Phase 2, Double-Blind Randomized, 3-way Cross-Over Liquid Meal Study With Optimal Doses of SC Administered Insulin Lispro With and Without rHuPH20 and Regular Human Insulin With rHuPH20 to Compare Pharmacokinetics, Postprandial Glycemic Response, and Optimal Insulin Dose in Patients With T2DM
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Postprandial Glucose (PPG) Excursion Following a Liquid Meal
研究概览
简要总结
This is a single-center, Phase 2, randomized, double-blind, 3-way crossover meal study in participants with Type 2 Diabetes Mellitus (T2DM) to determine the optimum dose and compare the pharmacokinetics (PK) and postprandial glycemic response of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), and Humulin-R + rHuPH20 administered subcutaneously.
详细描述
This study design was chosen to assess the differences between pharmacokinetic (PK) and pharmacodynamic (PD) parameters, including postprandial glycemic response, of Humalog + recombinant human hyaluronidase PH20 (rHuPH20), Humalog alone, and Humulin-R + rHuPH20 at optimal doses following a liquid meal.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female of age 18 to 70 years, inclusive
- •Participants with Type 2 diabetes mellitus (T2DM) per World Health Organization criteria treated with basal and/or bolus insulin for ≥12 months.
- •Body mass index (BMI) between 18 to 45 kilograms per square meter (kg/m^2), inclusive
- •Glycosylated hemoglobin A1c (HbA1c) ≤10%
- •Current treatment with insulin ≥60 Units/day (U/d)
- •A participant taking oral hypoglycemic agents must be on a stable dose for >8 weeks with the exception of thiazolidinediones (TZD), which should be >12 weeks.
- •Total body weight >65 kilograms (kg) (143 pounds [lb]) for men and >46 kg (101 lb) for women
- •Vital signs (blood pressure [BP], pulse rate, and body temperature) within normal range or, if out of range, assessed by the Investigator as not clinically significant (NCS)
- •Participants should be in good general health based on medical history and physical examination without medical conditions that might prevent the completion of study drug injections and assessments in this protocol
- •Decision making capacity and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including adequate venous access.
- •Signed and written Internal Review Board-approved informed consent
排除标准
- •Known or suspected allergy to any components of any of the study drugs in this study
- •Previous enrollment in this study
- •A participant who has proliferative retinopathy, proliferative maculopathy, and/or severe neuropathy (in particular, autonomic neuropathy) as judged by the Investigator
- •As judged by the Investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on electrocardiogram [ECG] and New York Heart Association [NYHA] Class III/IV heart disease), hepatic, neurological, renal, genitourinary, or hematological systems
- •As judged by the Investigator, uncontrolled hypertension (diastolic BP ≥100 millimeters of mercury [mmHg] and/or systolic BP ≥160 mmHg after 5 minutes in the supine position).
- •As judged by the Investigator, clinically significant findings in routine laboratory data (anemia with hematocrit less than 33% at screening is specifically exclusionary)
- •Positive human immunodeficiency virus (HIV) antibody test, hepatitis B (anti-HBsAg), or hepatitis C (anti-HCV) antibody test
- •Current addiction to alcohol or substances of abuse as determined by the Investigator
- •Known use of drugs (other than oral hypoglycemic agents) that may interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia
- •Recurrent major hypoglycemia or hypoglycemic unawareness as determined by the Investigator
- •Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study
- •Symptomatic gastroparesis
- •Donation of blood in excess of 500 milliliters (mL) within 56 days before dosing
- •Use of any investigational drug or device 30 days before enrollment in this study
- •Pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, intra-uterine device [IUD], oral or injectable contraceptives, barrier methods, or remaining abstinent)
- •Any condition (intrinsic or extrinsic) that, in the judgment of the Investigator, will interfere with study participation or evaluation of data
研究组 & 干预措施
Humalog, Then Humalog + rHuPH20, Then Humulin-R + rHuPH20
A subcutaneous (SC) injection of 0.3- to 0.5-units per kilogram (U/kg) of Humalog alone for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout period), followed by a SC injection of the appropriate dose of Humalog. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog + 3.75 nanograms/kilogram (ng/kg) recombinant human hyaluronidase PH20 (rHuPH20). The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 ng/kg rHuPH20 following a 3 to 14 day washout period.
干预措施: Humalog (Drug)
Humalog, Then Humalog + rHuPH20, Then Humulin-R + rHuPH20
A subcutaneous (SC) injection of 0.3- to 0.5-units per kilogram (U/kg) of Humalog alone for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout period), followed by a SC injection of the appropriate dose of Humalog. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog + 3.75 nanograms/kilogram (ng/kg) recombinant human hyaluronidase PH20 (rHuPH20). The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 ng/kg rHuPH20 following a 3 to 14 day washout period.
干预措施: Humulin-R (Drug)
Humalog, Then Humalog + rHuPH20, Then Humulin-R + rHuPH20
A subcutaneous (SC) injection of 0.3- to 0.5-units per kilogram (U/kg) of Humalog alone for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout period), followed by a SC injection of the appropriate dose of Humalog. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog + 3.75 nanograms/kilogram (ng/kg) recombinant human hyaluronidase PH20 (rHuPH20). The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 ng/kg rHuPH20 following a 3 to 14 day washout period.
干预措施: Recombinant human hyaluronidase PH20 (rHuPH20) (Drug)
Humalog, Then Humulin-R + rHuPH20, Then Humalog + rHuPH20
A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog alone for up to 3 dose finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 nanograms/kilogram (ng/kg) recombinant human hyaluronidase PH20 (rHuPH20). The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period.
