The Absorption, Metabolism and Excretion of [14C]D-0316 in Human

A Single-center, Open-label, Single-dose Phase I Study to Investigate the Absorption, Metabolism and Excretion of [14C]D-0316 After a Single Oral 75mg/50µCi Dose in Healthy Chinese Male Subjects

This is a single-center, open-label, single-dose phase I study to investigate the absorption, metabolism and excretion of [14C] D-0316 in healthy Chinese male subjects. The study will be conducted into two steps：Firstly, 2 subjects are enrolled in to participate in the pilot study to grope for the completion date of plasma, urine and feces sampling on the 3rd day post-dose and onwards. Then, the collection time of blood and excreta samples (urine and feces) from the subsequent 2-4 subjects will be adjusted according to the pilot study

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced or Metastatic Non-small Cell Lung
• Intervention / Treatment: Drug: [14C]D-0316 suspension

Detailed Description

Subjects who had signed informed consent and meet inclusion criteria and no exclusion criteria are admitted to Phase I Clinical Unit two days prior to dosing (D-2). On the morning of Day 1 before dosing, subjects will be transferred to nuclear medical ward. And after an overnight fast of at least 10 h, subjects will receive a single oral dose of 75 mg (50 μCi) of [14C]D-0316 as an oral suspension. Then, after two days of the dosing, subjects will be transferred back to Phase I Clinical Unit ward and confined to this unit until blood or excreta sampling and safety monitoring at the designated time points or intervals are complete

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• healthy male volunteers between the ages of 18 to 50 years old；
• Body weight >=50 kg, Body mass index (body weight(kg)/hight2(m2)) between 19 and 26 kg/m2；
• Normal physical findings, clinical laboratory values, vital signs and 12-lead ECG, or any abnormality that is non-clinically significant;
• Male subjects of reproductive potential with partners will be instructed to, and must be willing to practice a highly effective method of birth control for the duration of the study and continuing 1 year after discontinuing treatment with the investigational product. Highly effective methods of birth control include using condom, contraceptive sponge, contraceptive gel, contraceptive film, intrauterine device, oral or injectable contraceptive pill, hypodermic implants or others；
• Must understand, and voluntarily sign the informed consent, comply with the requirements of the study.

Exclusion Criteria:

• History of or current clinically significant cardio, pulmonary, endocrine, metabolism, renal, hepatic, gastrointestinal, dermatology, infection, hematology, neurological, mental disease or disorder;
• Positive test for HBsAg, HBeAg, anti-HCV, anti-HIV or syphilis antibody;
• History of syncope / needle syncope and intolerable intravenous indwelling needle;
• History of clinically significant disease or infection within 1 month before entering the study;
• Abnormality in blood pressure, including hypertensive BP (SBP>=140 mmHg, or DBP >=90 mmHg), or hypotensive BP(SBP<90 mmHg, or DBP <=55 mmHg), Pulse rate<55 bpm or >100 bpm;
• Long-QT syndrome or family history of it, or QTcB interval > 450 ms; intraventricular blocks or left/right bundle branch block or QRS>120ms; frequent ventricular ectopic beats (any 10s ECG ventricular premature beat >= 1 in screening period); or abnormal resting heart rate (> 100 bpm);
• Received any drug within 14 days before taking the investigational drug, including any prescription drug, OTC drug, herbal drug or health care products, except for vitamins and paracetamol；
• History of or current swallowing disorder, active gastrointestinal diseases, or other diseases that significantly affect absorption, distribution, metabolism and excretion of drugs;
• Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease;
• Hemorrhoids or perianal disease with regular/perianal bleeding;
• Allergies, have allergies to two or more drugs or foods; or have known allergies to the components of the drug;
• Participated in other clinical trials within 3 months before screening;
• The subjects participated in the clinical trial of radioactive labeling within one year before taking the medicine;
• Significant radiation exposure within one year prior to drug administration (more than one exposure from chest X-ray, CT scan, or barium meal examination and radiation-related occupations);

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]D-0316; To investigate the absorption properties, as well as to evaluate the mass balance and elucidate the pathways of biotransformation after a single oral dose (75mg, 50µCi) of [14C]D-0316 to healthy Chinese male subjects

Drug: [14C]D-0316 suspension; Before administration, the drug preparation was placed at room temperature, and 40ml drinking water was added into each bottle to prepare suspension for the subjects to take. 40ml pure water was injected again. After washing the container, the subjects took orally. Repeat the previous step, and then used 160ml purified water. After the administration container was moistened for several times, the subjects took all the moistening lotion. Pay attention not to splash the liquid during mixing outside the bottle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radioactivity concentration of each plasma sample	Use liquid scintillation counter or accelerator mass spectrometry to evaluate radioactivity concentration of each plasma（DPM/ml) sample	Day 1-Day85
Radioactivity concentration of each urine samples	Use liquid scintillation counter or accelerator mass spectrometry to evaluate radioactivity concentration of each urine（DPM/ml) sample	Day-1-Day85
Radioactivity concentration of each feces sample	Use liquid scintillation counter or accelerator mass spectrometry to evaluate radioactivity concentration of each feces（DPM/ml) sample	Day-1-Day85
Total recovery of radioactivity in urine and feces	Calculate the total radioactivity in urine and feces based on the radioactivity concentration of each sample	Day-1-Day85
Identification of metabolites in plasma, urine and fecal samples	LC-MS/MS was used to identify the main metabolites in plasma, urine and feces, and finally to provide the main biotransformation pathway of CM082 in human body	Day-1-Day85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters of unlabeled D-0316 and metabolite D-0865	To determine the plasma concentrations of D-0316 with validated LC-MS/MS method for obtaining its pharmacokinetics parameters	Day-1-Day85
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	According to CTCAE v4.03, the number and frequency of adverse events after a single dose of test drug were assessed	Day-14-Day85

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.
• Investigators: Principal Investigator: Feng Shao, Ph D, Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine; Principal Investigator: Wei Liu, M.A, Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2020
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: July 3, 2020
• First Submitted That Met QC Criteria: July 3, 2020
• First Posted (Actual): July 9, 2020

Study Record Updates

• Last Update Posted (Actual): June 2, 2021
• Last Update Submitted That Met QC Criteria: May 31, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: IBIO-105

Drug and device information, study documents

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