A Randomized, Double-blind, Placebo-controlled, First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Food-effect of ACCG-2671
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 164
- 试验地点
- 8
- 主要终点
- Number of participants with one or more adverse events (AEs) as assessed by CTCAE v5.0
研究概览
简要总结
This first-in-human study will evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of ACCG-2671. It will also evaluate the effect of food on the pharmacokinetics, safety, and tolerability of a single dose. Parts 1 and 2 will enroll healthy participants, and Part 3 will enroll otherwise healthy participants with obesity.
详细描述
ACCG-2671 is a nonpeptide dual amylin and calcitonin receptor agonist (DACRA)
This study comprises 3 parts:
Part 1 (Single Ascending Dose [SAD]) will be conducted in healthy participants to assess the safety, tolerability, and PK profile of a single oral dose of ACCG-2671 or -matched placebo (SAD Cohorts 1 through 5).
Part 2 (Food Effect) will be conducted in healthy participants to assess the effect of food intake on the PK, safety, and tolerability of a single oral dose of ACCG-2671 under fasted and fed conditions.
Part 3 (Multiple Ascending Dose [MAD]) will be conducted in otherwise healthy, participants with obesity (BMI ≥ 30 kg/m2) to assess the safety, tolerability, PK profiles of ACCG-2671 or matched placebo administered for 84 days (MAD Cohorts 1 through 5)
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
- 25 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent
- •Men and women with the following at the time of Screening for Part 1 and 2: ≥25 years and ≤65 years of age and BMI ≥18.0 kg/m2 and <30.0 kg/m2
- •For Part 3, ≥25 years and ≤75 years of age and BMI ≥30.0 kg/m2
- •For Part 3, receiving a stable dose of an injectable GLP-1RA for ≥3 months, who responded to GLP1RA treatment with stable body weight and no ongoing GLP-1RA-related symptoms or AEs. For the duration of the study, participants must not be planning to change GLP-1RA dose or discontinue GLP-1RA treatment
- •Body weight ≥50.0 kg at time of screening
排除标准
- •For Parts 1 and Part 2: Participants with any clinically significant medical conditions are excluded from the study.
- •For Parts 1, 2 and 3: participants will be excluded from this study if there is evidence of ANY of the exclusion criteria at the Screening Visit or prior to first dose administration
- •History or presence of significant CV, pulmonary, hepatic, renal, hematological, GI, endocrine, immunologic, dermatologic, psychiatric, or neurological disease, including any acute illness or major surgery within the past 3 months, or any clinical laboratory abnormality determined by the Investigator to be clinically significant
- •Use of any prescription or over-the counter-medication including herbal products, diet aids, vitamins, or hormone supplements (including contraceptives) within 10 days or 5 times the apparent elimination half-life of the medication (whichever is longer) before the first study drug administration and throughout the study. Exceptions include injectable GLP-1RA treatment for Part 3, Cohort 2c only and medications used to manage AEs at the discretion of an investigator after consultation with the Sponsor.
