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

Genentech

Status and phase: Completed; Phase 1

Conditions: Hepatic Insufficiency

Treatments: Drug: Ipatasertib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03341884

GP40200

Details and patient eligibility

About

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.

Enrollment: 29 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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29 participants in 4 patient groups

Normal Hepatic Function

Experimental group

Description:

Participants with normal hepatic function will be administered a single oral dose of ipatasertib (100 mg).

Treatment:

Drug: Ipatasertib

Mild Hepatic Impairment

Experimental group

Description:

Participants with mild hepatic impairment (Child-Pugh Class A, score of 5 to 6, inclusive) will be administered a single dose of ipatasertib (100 mg).

Treatment:

Drug: Ipatasertib

Moderate Hepatic Impairment

Experimental group

Description:

Participants with moderate hepatic impairment (Child-Pugh Class B, score of 7 to 9, inclusive) will be administered a single dose of ipatasertib (100 mg).

Treatment:

Drug: Ipatasertib

Severe Hepatic Impairment

Experimental group

Description:

Participants with severe hepatic impairment (Child-Pugh Class C, score of 10 to 15, inclusive) will be administered a single dose of ipatasertib (100 mg).

Treatment:

Drug: Ipatasertib