A Phase 1, Multiple Ascending Dose Study to Evaluate HMS1005 in Participants With Type 2 Diabetes

Официальное название

A Phase 1, Randomized, Placebo-Controlled, Double-Blind, Multiple- Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HMS1005 in Participants With Type 2 Diabetes

Обзор

The study is to assess the safety, pharmacokinetics, and pharmacodynamic profile of HMS1005 in patient with diabetes

Вмешательства

• Препарат HMS1005
  The investigational medicinal products (IMPs) HMS1005 ER tablets
• Препарат Matching placebo
  Matching placebo

Первичные конечные точки

• Incidence of adverse events [Срок оценки: From enrollment to the end of treatment at Day 19]
• Area under the plasma concentration versus time curve (AUC) [Срок оценки: Single-dose: Day 1-3 steady-state: Day 14-17]
• Maximum observed concentration (Cmax) [Срок оценки: Single-dose: Day 1-3 steady-state: Day 14-17]
• Time of the maximum observed concentration (Tmax) [Срок оценки: Single-dose: Day 1-3 steady-state: Day 14-17]
• Apparent terminal elimination half life (t1/2) [Срок оценки: Single-dose: Day 1-3 steady-state: Day 14-17]

Вторичные конечные точки (2)

• Glucose concentration [Срок оценки: Day -1 and 14]
• Glucose time in range (70-180 mg/dL) % [Срок оценки: From Day -10 (baseline) to Day 17]

Критерии участия

Критерии включения

• Males or females, of any race, between 18 and 65 years of age, inclusive.
• Body mass index between 18 and 38.0 kg/m2, inclusive.
• Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as detailed in Appendix 3.
• T2DM, as determined by the ADA Standard Care Diagnostic Criteria 2025, and

• are drug naïve, treated with diet and exercise, or
• have been on a stable dose of ≤2000 mg metformin for ≥1 month, and/or
• have been on a stable dose of other antidiabetic medications for ≥90 days.
• Except for findings consistent with T2DM, in good health, determined from medical history, 12-lead electrocardiogram (ECG), vital signs measurements, clinical laboratory evaluations, and physical examinations at screening and/or check in, as assessed by the Investigator (or designee).
• Doses of antihypertensive and lipid-lowering therapies must be stable for 30 days prior to screening and remain unchanged during the study unless necessary to protect participant safety on an emergency basis (e.g., hypertensive crisis).
• Glycated hemoglobin between 7.0% and 10.5%, inclusive.
• Fasting plasma glucose between 126 and 240 mg/dL, inclusive. Testing may be repeated once, at the discretion of the Investigator (or designee).
• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.

Критерии исключения

• Type 1 diabetes mellitus, maturity onset diabetes of the young, or diabetes mellitus caused by damage to the pancreas or any other condition (eg, acromegaly or Cushing's syndrome).
• Diabetic neuropathy, retinopathy, or nephropathy.
• History of acute diabetic complications such as diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, lactic acidosis, or hyperosmolar nonketotic coma within the 6 months prior to screening, or chronic metabolic acidosis.
• History of severe hypoglycemia, defined as severe cognitive impairment requiring external assistance for recovery within 3 months prior to dosing; or recurrent hypoglycemia (Level 2), defined as ≥2 episodes within 3 months prior to dosing; or ADA Level 3 hypoglycemia within 6 months prior to dosing.
• Hypoglycemia unawareness or asymptomatic hypoglycemia.
• Clinically significant history of liver disease (eg, hepatitis and cirrhosis) within 1 year prior to screening.
• Clinically significant history of renal disease. Mild to moderate chronic kidney disease is permitted.
• Clinically significant history of cardiovascular disease, particularly coronary artery disease, arrhythmias, atrial tachycardia, or congestive heart disease within 1 year prior to screening. Managed hypertension is permitted (defined as systolic blood pressure <160 mmHg and/or diastolic blood pressure <100 mmHg).
• Clinically significant history of any central nervous system or psychiatric disease, including transient ischemic attack, stroke, seizure disorder, depression, or behavioral disturbances within 1 year prior to screening.
• Clinically significant gastric emptying abnormality (eg, severe diabetic gastroparesis or gastric outlet obstruction) or have had gastric bypass surgery.
• Clinically significant or unstable history of any hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
• Known or active malignancy, except basal cell carcinoma and cutaneous squamous cell carcinoma.
• Any hospital admission or major surgery within 90 days prior to screening.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, as determined by the Investigator (or designee).
• Fasting C peptide < 0.81 ng/mL.
• Alanine aminotransferase, aspartate aminotransferase, or gamma glutamyl transferase >2 × the upper limit of normal (ULN); or total bilirubin >1.5× ULN. Testing may be repeated once, at the discretion of the Investigator (or designee).
• Uncontrolled hypertriglyceridemia > 500 mg/dL.
• Estimated glomerular filtration rate ≤ 45 mL/minutes/1.73 m2, as calculated using the 2021 Chronic Kidney Disease Epidemiology equation.
• Hemoglobin ≤120 g/L (male) or ≤110 g/L (female).
• QT interval corrected for heart rate using Fridericia's method > 450 msec.
• Positive hepatitis B surface antigen, hepatitis C antibody, human immunodeficiency (HIV 1 and HIV 2) antibodies and p24 antigen.
• Positive pregnancy test.
• Use of insulin, sulfonylureas, GLP-1 agonists, DPP-4 inhibitors, SGLT2 inhibitor and glinides (eg, repaglinide and nateglinide).
• Use of any strong or moderate cytochrome P450 (CYP) 3A4 inducers within 28 days prior to dosing or any strong or moderate CYP3A4 inhibitors within 7 days or 5 half-lives, whichever is longer, prior to dosing (Appendix 5).
• Use of any P glycoprotein inducers within 14 days prior to dosing or any P glycoprotein inhibitors within 5 days or 5 half-lives, whichever is longer, prior to dosing (Appendix 6).
• Use of any carboxylesterase 2 inhibitors within 5 days or 5 half-lives, whichever is longer, prior to dosing (Appendix 7).
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days.
• Positive alcohol test result, or positive urine drug screen (confirmed by repeat) at screening or check in.
• Current drug abuse, defined as the use of any illegal substance or misuse or excessive used of over the counter or prescription drugs; or current alcohol abuse, defined as the inability to stop or control alcohol use, despite adverse social or health consequences.
• Consumption of alcohol, or caffeine containing foods or beverages within 48 hours, or foods and beverages containing grapefruit or Seville oranges within 7 days prior to check in.
• Use of tobacco or nicotine containing products within 1 month prior to screening.
• Receipt or donation of > 1 unit (approximately 450 mL) of blood products within 3 months prior to screening.
• Poor peripheral venous access.
• Participants who, in the opinion of the Investigator (or designee), should not participate in this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Clinical Pharmacology of Miami — Miami

Идентификаторы

NCT: NCT07568678 · HMM0126

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