Phase II Clinical Study of Single Oral Administration of GS3-007a for Oral Suspension in the Diagnosis of AGHD: A Multicenter, Randomized, Open-Label, Three-Way Crossover Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- ROC curves and the area under the curve (AUC) of the ROC curves
研究概览
简要总结
The GS3-007a Growth Hormone Stimulation Test (GHST) will be compared with the Insulin Tolerance Test (ITT) in an open-label, randomized, three-way crossover trial. The trial will include subjects suspected to have adult growth hormone deficiency (AGHD) and a group of healthy control subjects.
详细描述
Trial subjects will be assigned to groups of descending likelihood of having AGHD:
Group A: High likelihood of AGHD Group B: Intermediate likelihood of AGHD Group C: Low likelihood of AGHD Group D: Healthy control subjects matched to Group A. The sequential of the GHSTs for Group A-C will be determined by randomization. Group D will undergo testing in the same sequence as their matched Group A counterparts Serum growth hormone (GH) concentrations will be measured at predefined time points before and after GHST with GS3-007a or insulin. The peak GH value and diagnostic cut-off for GS3-007a dry suspension will be evaluated using receiver operating characteristic (ROC) curves. Safety, pharmacokinetics (PK), and pharmacodynamics (PD) outcomes were assessed for GS3-007a. The Insulin Tolerance Test (ITT) served as the comparator to determine positive and negative agreement with GS3-007a GHSTs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
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
- 否
入选标准
- •Suspected AGHD Subjects (Groups A, B, and C):
- •Age ≥ 18 years and ≤ 65 years, male or female.
- •Suspected AGHD, meeting at least one of the following criteria:
- •Congenital structural/gene defects in the hypothalamus or pituitary gland, or
- •History of surgery or radiotherapy in the hypothalamic or pituitary region, or
- •Adult traumatic brain injury (TBI) or central nervous system (CNS) infection, or
- •Confirmed deficiency of at least one pituitary hormone other than growth hormone (GH), or
- •Idiopathic childhood-onset GHD.
- •IGF-1 SDS <
- •Willing and able to comply with the study procedures and voluntarily sign the informed consent form.
- •Matched Healthy Control Subjects (Group D):
- •Age ≥ 18 years and ≤ 65 years, male or female.
- •Matching criteria with Group A (subjects with highly suspected AGHD):
- •(If feasible) Estrogen use and administration route (oral, transdermal) in females:
排除标准
- •Known or suspected hypersensitivity to growth hormone secretagogues (GHS) or their excipients or known allergy to insulin or its excipients.
- •Clinically significant conditions newly diagnosed within 6 months before screening, making the subject unsuitable for ITT:
- •Chronic congestive heart failure (New York Heart Association (NYHA) Class III or higher);
- •Other significant cardiovascular/cerebrovascular diseases, e.g., uncontrolled severe hypertension, severe arrhythmia, stroke or transient ischemic attack (TIA), or confirmed coronary artery disease;
- •Traumatic brain injury (TBI).
- •Short-acting GH therapy within 30 days before screening.
- •Long-acting GH therapy within 90 days before screening.
- •GH stimulation test performed within 7 days before the first dose.
- •Abnormal thyroid function during screening, or any adjustment to thyroid hormone replacement therapy dosage prior to the first study dose.
- •Abnormal gonadal function during screening, or any adjustment to testosterone/estrogen replacement therapy dosage prior to the first study dose.
- •Abnormal adrenal function during screening, or any adjustment to glucocorticoid replacement therapy dosage prior to the first study dose.
- •Type 1 diabetes diagnosed before screening, or uncontrolled Type 2 diabetes
- •Body mass index (BMI) ≥40.0 kg/m².
- •Major surgery (e.g., coronary bypass, hepatectomy/nephrectomy, gynecologic surgery) within 6 months before screening.
- •Acute neurological, digestive, respiratory, circulatory, endocrine, or hematologic diseases within 3 months before screening, judged by the investigator to potentially affect drug absorption, distribution, metabolism, excretion (ADME), or safety evaluation.
- •History or current diagnosis of malignancy (any type) before screening.
- •Electrocardiogram (ECG) findings during screening indicating QTc interval >450 ms, or history of corrected QT interval (QTc) prolongation, or other clinically significant ECG abnormalities, or use of medications known to prolong QTc interval.
- •Sellar region MRI scan during screening showing untreated intracranial tumor growth.
- •History of clinically symptomatic psychiatric disorders persisting at screening.
- •History of Parkinson's disease or epilepsy persisting at screening.
- •Females with positive blood human chorionic gonadotropin (hCG) during screening, or lactating females, or females planning pregnancy from screening through follow-up completion.
- •Liver function abnormalities during screening
- •Use of medications directly affecting pituitary GH secretion or somatostatin-releasing drugs within a period >5 half-lives before first study dose.
- •Use of strong cytochrome P450 family 3 subfamily A member 4/5 (CYP3A4/5) inhibitors or inducers.
- •Participation in any other drug or medical device clinical trial within 1 month prior to screening, or screening occurring within 5 half-lives of the investigational drug (whichever is longer).
- •Unwillingness to use protocol-specified contraception methods
- •Other conditions deemed by the investigator to make the subject unsuitable for participation in this clinical trial.
研究组 & 干预措施
GHST Sequence 3
Insulin Tolerance Test, GS3-007a low dose, GS3-007a high dose
干预措施: Insulin (Drug)
GHST Sequence 1
GS3-007a low dose, GS3-007a high dose, Insulin Tolerance Test
干预措施: GS3-007a dry suspension (Drug)
GHST Sequence 2
GS3-007a high dose, Insulin Tolerance Test, GS3-007a low dose
干预措施: GS3-007a dry suspension (Drug)
GHST Sequence 3
Insulin Tolerance Test, GS3-007a low dose, GS3-007a high dose
干预措施: GS3-007a dry suspension (Drug)
GHST Sequence 1
GS3-007a low dose, GS3-007a high dose, Insulin Tolerance Test
干预措施: Insulin (Drug)
GHST Sequence 2
GS3-007a high dose, Insulin Tolerance Test, GS3-007a low dose
干预措施: Insulin (Drug)
结局指标
主要结局
ROC curves and the area under the curve (AUC) of the ROC curves
时间窗: up to 120minutes
次要结局
- Youden index of the ROC curve for GS3-007a dry suspension(up to 120minutes)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Up to 22 days)