ADME Study of [14C]- Larotinib in Healthy Male Subjects

Single Dose Absorption, Distribution, Metabolism, and Excretion Study of [14C] - Larotinib in Healthy Male Participants

Study to Evaluate the Mass Balance and Biotransformation of Single Dose [14C]-Larotinib（Z650）in healthy male subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Male Volunteers
• Intervention / Treatment: Drug: [14C]-Larotinib

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

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy males, 18 to 45 years at the time of screening.
• Weight>50 kg, Body mass index (BMI) is 19~26 kg/m2
• signing of informed consent
• Volunteers are able to communicate well with the investigators and be able to complete the trial according to the process

Exclusion Criteria:

• physical examination, vital signs, routine laboratory tests 12-lead ECG, Chest X-ray ,ophthalmologic examination, abdominal B-ultrasound and other abnormalities and clinical significance.
• positive testing for HIV, HBsAg, HBeAb, HCVAb or Syphilis antibody.
• C- reactive protein (CRP) abnormalities are clinically significant or New Coronavirus nucleic acid positive.
• Screening for use of any clinical trial drug within the first 3 months or withdrawal time shorter than the 7 half-life period of the trial drug at enrollment, whichever is the longest of the two;
• CYP3A4, CYP2C8 , CYP2C9 and p-gp inducers or inhibitors were taken within 28 days before screening
• Use of any prescription or over-the-counter drug, any vitamin product, health care drug or Chinese herbal medicine within 14 days prior to screening;
• clinical symptoms or diseases of the heart;supraventral or ventricular arrhythmia with clinical significance that requires treatment or intervention; QTcF>450ms at screening stage
• Patients who had undergone major surgery or whose surgical incision was not completely healed within 6 months before the screening period;Major surgery includes, but is not limited to, any surgery with a significant risk of bleeding, prolonged general anesthesia, or an open biopsy or significant traumatic injury;
• Significant clinical bleeding symptoms or definite bleeding tendency occurred within 3 months before screening
• Screening for abdominal fistula, gastrointestinal perforation or abdominal abscess in the first 6 months;
• Hemorrhoids or perianal diseases with regular/bleeding in the stool;Patients with gastrointestinal dysfunction, such as irritable bowel syndrome and inflammatory bowel disease, may be affected by drug absorption as determined by researchers;
• Allergic persons,
• A history of any clinically serious illness or condition, including but not limited to circulatory, endocrine, nervous, digestive, urinary, or blood, immune, mental, and metabolic diseases, that the investigator considers to be likely to affect the results of the study;
• Habitual constipation or diarrhea;
• Heavy drinking or regular drinking in the six months preceding the screening period
• Those who had smoked more than 5 cigarettes per day on average in the 3 months before the screening period or habitually used nicotine-containing products and were unable to quit during the test period;
• Substance abuse or use of soft drugs (e.g., marijuana) in the 3 months prior to the screening period or use of hard drugs (e.g., cocaine, amphetamines, phenylcyclohexidine, etc.) in the 1 year prior to the screening period;Or screening for positive urine drug abuse (drug) tests;
• habitual consumption of grapefruit juice or excessive consumption of tea, coffee and/or caffeinated beverages and failure to abstain during the study period;
• Those with a history of fainting needle or blood, have difficulty in blood collection or cannot tolerate vein puncture for blood collection;
• Workers engaged in conditions requiring long-term exposure to radioactivity;Or have significant radiation exposure (≥2 chest/abdomen CT, or ≥3 other types of X-ray examinations) within 1 year before the test or have participated in the radiopharmaceutical labeling test;
• Those who have lost blood or donated up to 400 mL within 3 months before the screening period, or those who have received blood transfusion, or those who plan to donate blood within 3 month after the end of this test;
• Those who have been vaccinated within 1 month before screening or those who plan to be vaccinated during the trial period;
• Having family planning during the trial period and within 12 months after the last use of the drug, or not agreeing that subjects and their spouses should take strict contraceptive measures during the trial period and within 12 months after the last use of the drug;
• As determined by the investigator, the subject has other factors that are not suitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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]-Larotinib; Patients will receive single dose of [14C]-Larotinib (Suspension, 350mg/100μCi).	Drug: [14C]-Larotinib; Patients will receive single dose of orally [14C]-Larotinib on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative excretion of 14C-labeled drug-related material (radioactivity in plasma, urine and fecal samples)	Percent (%) of each radiolabeled drug-related material (parent and each metabolite) will be determined in plasma, urine and feces.	up to 15 days
Identification of the Proportion of different metabolites to determine biotransformation pathway of Larotinib	Proportion of different metabolites(Larotinib and main metabolites） .	up to 15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitive analysis of the concentrations of Larotinib in plasma using the validated LC-MS/MS to obtain pharmacokinetic data	The concentrations of Larotinib in plasma	up to 15 days
Adverse events	Adverse events assessed by CTCAE v5.0.	up to 22 days

Collaborators and Investigators

• Sponsor: Sunshine Lake Pharma Co., Ltd.
• Investigators: Principal Investigator: Liyan Miao, MD, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2021
• Primary Completion (Actual): January 10, 2022
• Study Completion (Actual): January 10, 2022

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: September 26, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: Z650-HV-106

Drug and device information, study documents

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