A Phase I , Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ISIS 388626 Administered to Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 103
- 试验地点
- 1
- 主要终点
- To evaluate the safety and tolerability of single and multiple doses of ISIS-SGLT2Rx administered subcutaneously
研究概览
简要总结
The primary purpose of this trial is to assess the safety and tolerability of ISIS-SGLT2Rx when given at increasing single doses and to assess the safety and tolerability of the same doses when given multiple times.
详细描述
To evaluate the safety and tolerability of a single subcutaneous injection of ISIS-SGLT2Rx administered at four increasing dose levels (50, 100, 200, 400 mg) and to evaluate the safety and tolerability of multiple doses of ISIS 388626 administered subcutaneously of either 6 or 13 weeks.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age 18 to 65 years
- •Male or female gender although females must be post-menopausal or surgically sterile (hysterectomy, oophorectomy or tubal ligation)
- •Give written informed consent to participate in the study and availability for all study requirements
- •Fasting plasma glucose </= the upper limit of the laboratory's reference range (ULN)
- •HbA1c </= ULN
- •BMI < 30 kg/m²
- •Agree to maintain steady hydration throughout study participation and agree not to fluid restrict
排除标准
- •Pregnant women, nursing mothers or women of childbearing potential
- •Clinically significant abnormalities in medical history or physical examination
- •Clinically significant abnormalities in laboratory examination (including ALT > ULN, AST > ULN, bilirubin > ULN, creatinine > ULN, urine protein positive by urine dipstick, platelets < lower limit of normal and any other clinically significant laboratory findings)
- •Estimated GFR < 60 mL/min per 1.73m²
- •History of clinically significant abnormalities in coagulation parameters
- •Positive test result for HIV, hepatitis B virus, and/or hepatitis C virus
- •Active infection requiring antiviral or antimicrobial therapy
- •Subjects on chronic or acute prescription medication may be permitted after discussion with the Isis Medical Monitor
- •Malignancy (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for > 1 year)
- •Any other concurrent condition which, in the opinion of the Investigator, would preclude participation in this study or interfere with compliance
- •Past and present history of alcohol or drug abuse (defined as > 3 units daily)
- •Undergoing or have undergone treatment with another investigational drug, biologic agent or device within 90 days prior to Screening
- •Blood donation within three months of Screening
研究组 & 干预措施
D
400 mg ISIS 388626 vs Placebo, s.c. injection
干预措施: ISIS 388626 (Drug)
A
50 mg ISIS 388626 vs Placebo, s.c. injection
干预措施: ISIS 388626 (Drug)
B
100 mg ISIS 388626 vs Placebo, s.c. injection
干预措施: ISIS 388626 (Drug)
C
200 mg ISIS 388626 vs Placebo, s.c. injection
干预措施: ISIS 388626 (Drug)
AA
50 mg ISIS 388626, 3x over 1 week s.c. injection, weekly s.c. injection for 5 weeks vs Placebo
干预措施: ISIS 388626 (Drug)
BB
100 mg ISIS 388626, 3x over 1 week s.c. injection, weekly s.c. injection for 5 weeks vs Placebo
干预措施: ISIS 388626 (Drug)
AAA
50 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo
干预措施: ISIS 388626 (Drug)
BBB
100 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo
干预措施: ISIS 388626 (Drug)
CCC
200 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo
干预措施: ISIS 388626 (Drug)
FFF
50 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo
干预措施: ISIS 388626 (Drug)
结局指标
主要结局
To evaluate the safety and tolerability of single and multiple doses of ISIS-SGLT2Rx administered subcutaneously
时间窗: 30 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week dosing
次要结局
- Pharmacokinetic profile all doses and Pharmacodynamics for multi-dose groups(3 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week dosing)