Mass Balance and Biotransformation Study of [14C]LXI-15028 in Humans

A Clinical Trial to Assess Absorption, Metabolism and Excretion of [14C]-LXI-15028 in Chinese Healthy Male Subjects - Mass Balance and Biotransformation Study of [14C]LXI-15028 in Humans

To assess absorption, metabolism and excretion of [14C]-LXI-15028 in Chinese healthy male Subjects following a single oral dose of [14C]LXI-15028 suspension.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Pharmacokinetics of 14C-labeled of LXI-15028
• Intervention / Treatment: Drug: [14C]LXI-15028

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • the First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Chinese healthy male subjects;
• 18 to 45 years of age (inclusive)
• Body mass index (BMI) of 19-26 kg/m2 (inclusive), and body weight not less than 50 kg (inclusive)
• Voluntarily signing the ICF
• Ability to communicate well with the investigator and compliance to complete the trial according to the protocol.

Exclusion Criteria:

• Clinically significant abnormality of physical examination, vital signs, routine laboratory tests (hematology, blood chemistry, coagulation, urinalysis, stool routine + occult blood, and thyroid function), 12-lead ECG, chest CT, and abdomen ultrasound (liver, gallbladder, pancreas, spleen, and kidneys), etc.
• Resting QT interval (QTcF) ≥ 450 ms by 12-lead electrocardiogram (ECG)
• Hepatitis B surface antigen or hepatitis B e antigen test, hepatitis C virus antibody IgG test, human immunodeficiency virus antigen/antibody combination test, or Treponema pallidum antibody test is positive
• Novel coronavirus infection screening shows C-reactive protein is clinically significant abnormality, or COVID-19 nucleic acid test is positive
• Use of any drugs inhibiting or inducing hepatic drug metabolizing enzymes within 30 days before screening;
• Use of any prescription drugs, over-the-counter drugs, Chinese herbal medicines, or dietary supplements such as vitamins and calcium supplements within 14 days before screening;
• History of any clinical critical illness or presence of diseases or conditions that the investigator considers may affect the trial results, including but not limited to diseases of cardiovascular system, circulatory system, respiratory system, endocrine system, nervous system, digestive system, urinary system or blood, immune system, and psychiatric system, especially metabolism and nutrition diseases and gastrointestinal diseases;
• Major surgery within 6 months before screening or incomplete healing of surgical incision, the major surgeries including but not limited to any procedures that have significant risk of hemorrhage, prolonged general anesthesia, open biopsy, or marked traumatic invasive injury;
• Subjects with an allergic constitution (e.g., history of bronchial asthma, allergy to food and pollen, allergy to two or more drugs, or history of allergy), including any previous serious adverse reaction to proton pump inhibitors or potassium-competitive acid blockers (e.g., omeprazole, rabeprazole, lansoprazole, and vonoprazan), or known hypersensitivity to penicillin or cephalosporin antibiotics; or those who may be hypersensitive to the investigational drug or its excipients, as judged by the investigator;
• Hemorrhoids or perianal diseases with regular/current hematochezia, irritable bowel syndrome, and inflammatory bowel disease;
• Habitual constipation or diarrhea;
• Alcoholism or frequent alcohol use within 6 months before screening, i.e., weekly alcohol consumption > 14 units (1 unit = 360 mL of beer or 45 mL of ABV 40% spirit or 150 mL of wine); or positive alcohol breath test result at Screening;
• Daily smoking exceeding 5 cigarettes (≥ 5 cigarettes) within 3 months before Screening, or habitual use of nicotine-containing products and inability to withdraw during the trial period;
• Drug abuse, use of soft drug (e.g., marijuana) within 3 months before screening, or use of hard drug (e.g., cocaine, amphetamines, phencyclidine, etc.) within 1 year before screening; or positive urine drug test at screening;
• Drinking excessive tea, coffee and/or caffeine-containing beverages (over 8 cups, 1 cup = 250 mL) on a daily basis within 3 months prior to screening;
• Inability to avoid intake of grapefruit, bitter orange, starfruit, pithya, mango, and other fruit or fruit juice that may affect the metabolism from 7 days before administration until completion of the study;
• Work with long-term exposure to radioactive conditions; or marked exposure to radioactivity (chest/abdomen CT ≥ 2 times, or other kinds of X-ray examinations ≥ 3 times) or participation in any radioactive labeling trial within 1 year before the trial;
• History of fear of needles and blood, difficult blood sampling, or incapability of tolerating blood sampling via venipuncture;
• Participation in any other clinical trial (including drug and device clinical trials) within 3 months before screening;
• Vaccination within 1 month before Screening or planned vaccination during the trial period;
• Subjects who have a plan for parenthood or sperm donation from the signing of informed consent to 1 year following the completion of the trial, or those who do not agree that subjects and their partners should use strict contraception from the signing of informed consent to 1 year following the completion of the trial;
• Blood loss or blood donation up to 400 mL (≥ 400 mL) within 3 months before Screening, or blood transfusion within 1 month before screening;
• Subjects who have any factors that make them not suitable for participating in this trial, as assessed by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [14C]LXI-15028(n=6-8); Subjects will receive a single oral dose of [14C]LXI-15028 suspension under the fasted state .	Drug: [14C]LXI-15028; [14C]LXI-15028

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mass balance	Mass balance recovery of total radioactivity in urine and fecal samples	approximately 11 days
Metabolite Profiling	To provide plasma, urine and faecal samples for metabolite profiling and structural identification	approximately 11 days
Total radioactivity in plasma PK:Tmax	Time for Cmax	approximately 11 days
Total radioactivity in plasma PK:AUC0-t	Area under the plasma concentration time profile from time 0 to time of the last quantifiable concentration.	approximately 11 days
Total radioactivity in plasma PK:t1/2	Elimination half-life.	approximately 11 days
Total radioactivity in plasma PK:CL/F	Drug clearance	approximately 11 days
Total radioactivity in plasma PK:Vd/F	Apparent volume of distribution following oral administration	approximately 11 days
LXI-15028 and metabolite PK:Cmax	Maximum plasma concentration	approximately 11 days
LXI-15028 and metabolite PK:Tmax	Time for Cmax	approximately 11 days
LXI-15028 and metabolite PK:AUC0-t	Area under the plasma concentration time profile from time 0 to time of the last quantifiable concentration.	approximately 11 days
LXI-15028 and metabolite PK:AUC0-inf	Area under the plasma concentration time profile from time 0 to infinity.	approximately 11 days
LXI-15028 and metabolite PK:t1/2	Elimination half-life.	approximately 11 days
LXI-15028 and metabolite PK:CL/F	Drug clearance	approximately 11 days
LXI-15028 and metabolite PK:Vd/F	Apparent volume of distribution following oral administration	approximately 11 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number of adverse events, which are any untoward medical occurrence regardless of attribution to study drug in a participant who received study drug	approximately 11 days

Collaborators and Investigators

• Sponsor: Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.
• Investigators: Principal Investigator: Liyan Miu, the First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2022
• Primary Completion (Actual): July 21, 2022
• Study Completion (Actual): December 23, 2022

Study Registration Dates

• First Submitted: May 10, 2023
• First Submitted That Met QC Criteria: May 22, 2023
• First Posted (Actual): May 31, 2023

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: NE822201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No