Clinical trial NCT03341884: A Study of Ipatasertib in Participants With Mild, Moderate or Severe Hepatic Impairment Compared to Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Insufficiency
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2017-11-14
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve (AUC) from 0 to Infinity (AUC0-inf) of Ipatasertib
timeFrame: up to Day 15
measure: Maximum Observed Plasma Concentration (Cmax) of Ipatasertib
timeFrame: up to Day 15
Secondary outcomes:
measure: Percentage of Participants with Treatment-Emergent Adverse Events (AE)
timeFrame: up to Day 15
measure: Time to Reach Maximum Observed Concentration (tmax) of Ipatasertib
timeFrame: up to Day 15
measure: AUC from 0 to last measurable concentration (AUC0-t)
timeFrame: up to Day 15
measure: Half-life (t1/2) of Ipatasertib
timeFrame: up to Day 15
measure: Apparent Plasma Clearance (CL/F) of Ipatasertib
timeFrame: Up to Day 15
measure: Apparent Volume of Distribution (V/F) of Ipatasertib
timeFrame: up to Day 15
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami, Inc.
state: Florida
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
city: San Antonio
country: United States
facility: American Research Corporation Inc.
state: Texas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: