A Phase 1, Randomized, Double-blind, Placebo-controlled, Safety, Tolerability and Pharmacokinetic Study of Escalating Single and Multiple Doses of DGX-001 in Healthy Volunteers Followed by a Stress Exposure Resilience Panel
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 68
- 试验地点
- 1
- 主要终点
- Number of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is a phase 1, randomized, double-blind, placebo-controlled, SAD and MAD study in healthy adult volunteers. DGX-001 is a peptide being investigated for the treatment of the major depressive disorder. This study will examine the safety and tolerability of increasing doses of DGX-001 and, in an exploratory way, potential moderators and functional markers of its activity.
详细描述
The study will be conducted in three parts, Part 1 consisting of SAD cohorts and Part 2 consisting of MAD cohorts and Part 3 consisting of one cohorts of stress exposure resilience panel. In Part 1, approximately 32 adult healthy volunteers will be enrolled sequentially into 1 of 4 single-dose cohorts and will be randomized to receive either a dose of DGX-001 or a placebo. In Part 2, approximately 24 adult healthy volunteers will be enrolled into 1 of 3 multiple-dose cohorts. An adaptive dose-escalation schedule will be employed for both the SAD and MAD parts of the study. In Part 3, 14 subjects will be enrolled in 1 cohorts to further explore the pharmacodynamic effect of DGX-001 under a physiological challenge.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double-blind
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
- •Male or female healthy adult volunteers between 18 to 65 years of age (Both inclusive).
- •The subject's BMI is between 18 and 32 kg/m
- •Female subjects with childbearing potential must have a negative serum pregnancy test.
- •The subject is medically healthy with no clinically significant or relevant abnormalities in medical history, physical exam, vital signs, electrocardiogram (ECG), and laboratory evaluations (hematology, chemistry, and urinalysis) as assessed by the Investigator.
排除标准
- •The subject has a current or recurrent disease that could affect the action, absorption or disposition of the investigational medicinal product or could affect clinical or laboratory assessments.
- •The subject has abnormal renal function test ( <60mL/min, i.e., GFR by Cockroft/Gault) at screening or baseline.
- •The subject has evidence of Gilbert's Syndrome or abnormal liver function test (LFTs >1.5x ULN) at screening or baseline.
- •The subject has had a cholecystectomy or a history of cholecystitis.
- •The subject has clinically significant 12-lead ECG abnormalities, including QTc of 450ms for males and 470ms for females (average of triplicate measures) for any pre-randomization ECG assessment.
- •The subject has a current or relevant history of physical or psychiatric illness.
- •The subject has a documented history of HIV antibody or tested positive for hepatitis B surface antigen (HBsAg) or Hepatitis C virus (HCV) antibody at screening.
- •The subject received an investigational agent within the last 30 days prior to Screening or five half-lives (if known) prior to Screening.
- •The subject has a history of alcohol or other substance abuse within the 12 months prior to dosing.
- •The subject is currently using any medication (including over-the-counter [OTC], herbal or homeopathic preparations), except for hormonal replacement therapy or hormonal contraceptives, that in the opinion of the investigator can not be discontinued and avoided for four weeks before the first dose throughout the study period.
研究组 & 干预措施
Single Ascending Dose Cohort S1
Subjects will receive a single dose of either dose level 1 of DGX-001 or placebo
干预措施: DGX-001Dose 1 (Drug)
Single Ascending Dose Cohort S2
Subjects will receive a single dose of either dose level 2 of DGX-001 or placebo
干预措施: DGX-001 Dose 2 (Drug)
Single Ascending Dose Cohort S3
Subjects will receive a single dose of either dose level 3 of DGX-001 or placebo
干预措施: DGX-001 Dose 3 (Drug)
Single Ascending Dose Cohort S4
Subjects will receive a single dose of either dose level 4 of DGX-001 or placebo
干预措施: DGX-001 Dose 4 (Drug)
Multiple Ascending Doses Cohort M1
Subjects will receive multiple doses of either dose level 1 of DGX-001 or placebo
干预措施: DGX-001Dose 1 (Drug)
Multiple Ascending Doses Cohort M2
Subjects will receive multiple doses of either dose level 2 of DGX-001 or placebo
干预措施: DGX-001 Dose 2 (Drug)
Multiple Ascending Doses Cohort M3
Subjects will receive multiple doses of either dose level 3 of DGX-001 or placebo
干预措施: DGX-001 Dose 3 (Drug)
Stress Exposure Resilience Panel Cohort 1
Subjects will receive any of the MAD dose panel or placebo
干预措施: MAD dose panel of DGX-001 (Drug)
结局指标
主要结局
Number of treatment-emergent adverse events (TEAEs)
时间窗: Day1- Day14
A TEAE is any event that is not present before the initiation of the investigational product or any event already present that worsens in either intensity or frequency following exposure to the investigational product.
Severity of treatment-emergent adverse events as assessed by CTCAE v5.0
时间窗: Day 1- Day14
A TEAE is any event that is not present before the initiation of the investigational product or any event already present that worsens in either intensity or frequency following exposure to the investigational product.
Number of subjects with abnormal and clinically significant safety laboratory tests
时间窗: Day 1- Day 14
Safety laboratory tests include clinical chemistry and hematology
Number of subjects with abnormal and clinically significant electrocardiogram test
时间窗: Day 1- Day 21
12 lead ECGs will be collected in triplicate, which will measure heart rate, PR, QRS, QT, QTc
Number of subjects with abnormal and clinically significant urinalysis findings
时间窗: Day 1-Day 21
This will include routine urine test
次要结局
- CL/F in SAD and MAD(Day 1-Day 9)
- AUCt in SAD and MAD(Day 1-Day 9)
- AUC24 in SAD and MAD(Day 1-Day 9)
- Cmax in SAD and MAD(Day 1-day 9)
- tmax in SAD and MAD(Day 1-Day 9)
- AUC∞ in SAD and MAD(Day 1-Day 9)
- t1/2 in SAD and MAD(Day 1-Day 9)
- Vz/F in SAD and MAD(Day 1-Day 9)
- λz in SAD and MAD(Day 1-Day 9)