NCT01429337

PK and Safety of Midostaurin in Subjects With Impaired Hepatic Function and Subjects With Normal Hepatic Function

An Open-label, Parallel Group, Phase I Study to Assess the Pharmacokinetics and Safety of Midostaurin in Subjects With Impaired Hepatic Function and Subjects With Normal Hepatic Function.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

The purpose of this international study was to assess the effect of varying degrees of impaired hepatic function compared to a normal hepatic function (Child-Pugh classification) on the pharmacokinetics and safety of midostaurin.

Detailed description

Midostaurin was developed for the treatment of patients with hematological and nonhematological malignancies. However, disease complications and various co-medications made it difficult to perform a hepatic impairment study in the targeted patient population. Metabolism and elimination of midostaurin predominantly occurs in the liver. Patients with impaired hepatic function may have a higher risk to have a decreased elimination or metabolism of midostaurin which may lead to increased systemic exposure or toxicity, hence understanding the impact of an impaired hepatic function on midostaurin PK is important. Cumulative safety data from over 900 subjects exposed to midostaurin showed that the drug was well tolerated in patients and in healthy subjects, thus, it was appropriate and justifiable to study midostaurin in subjects with varying degrees of hepatic impairment. Due to the difficulty in enrolling subjects with severe hepatic impairment, an interim analysis was performed when all mild and moderate hepatic impaired subjects, and the respective control subjects, had completed the trial, in order to obtain interim results on the PK and safety of midostaurin in patients with mild and moderate hepatic impairment. The protocol was amended in April 2018 to make the inclusion / exclusion criteria more fitting with enrolling the severe hepatic impairment group. The final study analysis was performed when all severe hepatic impaired subjects, and the matching controls, had completed the study.

Conditions

• Hepatic Impairment

Interventions

Type	Name	Description
DRUG	Midostaurin	Midostaurin 25 mg soft gelatin capsules (2 capsules). The midostaurin capsules will be administered orally with 240 mL of non-carbonated water in the morning (between 8-10 AM), and in the evening (after a 12 hour break) from Day 1 to Day 6. On Day 7, midostaurin will be administered in the morning only (between 8-10 AM).
DRUG	Midostaurin	Midostaurin 25 mg soft gelatin capsules (2 capsules). The midostaurin capsules will be administered orally with 240 mL of non-carbonated water in the morning (between 8-10 AM) on Day 1 only.

Timeline

• Start date: 2011-03-07
• Primary completion: 2020-04-13
• Completion: 2020-05-09
• First posted: 2011-09-07
• Last updated: 2021-05-12

Locations

7 sites across 6 countries: United States, Belgium, Bulgaria, Germany, Lithuania, Romania

Regulatory

• FDA-regulated drug study