研究组 & 干预措施
Placebo Part 1 (SAD)
Administered orally in healthy participants
干预措施: Placebo (Drug)
ACCG-2671 Part 3 (MAD)
Escalating doses of ACCG-2671 administered orally for 84 days in participants living with obesity (BMI≥30 kg/m2)
干预措施: ACCG-2671 (Drug)
Placebo Part 3 (MAD)
Placebo administered orally for 84 days in participants living with obesity (BMI≥30 kg/m2)
干预措施: Placebo (Drug)
Part 1 (SAD)
Ascending doses of ACCG-2671 administered orally in healthy participants
干预措施: ACCG-2671 (Drug)
Part 2 (Food-effect)
Single low dose of ACCG-2671 administered orally in healthy participants under fasted and fed state
干预措施: ACCG-2671 (Drug)
结局指标
主要结局
Number of participants with one or more adverse events (AEs) as assessed by CTCAE v5.0
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 24 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Number of participants with one or more serious adverse advents (SAEs) as assessed by CTCAE v5.0
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 24 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Number of participants with one or more treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0
时间窗: Baseline to Day 21 (Part 2)
Change from baseline in systolic blood pressure
时间窗: Baseline to Day 15 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in diastolic blood pressure
时间窗: Baseline to Day 15 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in heart rate
时间窗: Baseline to Day 15 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in ECG ventricular heart rate
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); predose to Day 70 (Part 3)
Change from baseline in ECG PR interval
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); predose to Day 70 (Part 3)
Change from baseline ECG QRS duration
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); predose to Day 70 (Part 3)
Change from baseline in ECG QT Interval corrected using Fridericia's Formula (QTcF)
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); predose to Day 70 (Part 3)
Change from baseline in hemoglobin
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in hematocrit
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in thrombocyte count (platelet count)
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in white blood cell (WBC) count
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in prothrombin time
时间窗: Baseline to day 17 (Part 1, Cohorts 1, 2, and 3); baseline to day 22 (Part 1, Cohorts 4 and 5); baseline to day 21 (Part 2); baseline to day 112 (Part 3)
Change from baseline in international normalized ratio (INR)
时间窗: Baseline to day 17 (Part 1, Cohorts 1, 2 and 3); baseline to day 22 (Part 1 Cohorts 4 and 5); baseline to day 21 (Part 2); baseline to day 112 (Part 3)
Change from baseline in activated partial thromboplastin time (aPTT)
时间窗: Baseline to day 17 (Part 1, Cohorts 1, 2 and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in fibrinogen activity
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2 and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in sodium
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in potassium
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in chloride
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in phosphate
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in calcium
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in glucose
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in amylase
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in lipase
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in magnesium
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in albumin
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in lactate dehydrogenase (LDH)
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in creatine kinase
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in creatinine
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in blood urea nitrogen
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in alanine aminotransferase (ALT)
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in total alkaline phosphatase
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in aspartate aminotransferase (AST)
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in gamma-glutamyl transferase (GGT)
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in total bilirubin
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in direct bilirubin
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in indirect bilirubin
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Number of participants with abnormal urinalysis parameters
时间窗: Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3)
Change from baseline in urinalysis (Including pH, specific gravity, glucose, protein, ketones, blood, nitrites, urobilinogen, and leukocyte esterase)
次要结局
- Maximum observed plasma concentration (Cmax) of ACCG-2671(Predose through Day 22 (Part 1); predose through Day 18 (Part 2); predose through Day 112 (Part 3))
- Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of ACCG-2671(Predose through Day 22 (Part 1); predose through Day 18 (Part 2))
- Area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t) of ACCG-2671(Predose through Day 22 (Part 1); predose through Day 18 (Part 2); predose through Day 112 (Part 3))
- Area under the plasma concentration-time curve over a dosing interval (AUC0-tau) of ACCG-2671(Predose through Day 112 (Part 3))
- Time to reach maximum observed plasma concentration (Tmax) of ACCG-2671(Predose through Day 22 (Part 1); predose through Day 18 (Part 2); predose through Day 112 (Part 3))
- Terminal elimination half-life (t½) of ACCG-2671(Predose through Day 22 (Part 1); predose through Day 18 (Part 2); predose through Day 112 (Part 3))
- Trough plasma concentration (Ctrough) of ACCG-2671(Predose through Day 112 (Part 3))
- Amount of ACCG-2671 excreted unchanged in urine (Ae)(Day -1 through Day 7 (Part 1, Cohorts 4 and 5))
- Fraction of ACCG-2671 excreted unchanged in urine (Fe)(Day -1 through Day 7 (Part 1, Cohorts 4 and 5))
- Renal clearance (CLr) of ACCG-2671(Day -1 through Day 7 (Part 1, Cohorts 4 and 5))