Status:
COMPLETED
PK and Safety of Midostaurin in Subjects With Impaired Hepatic Function and Subjects With Normal Hepatic Function
Lead Sponsor:
Novartis Pharmaceuticals
Conditions:
Hepatic Impairment
Eligibility:
All Genders
18-70 years
Phase:
PHASE1
Brief 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 pharmacokineti...
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 h...
Eligibility Criteria
Inclusion
- Key
- Adult male or female subjects age 18-70 years
- Negative serum beta-hCG pregnancy test for all women prior to starting treatment
- Normal vital signs, body weight, BMI and laboratory test results
- Willing to comply with dietary, fluid and lifestyle restrictions
- Able to communicate well with the Investigator and comply with the requirements of the study.
- Additional Inclusion Criteria for hepatic impaired subjects
- Physical signs consistent with hepatic impairment
- CPC score consistent with degree of hepatic impairment
- Serum creatinine \<=2xULN
- ANC \>1000cells/mm3, hemaglobin \>9g/dL, platelet count \> 50,000/mm3 (group 2-3 only)
- Key
Exclusion
- Significant neurologic or psychiatric disorder which could compromise participation in the study.
- History of: seizures requiring anti-convulsant therapy; unstable COPD; GI or rectal bleeding 3 weeks prior to study start; Myocardial Infarction within 12 months; unstable or poorly controlled angina or other clinically significant heart disease; clinically significant urinary obstruction or difficulty voiding; clinically significant ECG abnormalities or long QT-interval syndrome; pancreatic injury or pancreatitis
- Concurrent severe / uncontrolled medical conditions
- Significant illness within 2 weeks prior to dosing or hospitalisation within 4 weeks prior to dosing
- Any surgical or medical condition that may significantly affect absorption, distribution, metabolism or excretion of drugs
- Clinically significant ECG abnormalities at screening
- Cotinine levels greater than 500ng/mL (group 1-3) or smokers not willing to limit tobacco or nicotine products equivalent to 10 cigarettes per day (group 4 and 5) for 1 week prior to dosing and throughout hospital confinement
- Consumption of alcohol within 3 days (group 1-3) or within 2 days (groups 4 and 5) prior to dosing or during the study.
- Administration of CYP3A4/5 or P-gp inducing or inhibiting drugs within 14 days prior to dosing or during the study
- Sexually active males unless they use condom during intercourse while taking midostaurin and for at least 3 months after the last exposure to drug.
- Use of any prescription drug within 2 weeks or over the counter medication within 72 hours prior to dosing
- Consumption of grapefruit, grapefruit juice, Seville oranges, start fruit / juice within 72 hours prior to dosing
- Additional exclusion criteria for healthy controls
- Clinical evidence of liver disease or liver injury
- Positive HBsAg or Hep C test result
- Additional exclusion criteria for hepatic impairment subjects
- Symptoms or history of \>=G3 hepatic encephalopathy; surgical portosystemic shunt
- PTT \>2.5xULN; INR \>3; Total bilirubin \>6mg/dL
- Evidence of progressive liver disease within 4 weeks prior to starting study
- Clinical evidence of severe \>=G3 ascites (groups 2 and 3)
Key Trial Info
Start Date :
March 7 2011
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 9 2020
Estimated Enrollment :
43 Patients enrolled
Trial Details
Trial ID
NCT01429337
Start Date
March 7 2011
End Date
May 9 2020
Last Update
May 12 2021
Active Locations (7)
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1
American Research Corporation Inc
San Antonio, Texas, United States, 78215
2
Novartis Investigative Site
Brussels, Belgium, 1200
3
Novartis Investigative Site
Sofia, Bulgaria, 1618
4
Novartis Investigative Site
Berlin, Germany, 14050