干预措施: Humalog (Drug)
Humalog, Then Humulin-R + rHuPH20, Then Humalog + rHuPH20
A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog alone for up to 3 dose finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 nanograms/kilogram (ng/kg) recombinant human hyaluronidase PH20 (rHuPH20). The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period.
干预措施: Humulin-R (Drug)
Humalog, Then Humulin-R + rHuPH20, Then Humalog + rHuPH20
A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog alone for up to 3 dose finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 nanograms/kilogram (ng/kg) recombinant human hyaluronidase PH20 (rHuPH20). The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period.
干预措施: Recombinant human hyaluronidase PH20 (rHuPH20) (Drug)
Humalog + rHuPH20, Then Humalog, Then Humulin-R + rHuPH20
A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog + 3.75 nanograms per kilogram (ng/kg) recombinant human hyaluronidase PH20(rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog alone. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period.
干预措施: Humalog (Drug)
Humalog + rHuPH20, Then Humalog, Then Humulin-R + rHuPH20
A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog + 3.75 nanograms per kilogram (ng/kg) recombinant human hyaluronidase PH20(rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog alone. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period.
干预措施: Humulin-R (Drug)
Humalog + rHuPH20, Then Humalog, Then Humulin-R + rHuPH20
A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog + 3.75 nanograms per kilogram (ng/kg) recombinant human hyaluronidase PH20(rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog alone. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period.
干预措施: Recombinant human hyaluronidase PH20 (rHuPH20) (Drug)
Humalog + rHuPH20, Then Humulin-R + rHuPH20, Then Humalog
A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humulin-R + rHuPH20. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog following a 3- to 14-day washout period.
干预措施: Humalog (Drug)
Humalog + rHuPH20, Then Humulin-R + rHuPH20, Then Humalog
A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humulin-R + rHuPH20. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog following a 3- to 14-day washout period.
干预措施: Humulin-R (Drug)
Humalog + rHuPH20, Then Humulin-R + rHuPH20, Then Humalog
A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humulin-R + rHuPH20. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog following a 3- to 14-day washout period.
干预措施: Recombinant human hyaluronidase PH20 (rHuPH20) (Drug)
Humulin-R + rHuPH20, Then Humalog, Then Humalog + rHuPH20
A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humulin-R + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humulin-R + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog alone. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period.
干预措施: Humalog (Drug)
Humulin-R + rHuPH20, Then Humalog, Then Humalog + rHuPH20
A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humulin-R + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humulin-R + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog alone. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period.
干预措施: Humulin-R (Drug)
Humulin-R + rHuPH20, Then Humalog, Then Humalog + rHuPH20
A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humulin-R + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humulin-R + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog alone. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period.
干预措施: Recombinant human hyaluronidase PH20 (rHuPH20) (Drug)
Humulin-R + rHuPH20, Then Humalog + rHuPH20, Then Humalog
A subcutaneous (SC) injection of 0.3- to 0.5-units per kilogram (U/kg) of Humulin-R + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humulin-R + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog alone following a 3- to 14-day washout period.
干预措施: Humalog (Drug)
Humulin-R + rHuPH20, Then Humalog + rHuPH20, Then Humalog
A subcutaneous (SC) injection of 0.3- to 0.5-units per kilogram (U/kg) of Humulin-R + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humulin-R + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog alone following a 3- to 14-day washout period.
干预措施: Humulin-R (Drug)
Humulin-R + rHuPH20, Then Humalog + rHuPH20, Then Humalog
A subcutaneous (SC) injection of 0.3- to 0.5-units per kilogram (U/kg) of Humulin-R + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humulin-R + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog alone following a 3- to 14-day washout period.
干预措施: Recombinant human hyaluronidase PH20 (rHuPH20) (Drug)
结局指标
主要结局
Postprandial Glucose (PPG) Excursion Following a Liquid Meal
时间窗: Predose up to 480 minutes after study drug injection
Postprandial glucose (PPG) values in participants receiving Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 following a liquid meal are reported. Blood samples were collected at 30, 20, 10, and within 5 minutes before and at 3, 6, 9, 12, 15, 20, 25, 30, 45, 60, 75, 90, 120, 150, 180, 210, 240, 300, 360, 420, and 480 minutes after injection of each study drug. Least square mean difference was calculated and tested using repeated measures analysis of variance with fixed effect for treatment.
次要结局
- Maximum Serum Insulin Concentration (Cmax)(Predose up to 480 minutes after study drug injection)
- Time To Maximum Serum Insulin Concentration (Tmax)(Predose up to 480 minutes after study drug injection)
- Time to Early 50% Maximum Serum Insulin Concentration (Early[t50%])(Predose up to 120 minutes after study drug injection)
- Time to Late 50% Maximum Serum Insulin Concentration (Late[t50%])(Predose up to 480 minutes after study drug injection)
- Mean Residence Time From Time 0 to the End of Blood Sampling (MRT[Last])(Predose up to 480 minutes after study drug injection)
- Area Under the Concentration Time-Curve for Serum Insulin From Time 0 to the End of Blood Sampling (AUC[Last])(Predose up to 480 minutes after study drug injection)
- Area Under the Time-Concentration Curve for Blood Glucose (AUC[BG])(Predose up to 480 minutes after study drug injection)
- Minimum Postprandial Glucose (PPG)(Predose up to 480 minutes after study drug injection)
- Percentage of Participants Without Hypoglycemia(Predose up to 480 minutes after study drug injection)
- Time to Percentage of Insulin Exposure (as Measured by Area Under the Curve [AUC])(Predose up to 480 minutes following after injection of study drug)