A Study to Investigate the Effects of Impaired Hepatic Function on Velzatinib

NCT07859735 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: 301039
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study evaluates the pharmacokinetics (PK), safety, and tolerability of velzatinib in participants with mild, moderate, and severe hepatic impairment (HI) and participants with normal hepatic function.

Conditions

Healthy Participants; Gastrointestinal Neoplasms

Keywords

Healthy participants; Hepatic Impairment; Pharmacokinetics; Velzatinib

Outcome Measures

Primary Outcomes (4)

• Maximum plasma concentration (Cmax)

  Up to 936 hours

• Area under the plasma concentration-time curve extrapolated to infinity AUC(0-inf)

  Up to 936 hours

• Maximum plasma unbound concentration (Cmax,u)

  Up to 936 hours

• Area under the unbound plasma concentration-time curve extrapolated to infinity (AUC[0-inf],u)

  Up to 936 hours

Secondary Outcomes (10)

• Time to maximum observed plasma drug concentration (Tmax)

  Up to 936 hours

• Area under the plasma drug concentration-time curve from time 0 to 48 hours post-dose administration (AUC[0-48])

  Up to 48 hours

• Area under the plasma drug concentration-time curve from time 0 to time of the last quantifiable concentration (AUC[0-last])

  Up to 936 hours

• Terminal elimination rate constant

  Up to 936 hours

• Apparent terminal phase half-life (t1/2)

  Up to 936 hours

Study Arms (4)

Participants with mild hepatic impairment receiving Velzatinib

EXPERIMENTAL

Drug: Velzatinib

Participants with moderate hepatic impairment receiving Velzatinib

EXPERIMENTAL

Drug: Velzatinib

Participants with severe hepatic impairment receiving Velzatinib

EXPERIMENTAL

Drug: Velzatinib

Participants with normal hepatic function receiving Velzatinib

ACTIVE COMPARATOR

Drug: Velzatinib

Interventions

Velzatinib DRUG

Velzatinib will be administered

Also known as: GSK6042981/IDRX-42

Participants with mild hepatic impairment receiving Velzatinib; Participants with moderate hepatic impairment receiving Velzatinib; Participants with normal hepatic function receiving Velzatinib; Participants with severe hepatic impairment receiving Velzatinib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is 18 to 80 years of age, inclusive, at the time of signing the Informed consent form (ICF).
• Participant has stable hepatic function that can be classified into 1 of 4 groups according to the Child-Pugh and National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) classification.
• Participant has stable hepatic function (i.e., no clinically significant change in status according to the investigator's clinical judgment within the preceding 14 days \[e.g., no worsening of clinical signs of HI, or no worsening of total bilirubin or prothrombin by more than 50 percent\]) and those needing treatment are on stable doses of medication.
• Participants with HI may be taking medications, which in the opinion of the investigator, are believed to be therapeutic but do not affect study intervention absorption, distribution, metabolism, excretion (ADME).
• Has no clinically significant and unstable cardiovascular or endocrine findings, except as expected by their pre-existing hepatic condition in the investigator's opinion.
• Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. Participants with chronic disorders such as hypertension and diabetes mellitus can be enrolled, provided those disorders are stable and adequately controlled, but otherwise participants should be considered healthy for their age.

You may not qualify if:

• Participant has a history or evidence of clinically significant hematologic, dermatologic, neurologic, pulmonary, immunologic or atopic (except seasonal allergies), or endocrine disease, or psychiatric disorder (such as psychosis, delusions, or schizophrenia), or other abnormality, that may impact the ability of the participant to participate or potentially confound the study results, or that, in the investigator's opinion, makes the participant unsuitable for the study.
• Semi-supine blood pressure (BP) outside the ranges of 100 to 140 millimeters of mercury (mmHg) for systolic BP and 50 to 90 mmHg for diastolic BP (BP to be measured in triplicate), or a semi-supine pulse rate outside the range of 45 to 90 beats per minute (bpm).
• Participant has symptoms arising from orthostatic hypotension such that there is a decrease in systolic BP of greater than or equal to (\>=) 20 mmHg or in diastolic BP of \>=10 mmHg, or pulse rate increase \>=30 bpm.
• Participant has history of extrahepatic disorders possibly related to etiology of cirrhosis (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, uncontrolled hypertension) (for participants with hepatic impairment).
• Participant has a history of liver or other solid organ transplant including transjugular intrahepatic portosystemic shunt (TIPS) placement (for participants with hepatic impairment).
• Participant has evidence of acute viral hepatitis within 30 days before dosing with study drug.( for participants with hepatic impairment)
• Hepatitis B surface antigen (HBsAg) positive participants are allowed to be enrolled if Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) is below 1000 copies per milliliter in the plasma, at Screening. Participants with HI who are positive for hepatitis C virus antibodies (HCVAb) can be enrolled but must not have detectable hepatitis C virus antibodies (HCV) Ribonucleic acid (RNA) on reflex testing, at Screening (for participants with hepatic impairment).
• The participant has a positive test result for HBsAg or Hepatitis B core antibody (HBcAb) at Screening or within 3 months prior to administration of the study intervention dose (for participants with normal hepatic function).
• The participant has a positive hepatitis C antibody test result at Screening or within 3 months prior to the administration of the study intervention dose (for participants with normal hepatic function).
• Participant has regular alcohol consumption within 6 months prior to the study, defined as an average weekly intake of \>14 units for males and females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliters \[mL\]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• Participant has clinically significant cardiac disease, including second- or third-degree atrioventricular block, clinically significant tachyarrhythmias, or atrial fibrillation/flutter.

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open label study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 1, 2026
• First Posted: October 6, 2026
• Study Start (Estimated): November 10, 2026
• Primary Completion (Estimated): April 25, 2028
• Study Completion (Estimated): April 25, 2028
• Last Updated: October 6, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.