A Phase I Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Subcutaneous UBT38006 Injection in Healthy Adult Males

Official title

A Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Subcutaneous Administration of UBT38006 Injection in Healthy Adult Male Subjects

Overview

This study is a single-center, randomized, double-blind, placebo- and active-controlled, parallel-group, single-ascending dose (SAD) design. Insulin degludec and insulin icodec injection serves as the active control and is administered in an open-label manner. The study will be conducted across 6 cohorts, comprising 4 dose-escalation cohorts of UBT38006 (1, 3, 6, and 12 nmol/kg) ， 1 active control cohort of insulin degludec (0.4 U/kg \[2.4 nmol/kg\]) and 1 active control cohort of insulin icodec (1.25 U/kg \[7.5 nmol/kg\]). The safety and tolerability (including local tolerability) as well as the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of single subcutaneous doses of UBT38006 injection will be evaluated in healthy adult male participants. In Cohort 1 (1 nmol/kg), participants will be randomized in a 4:1 ratio to receive UBT38006 injection or placebo. In Cohorts 2-4 (3, 6, and 12 nmol/kg), participants will be randomized in an 8:2 ratio to receive the corresponding dose of UBT38006 injection or placebo. Participants in Cohort 5 (insulin degludec active control) will receive 0.4 U/kg (2.4 nmol/kg) insulin degludec injection. Participants in the insulin icodec cohort received a subcutaneous injection of insulin icodec at a dose of 1.25 U/kg(7.5 nmol/kg). Cohorts 1-4 will follow a double-blind design, while Cohort 5 and insulin icodec cohort will be open-label.

Interventions

• Drug UBT38006
  Ascending single doses - 4 dose levels
• Drug Placebo
  Ascending single doses - 4 dose levels
• Drug Insulin Degludec Injection
  single subcutaneous injection
• Drug Insulin Icodec Injection
  single subcutaneous injection

Primary outcome measures

• incidence of adverse events (AEs), adverse drug reactions (ADRs), serious adverse events (SAEs), etc,.. [Time frame: Baseline to Day43]

Secondary outcome measures (8)

• GIRmax [Time frame: Baseline to Day43]
• Tmax,GIR [Time frame: Baseline to Day43]
• AUCGIR [Time frame: Baseline to Day43]
• Cmax [Time frame: Baseline to Day43]
• Tmax [Time frame: Baseline to Day43]
• t1/2z [Time frame: Baseline to Day43]
• AUC0-t [Time frame: Baseline to Day43]
• AUCGIR,0-t [Time frame: Baseline to Day43]

Eligibility criteria

Inclusion criteria

• Aged 18-45 years (inclusive) at the time of informed consent form (ICF) signing;
• Sex: Male;
• Body weight ≥50.0 kg and body mass index (BMI) between 19.0-24.0 kg/m² (BMI = weight \[kg\] / height² \[m²\]), inclusive, at Screening;
• Fasting plasma glucose (FPG) between 3.9-6.1 mmol/L (exclusive of boundary values) at Screening; 2-hour plasma glucose <7.8 mmol/L on oral glucose tolerance test (OGTT) at Screening; insulin release test (IRT) results normal, or abnormal but judged by the Investigator as not clinically significant (NCS)at Screening; glycated hemoglobin (HbA1c) ≤6.0% at Screening;
• The subject (including his partner) is willing to use adequate and effective contraception voluntarily from Screening through 3 months after administration of the investigational medicinal product (IMP) (see Appendix 2 for details), and has no plan to donate sperm within 3 months after IMP administration;
• The subject is able to communicate well with the Investigator, has adequate understanding of this study, participates voluntarily, understands and complies with all study requirements, and provides written informed consent.

Exclusion criteria

• History of severe hypersensitivity (e.g., allergy to three or more allergens, allergic asthma involving the lower respiratory tract, or allergy requiring systemic corticosteroid therapy) or known hypersensitivity to any component of the investigational medicinal product;
• History of severe or currently clinically significant disease/condition (including but not limited to diseases of the nervous, cardiovascular, respiratory, hematologic and lymphatic, immune, renal, hepatic, gastrointestinal, metabolic, and skeletal systems, history of malignancy, or neurological or psychiatric disease/condition);
• History of orthostatic hypotension, syncope, or amaurosis, or first-degree relative with history of diabetes mellitus;
• Laboratory abnormalities (hematology, blood chemistry, coagulation function, thyroid function, urinalysis, stool routine, etc.) at Screening that are judged by the Investigator as clinically significant;
• Positive insulin autoantibody (IAA) at Screening;
• Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), HIV antibody, or Treponema pallidum antibody at Screening;
• History of drug abuse, or positive urine drug screen prior to randomization;
• Clinically significant abnormalities on physical examination, electrocardiogram (ECG), or vital signs (body temperature, pulse, blood pressure);
• Use of insulin-containing agents within 3 months prior to dosing, or use of any other medication (including traditional Chinese medicine, over-the-counter drugs, etc.) within 30 days prior to dosing;
• Vaccination with any vaccine within 1 month prior to dosing;
• History of surgery within 3 months prior to dosing, or planned surgery during the entire study period;
• History of blood loss or blood donation exceeding 200 mL within 3 months prior to dosing (calculated from the day before dosing);
• Hemoglobin below the lower limit of normal (LLN);
• Participation in other interventional clinical trials within 3 months prior to dosing (except for subjects who only underwent screening but were not enrolled, or were enrolled but did not receive treatment);

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Hospital of Anhui Medical University — Hefei

Identifiers

NCT: NCT07630233 · TUL-UBT38006（Ⅰ-1）202509

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