GP681 in Volunteers With Hepatic Impairment Compared With Healthy Volunteers

NCT05814926 | Completed Phase 1

• 1 other identifier: GP681-202203
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to test whether mild (Child-Pugh A, score 5-6) and moderate (Child-Pugh B, score 7-9) hepatic impairment affects pharmacokinetics, safety and tolerability of GP681, compared with a control group with normal hepatic function following oral administration of GP681 as single dose.

Conditions

Healthy Volunteers; Hepatic Impairment

Outcome Measures

Primary Outcomes (3)

• Peak plasma concentration (Cmax) of the analyte in plasma after oral administration of GP681

  Day 1 to Day12

• Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration after oral administration of GP681

  Day 1 to Day12

• Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity after oral administration of GP681

  Day 1 to Day12

Secondary Outcomes (5)

• Time to Cmax (Tmax) of the analyte in plasma

  Day 1 to Day12

• Terminal elimination half-life (t1/2) of the analyte in plasma

  Day 1 to Day12

• Apparent Clearance (CLz/F) of the analyte in plasma

  Day 1 to Day12

• Apparent volume of distribution (Vz/F) of the analyte in plasma

  Day 1 to Day12

• Number of participants with drug-related adverse events as assessed by CTCAE v5.0

  Day 1 to Day12

Study Arms (3)

Healthy Control

EXPERIMENTAL

Each healthy participant will receive a single dose of GP681

Drug: GP681

Mild, Child-Pugh A

EXPERIMENTAL

Each participant with Child-Pugh A will receive a single dose of GP681

Drug: GP681

Moderate; Child-Pugh B

EXPERIMENTAL

Each participant with Child-Pugh B will receive a single dose of GP681

Drug: GP681

Interventions

GP681 DRUG

GP681, tablet, oral

Healthy Control; Mild, Child-Pugh A; Moderate; Child-Pugh B

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants，between the ages of 18 and 68 years of age (inclusive) at the time of Screening;
• Body weight ≥50 kg for males, ≥45kg for females, and body mass index (BMI) between18-30 kg/m\^2(inclusive);
• Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions.
• Participants with Hepatic Impairment Only:
• Participants must satisfy the criteria for primary liver disease as evidenced by a Child-Pugh A (score 5-6), B (score 7-9). Treatment-naïve participants for at least 4 weeks before screening can be entered into the study. Unless otherwise stated, participants must have been on stable doses and regimens of the concomitant medication for at least 4 weeks before screening.
• Participants with Normal Hepatic Function Only:
• Healthy participants, between the ages of 18 and 68 years of age (inclusive) at the time of Screening, matched to participants with hepatic impairment with regard to age (+/-10 years), and gender(+/-1 subject);
• Body weight ≥50 kg for males, ≥45kg for females, and body mass index (BMI) between18-30 kg/m\^2(inclusive), matched to participants with hepatic impairment with regard to body weight (+/-25% kg);
• In good health, determined by no clinically significant findings from vital signs, physical examination, 12-lead electrocardiogram (ECG), clinical laboratory evaluations, and other safety examinations at screening, as assessed by the investigator.
• Men must agree to use protocol-specified contraception and also to not donate sperm throughout the study and for at least 3 months after the final dose of study drug
• Adequate hepatic function within 14 days before drug administration defined as: AST or ALT ≤ 1.5 times the upper limit of normal values, total bilirubin within normal limits.

You may not qualify if:

• History of allergic conditions or allergic diseases, or a history of allergic reactions attributed to drugs. Those who cannot follow a uniform diet for special dietary requirements.
• History of seizure，including any febrile seizure, or transient ischemic attack, or any condition that may pre-dispose to seizure (such as prior stroke, brain arteriovenous malformation, brain trauma with requiring hospitalization, and lacunar cerebral infarction).
• Have a malignant tumor or a history of malignant tumor in the 5 years prior to screening (except for patients with non-melanoma skin cancers with no evidence of recurrence, or patients with excised cervical intraepithelial neoplasia).
• Subjects with severe infection, trauma, gastrointestinal surgery or other major surgical operations within 4 weeks before screening;
• Abnormal blood pressure response, or clinically significant abnormal blood pressure assessed by the investigator.
• Having a history of clinically significant ECG abnormalities (history of tachycardia/bradycardia requiring medical therapy, II-III degree atrioventricular block, or QTcF\>450ms for males，\>460ms for females(corrected by Fridericia's formula), or other clinically significant abnormals assessed by the investigator.
• Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2, according to the modification of diet in renal disease equation.
• Those who plan to undergo surgery, or intent to intent to be hospitalized during the trial.
• A positive test for HIV antibody at screening.
• Received any drugs that inhibit or induce the CYP450 enzyme (i.e., phenytoin, rifampin, carbamazepine, fluvoxamine, enoxacin, ticlopidine, gemfibrozil, clopidogrel, clarithromycin, itraconazole, ketoconazole, ritonavir) 4 weeks prior to screening period.
• Received any drugs (including Chinese herbal medicine, vitamins and supplements) within 14 days or 5-half-lives (which is longer) prior to dosing;
• Participation in another clinical trial within 3 months before dosing.
• Those who have lost blood or donated up to 200 mL within 3 months before dosing, or those who plan to donate blood within 1 month after the end of this study.
• Smoking more than 5 cigarettes per day within 3 months prior to screening，or who cannot stop using any tobacco products during the study period.
• Average weekly intake of alcohol is more than 14 units alcohol (1 units ≈ 360 mL beer, or 45 mL spirits with 40% content, or 150 mL wine) within the 6 months prior to dosing, or a positive ethanol breath test at screening.

Sponsors & Collaborators

• Jiangxi Qingfeng Pharmaceutical Co. Ltd.: lead

Study Sites (1)

Beijing You'an Hospital, Beijing Medical University

Beijing, Beijing Municipality, 100069, China

Location

Study Officials

• Haibin Yu

  Beijing YouAn Hospital

  PRINCIPAL INVESTIGATOR

• Bin Xu

  Beijing YouAn Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2023
• First Posted: April 18, 2023
• Study Start: April 26, 2023
• Primary Completion: August 3, 2023
• Study Completion: October 20, 2023
• Last Updated: November 15, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)