A Double-Blind, Randomized, Placebo-Controlled, Multiple Ascending 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
- 终止
- 入组人数
- 24
- 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 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
- 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
- •Diagnosis of Type 2 Diabetes Mellitus (T2DM) at least 3 months prior to Screening
- •On a stable treatment regimen at least 3 months prior to Screening of (1) diet and exercise, or (2) metformin monotherapy (at a dose of at least 1,000 milligram (mg) per day)
- •Blood pressure 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 blood pressure is out of range, up to 2 repeated assessments are permitted
- •HbA1c greater than or equal to 6.5% and less than 8.5% at Screening
- •Females of non-childbearing potential
排除标准
- •History of, or currently active, significant illness or medical disorders, including cardiovascular disease (including cardiac arrhythmias, myocardial infarction, stroke, peripheral vascular disease), hematological disease (example, von Willebrand's disease or other bleeding disorders), respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmologic disorders, neoplastic disease, skin disorder, renal disorder, or any other illness that the Principal Investigator (PI) considers should exclude the participant or that could interfere with the interpretation of the study results
- •Previous surgical treatment for obesity (example, gastric bypass, gastric banding)
- •History of diabetic neuropathy with signs of gastroparesis and/or known proliferative retinopathy or maculopathy
- •History or current diagnosis of acute or chronic pancreatitis
- •History of an invasive cardiovascular surgical procedure including, but not limited to, coronary artery bypass graft (CABG), or percutaneous coronary intervention (PCI)
研究组 & 干预措施
Cohort 4 (JNJ-64565111 Repeat or Lower Dose or Placebo)
Participants in ratio of 3:1 will receive a dose of JNJ-64565111 or placebo that would be a repeat or lower dose level previously assessed as well-tolerated.
干预措施: Placebo (Drug)
Cohort 1 (JNJ-64565111 2.5 nmol/kg or Placebo)
Participants in ratio of 3:1 will receive 2.5 Nanomole Per Kilogram (nmol/kg) JNJ-64565111 or placebo.
干预措施: JNJ-64565111 (Drug)
Cohort 1 (JNJ-64565111 2.5 nmol/kg or Placebo)
Participants in ratio of 3:1 will receive 2.5 Nanomole Per Kilogram (nmol/kg) JNJ-64565111 or placebo.
干预措施: Placebo (Drug)
Cohort 2 (JNJ-64565111 3 nmol/kg or Placebo)
Participants in ratio of 3:1 will receive 3.0 nmol/kg JNJ-64565111 or placebo. Dose may be escalated based on review by Sponsor and Principal Investigator of blinded safety, tolerability, pharmacokinetic, and (all available) pharmacodynamic data collected up to Day 29 but dose will not exceed 3.5 nmol/kg.
干预措施: JNJ-64565111 (Drug)
Cohort 2 (JNJ-64565111 3 nmol/kg or Placebo)
Participants in ratio of 3:1 will receive 3.0 nmol/kg JNJ-64565111 or placebo. Dose may be escalated based on review by Sponsor and Principal Investigator of blinded safety, tolerability, pharmacokinetic, and (all available) pharmacodynamic data collected up to Day 29 but dose will not exceed 3.5 nmol/kg.
干预措施: Placebo (Drug)
Cohort 3 (JNJ-64565111 3.5 nmol/kg or Placebo)
Participants in ratio of 3:1 will receive 3.5 nmol/kg JNJ-64565111 or placebo. Dose may be escalated based on review by Sponsor and Principal Investigator of blinded safety, tolerability, pharmacokinetic, and (all available) pharmacodynamic data collected up to Day 29 but dose will not exceed 3.5 nmol/kg.
干预措施: JNJ-64565111 (Drug)
Cohort 3 (JNJ-64565111 3.5 nmol/kg or Placebo)
Participants in ratio of 3:1 will receive 3.5 nmol/kg JNJ-64565111 or placebo. Dose may be escalated based on review by Sponsor and Principal Investigator of blinded safety, tolerability, pharmacokinetic, and (all available) pharmacodynamic data collected up to Day 29 but dose will not exceed 3.5 nmol/kg.
干预措施: Placebo (Drug)
Cohort 4 (JNJ-64565111 Repeat or Lower Dose or Placebo)
Participants in ratio of 3:1 will receive a dose of JNJ-64565111 or placebo that would be a repeat or lower dose level previously assessed as well-tolerated.
干预措施: JNJ-64565111 (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
次要结局
- Change From Baseline in Heart Rate(Baseline, up to Day 72)
- Number of Participants With Incidence of Anti-JNJ-64565111 Antibodies as Measure of Immunogenicity(Up to Day 72)
- Change From Baseline in Body Weight(Baseline, up to Day 72)
- Change From Baseline for 24-hour Mean Plasma Glucose(Baseline, Day 26)
- Change From Baseline in Fasting Plasma Glucose (FPG)(Baseline, up to Day 72)
- Change From Baseline in Hemoglobin A1c (HbA1c)(Baseline, up to Day 72)
- Maximum Observed Plasma Concentration (Cmax)(Up to Day 72)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(Up to Day 72)
- Area Under Concentration from time zero to the last quantifiable concentration AUC(0-last)(Up to Day 72)
- Area Under Curve over the dosing interval AUC(0-tau)(Up to Day 72)
- Elimination Half-Life (t1/2)(Up to Day 72)
- Apparent Clearance (CL/F)(Up to Day 72)
- Apparent Volume of Distribution (V/F)(Up to Day 72)
- Terminal Rate Constant (K)(Up to Day 72)
- Average concentration over the dosing interval at steady state (Caverage,ss)(Up to Day 72)
- Minimum Observed Plasma Concentration (Cmin)(Up to Day 72)
- Area Under Curve from time zero extrapolated to infinity AUC(0-inf)(Up to Day 72)
- Accumulation Ratio(Up to Day 72)
- Change From Baseline in Blood Pressure(Baseline, up to Day 72)
- Change From Baseline on Fasting Lipids(Baseline, up to Day 72)
- Change From Baseline in Insulin Secretion(Baseline, Day 26)
- Change From Baseline in Insulin Sensitivity(Baseline, Day 26)
- Change From Baseline for C-peptide(Baseline, Day 26)
- Change From Baseline for Glucagon(Baseline, Day 26)