Pharmacokinetics and Safety of Single Subcutaneous Pasireotide (SOM230) in Subjects With Varying Degrees of Hepatic Function

A Phase I, Open-label, Multi-center, Single Dose Study to Evaluate the Pharmacokinetics and Safety of Subcutaneous Pasireotide (SOM230) in Subjects With Varying Degrees of Hepatic Function

The purpose of this study is to evaluate the effect of varying degrees of hepatic function (Child-Pugh classification) on the pharmacokinetics and safety of pasireotide s.c. in subjects.

Study Overview

• Status: Completed
• Conditions: Alcoholism; Hepatic Cirrhosis
• Intervention / Treatment: Drug: Pasireotide

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Université Catholique de Louvain
• Germany
  • Berlin, Germany
    • Novartis Investigative Site
• South Africa
  • George, South Africa
    • Novartis Investigative Site
• United States
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire Research Institute VAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

Common Inclusion criteria for all subjects:

• Male or female subjects between 18 and 75 years of age, inclusive.
• Vital signs at screening and baseline which are within normal ranges.
• Subjects must have a BMI between 20 kg/m2 and 30 kg/m2.

Inclusion Criteria for cohort 1:

• Generally healthy subjects as determined by past medical history, physical examination, vital signs, electrocardiogram and standard laboratory tests at screening.

Inclusion Criteria for cohort 2-4:

• Subjects with confirmed cirrhosis by at least one of the following criteria:
• Histologically by prior liver biopsy showing cirrhosis.
• Clinically by physical examination, and/or laboratory data, and/or liver imaging, and/or endoscopic findings.

Exclusion criteria:

Common Exclusion criteria for all subjects:

• Donation or loss of 400 mL or more of blood within eight weeks prior to dosing.
• Subjects with additional active malignant disease within the last five years (with the exception of non-melanoma skin cancers that were not metastatic and have been treated curatively).
• Subjects with abnormal clinical laboratory values (except the clinical laboratory values linked to hepatic dysfunction).
• Any surgical or medical condition that may interfere with the conduct of the study, may jeopardize the subject in case of participation in the study or may significantly alter the absorption, distribution, metabolism or excretion of drugs.
• History of immunocompromise, including a positive HIV test result (ELISA and Western blot). A HIV test will not be required; however, previous medical history will be reviewed
• Female subjects who are pregnant (positive pregnancy test at screening or at baseline) or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control.

Exclusion Criteria for cohort 1:

• Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests.
• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result (antibody positive subjects will be allowed if non-viremic).

Exclusion Criteria for cohort 2-4:

• Symptoms or history of encephalopathy (Stage III or worse) within three months prior to dosing.
• Clinical evidence of severe ascites. Exclusion criteria

Common Exclusion criteria for all subjects:

• Donation or loss of 400 mL or more of blood within eight weeks prior to dosing.
• Subjects with additional active malignant disease within the last five years (with the exception of non-melanoma skin cancers that were not metastatic and have been treated curatively).
• Subjects with abnormal clinical laboratory values (except the clinical laboratory values linked to hepatic dysfunction).
• Any surgical or medical condition that may interfere with the conduct of the study, may jeopardize the subject in case of participation in the study or may significantly alter the absorption, distribution, metabolism or excretion of drugs.
• History of immunocompromise, including a positive HIV test result (ELISA and Western blot). A HIV test will not be required; however, previous medical history will be reviewed
• Female subjects who are pregnant (positive pregnancy test at screening or at baseline) or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control.

Exclusion Criteria for cohort 1:

• Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests.
• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result (antibody positive subjects will be allowed if non-viremic).

Exclusion Criteria for cohort 2-4:

• Symptoms or history of encephalopathy (Stage III or worse) within three months prior to dosing.
• Clinical evidence of severe ascites.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pasireotide	Drug: Pasireotide; Single subcutaneous injection of 600 µg of Pasireotide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determination of the pharmacokinetic profile of single dose of pasireotide s.c. injection.	5 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Determination of the safety after a single dose of pasireotide s.c. injection	5 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticlas, Novartis Pharmaceuticlas

Publications and helpful links

General Publications

• Horsmans Y, Hu K, Ruffin M, Wang Y, Song D, Bouillaud E, Wang Y, Mazur D, Botha FP, Heuman DM. Effect of hepatic impairment on the pharmacokinetics of pasireotide (SOM230): results from a multicenter phase I study. J Clin Pharmacol. 2012 Apr;52(4):552-8. doi: 10.1177/0091270011400072. Epub 2012 Jan 26.

Helpful Links

• Novartis Clinical Trial Results on CSOM230B2114

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: June 11, 2008
• First Submitted That Met QC Criteria: June 13, 2008
• First Posted (Estimate): June 17, 2008

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Safety; Single dose; Pasireotide; PK profile,; Pasireotide subcutaneous injection; Mild hepatic impaired patients; Moderate hepatic impaired patients; Severe hepatic impaired patients
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Digestive System Diseases; Pathologic Processes; Alcohol-Related Disorders; Substance-Related Disorders; Liver Diseases; Fibrosis; Alcoholism; Liver Cirrhosis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pasireotide
• Other Study ID Numbers: CSOM230B2114