Clinical trial NCT00698464: Pharmacokinetics and Safety of Single Subcutaneous Pasireotide (SOM230) in Subjects With Varying Degrees of Hepatic Function
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Cirrhosis
Alcoholism
Keywords: Pasireotide
PK profile,
Single dose
Pasireotide subcutaneous injection
Safety
Mild hepatic impaired patients
Moderate hepatic impaired patients
Severe hepatic impaired patients
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-06-17
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility 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.

Primary outcomes:
measure: Determination of the pharmacokinetic profile of single dose of pasireotide s.c. injection.
timeFrame: 5 days
Secondary outcomes:
measure: Determination of the safety after a single dose of pasireotide s.c. injection
timeFrame: 5 days
Other outcomes:
Locations:
city: Richmond
country: United States
facility: McGuire Research Institute VAMC
state: Virginia
city: Brussels
country: Belgium
facility: Universite Catholique de Louvain
city: Berlin
country: Germany
facility: Novartis Investigative site
city: George
country: South Africa
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticlas
name: Novartis Pharmaceuticlas
role: STUDY_DIRECTOR
References:
citation: 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.