A Trial of Hetrombopag in Healthy and Hepatic Impairment Subjects

NCT05088642 | Completed Phase 1

• 1 other identifier: SHR8735-109
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-dose, open-label, phase I clinical study evaluating the PK of hetrombopag in subjects with mild hepatic impairment (Child-Pugh Class A), subjects with moderate hepatic impairment (Child-Pugh Class B), as well as age-, weight-, and gender-matched subjects with normal hepatic function.

Conditions

Sever Aplastic Anaemia

Outcome Measures

Primary Outcomes (3)

• Peak plasma concentration (Cmax)

  0-120 hours post dose

• Area Under the plasma concentration vs time curve (AUC0-120).

  0-120 hours post dose

• Area under the blood concentration vs time curve (AUC0-inf).

  0-infinity

Secondary Outcomes (3)

• Time to Reach Maximum Drug Concentration in Plasma After Single Dose (Tmax)

  0-120 hours post dose

• Half-life Associated With the Terminal Slope (t½)

  0-120 hours post dose

• The number of volunteers with adverse events as a measure of safety and tolerability

  up to Day 6

Study Arms (3)

Mild hepatic impairment (Child-Pugh Class A)

EXPERIMENTAL

Drug: Hetrombopag Olamine Tablet

Moderate hepatic impairment (Child-Pugh Class B)

EXPERIMENTAL

Drug: Hetrombopag Olamine Tablet

Normal hepatic function

EXPERIMENTAL

Drug: Hetrombopag Olamine Tablet

Interventions

Hetrombopag Olamine Tablet DRUG

Hetrombopag Olamine Tablet

Mild hepatic impairment (Child-Pugh Class A); Moderate hepatic impairment (Child-Pugh Class B); Normal hepatic function

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign the informed consent form before the study and fully understand the study content, process, and possible adverse reactions; able to complete the study as required by the clinical study protocol;
• Subjects (and their partners) are willing to adopt effective contraceptive measures from screening to 6 months after the last study administration. See Appendix 1 for specific contraceptive measures;
• Aged 18-65 years (inclusive), male or female;
• Body mass index (BMI = weight (kg)/height2 (m2)): 18-30 kg/m2 (inclusive);
• For subjects with normal hepatic function: normal or abnormal but not clinically significant laboratory findings (hematology, blood biochemistry, urinalysis, and coagulation function);
• For subjects with normal hepatic function: no history of severe primary disorders involving major organs, including but not limited to the gastrointestinal, respiratory, renal, hepatic, neural, hematological, endocrine, neoplastic, immunological, psychiatric, or cardiovascular and cerebrovascular disorders.
• Have not received medication within 4 weeks before screening, or have received stable medication for at least 4 weeks for hepatic impairment and/or other concurrent diseases requiring long-term treatment;
• With Child-Pugh Class A or B hepatic insufficiency caused by prior primary liver disorders (except drug-induced liver diseases).

You may not qualify if:

• Average daily consumption of \> 5 cigarettes within 3 months before screening;
• Allergic constitution, or allergy to any component of hetrombopag olamine tablets;
• Average daily alcohol consumption of \> 15 g for females (e.g., 145 mL of wine, 497 mL of beer, or 43 mL of low-alcohol liquor) and \> 25 g for males (e.g., 290 mL of wine, 994 mL of beer, or 86 mL of low-alcohol liquor) within 3 months before screening;
• History of drug abuse within 3 months before screening;
• Have donated or lost ≥ 400 mL of blood, or have received blood transfusion within 3 months before screening;
• Have undergone major surgery within 6 months before screening, or with incomplete healing of surgical incision;
• History of deep vein thrombosis or other thromboembolic events, or clinical symptoms suggesting thrombophilia;
• Have received TPO receptor agonists (such as eltrombopag and romiplostim) or TPO within 1 month before screening;
• Have taken Chinese herbal medicines or any drug that affects the PK of hetrombopag within 14 days before study administration (see Appendix 2 for drug-drug interaction evaluation);
• Hypertension \[systolic blood pressure (SBP) ≥ 160 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg, confirmed by a re-measurement\];
• Female subjects who are in lactation or have a positive serum pregnancy test result at screening or during the study;
• Abnormal and clinically significant 12-lead ECG results (such as tachycardia/bradycardia requiring pharmacological treatment, second- or third-degree atrioventricular block or QTcF interval prolongation (≥ 470 ms for males, ≥ 480 ms for females) (corrected according to Fridericia's formula), or other clinically significant abnormalities assessed by the clinician);
• Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 calculated using the Modification of Diet in Renal Disease (MDRD) equation;
• Have malignant tumors or history of malignant tumors within 5 years before screening (except treated non-melanoma skin cancer without sign of recurrence and resected cervical intraepithelial neoplasia);
• For subjects with normal hepatic function: have participated in any drug or medical device clinical trials within 3 months before screening; for subjects with hepatic insufficiency: have participated in any drug or medical device clinical trials within 1 month before screening;

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

The First Bethune Hospital of Jilin University

Changchun, Jilin, 130061, China

Location

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: October 12, 2021
• First Posted: October 22, 2021
• Study Start: September 28, 2020
• Primary Completion: December 4, 2020
• Study Completion: December 4, 2020
• Last Updated: October 22, 2021

Record last verified: 2021-10

Locations

CN (1)