A Study of Ipatasertib in Participants With Mild, Moderate or Severe Hepatic Impairment Compared to Healthy Participants

Hepatic Insufficiency Clinical Trial

Official title:

A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Ipatasertib in Subjects With Mild, Moderate or Severe Hepatic Impairment Compared to Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03341884
• Other study ID #: GP40200
• Status: Completed
• Phase: Phase 1
• Start date: November 9, 2017
• Est. completion date: June 26, 2018

Study information

• Verified date: November 2019
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1 study evaluating the pharmacokinetics, tolerability and safety of a single dose of ipatasertib in participants with mild, moderate or severe hepatic impairment compared to healthy participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: June 26, 2018
• Est. primary completion date: June 26, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• In good health (except for specific inclusion criteria related to hepatic impairment), as determined by the Investigator, based on no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram, and vital signs

• Females will not be pregnant or breastfeeding, and must be either postmenopausal or agree to use a study-approved method of contraception from the time of signing the informed consent until 30 days after discharge

• Males will either be sterile or agree to use male condom with spermicide from check-in (Day -1) until 90 days following the dose of study drug

Additional Inclusion Criteria for Healthy Subjects Only:

• Liver enzyme tests must be less than or equal to the upper limits of normal

Additional Exclusion Criteria for Hepatic Impaired Subjects Only:

• Hepatic impairment must have a Child-Pugh score of 5 to 6 (mild), 7 to 9 (moderate), or 10 to 15 (severe) and have stable hepatic insufficiency within 1 month prior to Screening

Exclusion Criteria:

• History of ulcerative colitis or stomach or intestinal surgery or resection

• History of unstable diabetes mellitus

• History of alcoholism or drug addiction within 1 year prior to Check-in (Day -1)

• Use of oral, implantable, transdermal, or injectable contraceptives from the time of signing the informed consent (females only) or 10 days prior to Check-in through 45 days after the dose administration

• Poor peripheral venous access

• Receipt of blood products within 2 months prior to check-in

Additional Exclusion Criteria for Healthy Subjects Only:

• Use of any tobacco- or nicotine-containing products within 6 months prior to check-in and during the entire study

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder

Additional Exclusion Criteria for Hepatic Impaired Subjects Only:

• Any evidence of progressive liver disease that has worsened or is worsening within 1 month prior to the screening visit

• Participant has shown evidence of hepatorenal syndrome

• Ascites requiring paracentesis

• Participant has required treatment for GI bleeding within 12 months prior to Check-in

• Participant has required additional medication for hepatic encephalopathy within the 12 months (6 months for severe hepatic impairment) prior to check-in

• Total bilirubin levels >6 mg/dL

Related Conditions & MeSH terms

• Hepatic Insufficiency
• Liver Failure

Intervention

Drug:
• Ipatasertib
A single oral dose of 100 mg ipatasertib will be administered.

Locations

Country	Name	City	State
United States	New Orleans Center for Clinical Research	Knoxville	Tennessee
United States	Clinical Pharmacology of Miami, Inc.	Miami	Florida
United States	American Research Corporation Inc.	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration-Time Curve (AUC) from 0 to Infinity (AUC0-inf) of Ipatasertib	AUC0-inf is defined as AUC extrapolated from Hour 0 to infinity of ipatasertib in the plasma.	up to Day 15
Primary	Maximum Observed Plasma Concentration (Cmax) of Ipatasertib	Maximum observed concentration of ipatasertib as determined by measuring drug concentration in blood samples over time.	up to Day 15
Secondary	Percentage of Participants with Treatment-Emergent Adverse Events (AE)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	up to Day 15
Secondary	Time to Reach Maximum Observed Concentration (tmax) of Ipatasertib	Time from dose administration to observed maximum serum concentration for ipatasertib as determined by measuring drug concentration in blood samples over time.	up to Day 15
Secondary	AUC from 0 to last measurable concentration (AUC0-t)	Area under the plasma concentration-time curve from Hour 0 to the last measurable concentration of ipatasertib.	up to Day 15
Secondary	Half-life (t1/2) of Ipatasertib	Half-life of ipatasertib is the time elapsed for the drug concentration to decrease by half as determined by measuring drug concentration in blood samples over time.	up to Day 15
Secondary	Apparent Plasma Clearance (CL/F) of Ipatasertib	Apparent clearance (CL/F) of ipatasertib, where CL is clearance and F is bioavailability (relative amount of extravascularly-administered drug that reaches systemic circulation unchanged). Determined by measuring drug concentration in blood samples over time.	Up to Day 15
Secondary	Apparent Volume of Distribution (V/F) of Ipatasertib	Apparent volume of distribution (V/F) during the terminal phase of ipatasertib.	up to Day 15