A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Absolute Bioavailability, Pharmacokinetics, and Pharmacodynamics of AGA2118 in Men and Postmenopausal Women
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- Number of participants with clinically significant changes in total calcium (albumin-adjusted) in Part 1 (SAD).
研究概览
简要总结
The primary objectives of the study are to assess the safety and tolerability of AGA2118 after single subcutaneous or intravenous administration in healthy men and postmenopausal women and to assess the safety and tolerability of AGA2118 after multiple subcutaneous administrations in men and postmenopausal women.
详细描述
This is a Phase I, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Absolute Bioavailability, Pharmacokinetics, and Pharmacodynamics of AGA2118 in Men and Postmenopausal Women.
The study consists of the single ascending dose (SAD) part and the multiple ascending dose (MAD) part. In the SAD part, up to 56 healthy men and postmenopausal women will be sequentially enrolled to receive a single subcutaneous (SC) dose of AGA2118 or a single intravenous (IV) dose of AGA2118 or placebo. In the MAD part, up to 32 healthy men and postmenopausal women will be sequentially enrolled in various dose cohorts to receive multiple SC doses every 4 weeks of AGA2118 or placebo.
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
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy men ≥ 30 and ≤ 65 years of age or postmenopausal women ≥ 45 and ≤ 65 years of age for SAD and MAD;
- •BMI ≥ 18.5 and ≤ 32 kg/m^2 (for SAD and MAD).
- •Generally healthy (as assessed by the investigator).
- •Nonsmokers, or light smokers, defined as ≤ 3 cigarettes/day (or equivalent) (for SAD and MAD).
- •Able and willing to correctly and independently complete all study procedures and able to read, understand, and provide written informed consent after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures (for SAD and MAD).
- •A male who is sterile or agrees to the following during the Treatment Period and for at least 6 months after the final dose of investigational product
- •Refrain from donating fresh unwashed semen
- •Plus, either
- •Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
- •Must agree to use contraception as detailed below
- •Agree to use a male condom plus a female partner to use a highly effective method of contraception with a woman of childbearing potential who is not currently pregnant
- •Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person
排除标准
- •A bone fracture within 6 months (for SAD only).
- •Previous exposure to AGA2118 (for MAD only).
- •Any condition that would affect bone metabolism or has a history of low energy fractures as documented in medical history (for MAD only).
- •Administration of the any medications that known to affect bone metabolism within 6 months of Day 1 unless otherwise specified (for SAD and MAD).
- •Human immunodeficiency virus (HIV) infection (for SAD and MAD).
- •Active chronic hepatitis B (HBV) or hepatitis C (HCV) infection including hepatitis B surface antigen and hepatitis C antigen positive participants with or without abnormal liver enzymes (for SAD and MAD).
- •Evidence of any of the following (for SAD and MAD):
- •creatinine ≥ 1.5 × ULN, or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m^2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at screening
- •current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range
- •known intolerance to calcium supplements
- •malignancy within the last 5 years, etc.
研究组 & 干预措施
AGA2118
In SAD part, various single doses of AGA2118 will be administered to the participants via either SC injection or IV infusion. The starting dose was 0.3 mg/kg, with sequential escalation up to 15 mg/kg.
In MAD part, various multiple doses of AGA2118 will be administered every four weeks (Q4W) to the participants via SC injection for 12 weeks. The starting dose was 1 mg/kg, with sequential escalation up to 12 mg/kg.
干预措施: AGA2118 (Drug)
Placebo
In SAD part, a single dose of placebo comparator will be used for each cohort of either SC or IV administration.
In MAD part, multiple doses of placebo comparator will be used for each cohort of SC administration.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with clinically significant changes in total calcium (albumin-adjusted) in Part 1 (SAD).
时间窗: Up to 85 days
Serum calcium tested at Day 2, 4, 6, 15, 29, 85.
Number of participants with clinically significant changes in blood pressure in Part 1 (SAD).
时间窗: Up to 85 days
Systolic and diastolic blood pressure measured (mmHg) at all clinic visits (Day 1, 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85).
Number of participants with treatment-emergent adverse events (TEAE) in Part 1 (SAD).
时间窗: Up to 85 days
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational product (IP), whether or not considered related to the IP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP.
Number of participants with clinically significant changes in QTcF in Part 1 (SAD).
时间窗: Up to 85 days
QTcF (QT interval corrected for heart rate using Fridericia's formula) measured by electrocardiogram (ECG) on Day 1, 2, 4, 6, 15, 29, 43, 57, 71, 85.
Number of participants with clinically significant changes in heart rate in Part 2 (MAD).
时间窗: Up to day 169
Heart rate measured by electrocardiogram (ECG) on Day 1, 2, 4, 15, 29, 36, 57, 64, 85, 169.
Number of participants with clinically significant changes in total calcium (albumin-adjusted) in Part 2 (MAD).
时间窗: Up to 169 days
Serum calcium tested at Day 2, 8, 15, 29, 36, 57, 64, 85, 169.
Number of participants with clinically significant changes in heart rate in Part 1 (SAD).
时间窗: Up to 85 days
Heart rate measured by electrocardiogram (ECG) on Day 1, 2, 4, 6, 15, 29, 85.
Number of participants with clinically significant changes in QTcF in Part 2 (MAD).
时间窗: Up to day 169
QTcF (QT interval corrected for heart rate using Fridericia's formula) measured by electrocardiogram (ECG) on Day 1, 2, 4, 15, 29, 36, 57, 64, 85, 169.
Number of participants with treatment-emergent adverse events (TEAE) in Part 2 (MAD).
时间窗: Up to 169 days
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational product (IP), whether or not considered related to the IP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP.
Number of participants with clinically significant changes in blood pressure in Part 2 (MAD).
时间窗: Up to 169 days
Systolic and diastolic blood pressure measured (mmHg) at all clinic visits (Day 1, 2, 4, 6, 8, 15, 22, 29, 36, 43, 57, 58, 60, 62, 64, 71, 78, 85, 99, 113, 127, 141, 155, 169).
次要结局
- Area under the concentration time curve (AUC)(Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169)
- Time to maximum concentration (Tmax) of AGA2118(Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169)
- Maximum Concentration (Cmax) of AGA2118(Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169)
- Terminal elimination half-life (t1/2)(Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169)