (Drug)
结局指标
主要结局
Part B: Pharmacokinetics (PK): Steady-state Area Under the Concentration Time Curve From Time Zero to the End of the Dosing Interval, Tau (AUC[0-tau]) of LY3502970 on Day 7
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16 and 24 hours post-dose on Day 7 for each dosing treatment period (1 period=7 days)
PK: Area under the concentration versus time curve from time 0 to the end of the once daily dosing interval at steady state AUC\[0-tau\] on Day 7.
Part B: PK: Steady-state Maximum Observed Concentration (Cmax) of LY3502970 on Day 7
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16 and 24 hours post-dose on Day 7 for each dosing treatment period (1 period=7 days)
PK: Maximum concentration of LY3502970 during a once daily dosing interval at steady state on Day 7.
次要结局
未报告次要终点