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

• ClinicalTrials.gov Identifier: NCT00698464
• Recruitment Status: Completed
• First Posted: June 17, 2008
• Last Update Posted: December 21, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hepatic Cirrhosis; Alcoholism	Drug: Pasireotide	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: 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
• Study Start Date: July 2008
• Actual Primary Completion Date: April 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pasireotide	Drug: Pasireotide; Single subcutaneous injection of 600 µg of Pasireotide.

Outcome Measures

Primary Outcome Measures :

1. Determination of the pharmacokinetic profile of single dose of pasireotide s.c. injection. [ Time Frame: 5 days ]

Secondary Outcome Measures :

1. Determination of the safety after a single dose of pasireotide s.c. injection [ Time Frame: 5 days ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Virginia

McGuire Research Institute VAMC

Richmond, Virginia, United States, 23249

Belgium

Universite Catholique de Louvain

Brussels, Belgium

Germany

Novartis Investigative site

Berlin, Germany

South Africa

Novartis Investigative Site

George, South Africa

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticlas; Novartis Pharmaceuticlas

More Information

Additional Information:

Novartis Clinical Trial Results on CSOM230B2114 

Publications of Results:

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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00698464
• Other Study ID Numbers: CSOM230B2114
• First Posted: June 17, 2008
• Last Update Posted: December 21, 2020
• Last Verified: November 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Pasireotide; PK profile,; Single dose; Pasireotide subcutaneous injection; Safety; Mild hepatic impaired patients; Moderate hepatic impaired patients; Severe hepatic impaired patients

Additional relevant MeSH terms:

Liver Cirrhosis; Alcoholism; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Liver Diseases; Digestive System Diseases; Pasireotide; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs