A Double-Blind, Randomized, Placebo-Controlled, Multiple Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-64565111 in Men and Women With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 2
- 主要终点
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability
研究概览
简要总结
The purpose of this Phase 1b study is to assess the safety and tolerability of JNJ-64565111 in adult men and women (of non-child bearing potential) with Type 2 Diabetes Mellitus.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, 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
- •Diagnosis of type 2 diabetes mellitus (T2DM) at least 3 months prior to Screening
- •Hemoglobin A1c (HbA1c) greater than or equal to (>=) 7.0 percent (%) and lesser than or equal to (<=)9.5% at Screening
- •On a stable treatment regimen for at least 3 months prior to Screening of (1) diet and exercise, and/or (2) metformin monotherapy (at a dose of at least 1,000 milligram (mg) per day)
- •Body mass index (BMI) ranging from 25 to 40 kilogram per square meter (kg/m^2) (inclusive), weighing between 75 and 130 kg (inclusive)
- •A woman must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta- hCG) at Screening and Day -2
- •Blood pressure (measured after the participant is sitting/ resting quietly for 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and between 60 and 100 mmHg diastolic, inclusive at Screening (sitting) and Day -2 (supine). If the average of the first triplicate blood pressure assessment is out of range, up to 2 repeated triplicate assessments are permitted
排除标准
- •History or current diagnosis of acute or chronic pancreatitis
- •Familial or personal history of multiple endocrine neoplasia type 2,familial/non-familial medullary thyroid carcinoma
- •Donated blood or blood products or lost a significant amount of blood (>500 milliliter [mL]) within 3 months before the first administration of study drug
- •History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening
- •History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening
研究组 & 干预措施
Cohort 1 to 4: JNJ-64565111 or Placebo
Participants in cohort 1 to 4 in a ratio of 4:1 will receive a dose of JNJ-64565111 or placebo subcutaneously on Days 1, 8, 15 and 22. Cohort 1, 2 and 3 will be dosed in parallel. Dosing for subsequent cohort 4 will be escalated based on review by the Sponsor and Principal Investigator of blinded safety, tolerability, pharmacokinetic, and (all available) pharmacodynamic data collected up to Day 29, but will not exceed from well-tolerated dose.
干预措施: JNJ-64565111 (Drug)
Cohort 1 to 4: JNJ-64565111 or Placebo
Participants in cohort 1 to 4 in a ratio of 4:1 will receive a dose of JNJ-64565111 or placebo subcutaneously on Days 1, 8, 15 and 22. Cohort 1, 2 and 3 will be dosed in parallel. Dosing for subsequent cohort 4 will be escalated based on review by the Sponsor and Principal Investigator of blinded safety, tolerability, pharmacokinetic, and (all available) pharmacodynamic data collected up to Day 29, but will not exceed from well-tolerated dose.
干预措施: Placebo (Drug)
Cohort 5: JNJ-64565111 (Repeat or Lower Dose) or Placebo
Participants in ratio of 4:1 will receive a dose of JNJ-64565111 or placebo subcutaneously on Days 1, 8, 15 and 22, and may be modified. The dose can be repeated or lower than a dose previously assessed as well tolerated.
干预措施: JNJ-64565111 (Drug)
Cohort 5: JNJ-64565111 (Repeat or Lower Dose) or Placebo
Participants in ratio of 4:1 will receive a dose of JNJ-64565111 or placebo subcutaneously on Days 1, 8, 15 and 22, and may be modified. The dose can be repeated or lower than a dose previously assessed as well tolerated.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
时间窗: Up to Day 72
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
次要结局
- Maximum Observed Serum Concentration (Cmax)(First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD.)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD)
- Area Under Concentration-Time Curve From Time Zero to the Last Quantifiable Time (AUC [0-last])(First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD))
- Average Concentration Over the Dosing Interval Tau (T) at Steady State (Caverage,ss)(Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD)
- Minimum Observed Serum Concentration (Cmin)(Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD)
- Accumulation Ratio(First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168 hours PD)
- Area Under Curve over the dosing interval AUC (0-T)(Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168 hours PD)
- Apparent Terminal Elimination Half-life (t1/2term)(Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD)
- Apparent Clearance (CL/F)(Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD)
- Apparent Volume of Distribution (V/F)(Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD)
- Terminal Rate Constant (Kel)(Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD)
- Change From Baseline in Fasting Plasma Glucose (FPG)(Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72)
- Change From Baseline in Hemoglobin A1c (HbA1c)(Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72)
- Number of Participants With Anti-JNJ-64565111 Antibodies as Measure of Immunogenicity(First Dose: Predose (Day 1); Second Dose: predose (Day 8) Third Dose: predose (Day 15); Fourth Dose: predose (Day 22), 144, 480, 720, and 1200 hours post-dose.)
- Change From Baseline in Body Weight(Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72)
- Change From Baseline in Fasting Lipids(Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72)
- Change From Baseline for 24-hour Mean Plasma Glucose(Baseline, Day 26)
- Change From Baseline in C-peptide Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)(Baseline, Day 26)
- Change From Baseline in Total and/or Incremental Plasma Glucose Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)(Baseline, Day 26)
- Change From Baseline in Insulin Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)(Baseline, Day 26)
- Change From Baseline in Glucagon Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)(Baseline, Day 26)
- Change From Baseline in 24-hour Blood Pressure(Baseline and Day 28)
- Change From Baseline in 24-hour Heart Rate(Baseline and Day 28)
- Change From Baseline in Body Mass Index (BMI)(Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72)
- Change From Baseline in Insulin Sensitivity as Assessed by Homeostasis Model Assessment for Insulin Sensitivity (HOMA-%S)(Baseline, Day 26)
- Change From Baseline Insulin Secretion as Assessed by the Insulinogenic Index(Baseline, Day 26)
- Change from Baseline in Insulin Secretion as Assessed by Homeostasis Model Assessment of Beta Cell Function (HOMA-%B)(Baseline, Day 26)
- Change From Baseline in Insulin Sensitivity as Assessed by Matsuda Index(Baseline, Day 26)