Back to resultsA Study of Ipatasertib in Participants With Mild, Moderate or Severe Hepatic Impairment Compared to Healthy Participants
Primary Purpose
Hepatic Insufficiency
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ipatasertib
Sponsored by
About this trial
This is an interventional treatment trial for Hepatic Insufficiency
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
Sites / Locations
- Clinical Pharmacology of Miami, Inc.
- New Orleans Center for Clinical Research
- American Research Corporation Inc.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Normal Hepatic Function
Mild Hepatic Impairment
Moderate Hepatic Impairment
Severe Hepatic Impairment
Arm Description
Participants with normal hepatic function will be administered a single oral dose of ipatasertib (100 mg).
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).
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).
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).
Outcomes
Primary Outcome Measures
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.
Maximum Observed Plasma Concentration (Cmax) of Ipatasertib
Maximum observed concentration of ipatasertib as determined by measuring drug concentration in blood samples over time.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Apparent Volume of Distribution (V/F) of Ipatasertib
Apparent volume of distribution (V/F) during the terminal phase of ipatasertib.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03341884
Brief Title
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
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
November 9, 2017 (Actual)
Primary Completion Date
June 26, 2018 (Actual)
Study Completion Date
June 26, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Insufficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Normal Hepatic Function
Arm Type
Experimental
Arm Description
Participants with normal hepatic function will be administered a single oral dose of ipatasertib (100 mg).
Arm Title
Mild Hepatic Impairment
Arm Type
Experimental
Arm 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).
Arm Title
Moderate Hepatic Impairment
Arm Type
Experimental
Arm 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).
Arm Title
Severe Hepatic Impairment
Arm Type
Experimental
Arm 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).
Intervention Type
Drug
Intervention Name(s)
Ipatasertib
Other Intervention Name(s)
GDC-0068
Intervention Description
A single oral dose of 100 mg ipatasertib will be administered.
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration-Time Curve (AUC) from 0 to Infinity (AUC0-inf) of Ipatasertib
Description
AUC0-inf is defined as AUC extrapolated from Hour 0 to infinity of ipatasertib in the plasma.
Time Frame
up to Day 15
Title
Maximum Observed Plasma Concentration (Cmax) of Ipatasertib
Description
Maximum observed concentration of ipatasertib as determined by measuring drug concentration in blood samples over time.
Time Frame
up to Day 15
Secondary Outcome Measure Information:
Title
Percentage of Participants with Treatment-Emergent Adverse Events (AE)
Description
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.
Time Frame
up to Day 15
Title
Time to Reach Maximum Observed Concentration (tmax) of Ipatasertib
Description
Time from dose administration to observed maximum serum concentration for ipatasertib as determined by measuring drug concentration in blood samples over time.
Time Frame
up to Day 15
Title
AUC from 0 to last measurable concentration (AUC0-t)
Description
Area under the plasma concentration-time curve from Hour 0 to the last measurable concentration of ipatasertib.
Time Frame
up to Day 15
Title
Half-life (t1/2) of Ipatasertib
Description
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.
Time Frame
up to Day 15
Title
Apparent Plasma Clearance (CL/F) of Ipatasertib
Description
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.
Time Frame
Up to Day 15
Title
Apparent Volume of Distribution (V/F) of Ipatasertib
Description
Apparent volume of distribution (V/F) during the terminal phase of ipatasertib.
Time Frame
up to Day 15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Pharmacology of Miami, Inc.
City
Miami
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Facility Name
New Orleans Center for Clinical Research
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
American Research Corporation Inc.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of Ipatasertib in Participants With Mild, Moderate or Severe Hepatic Impairment Compared to Healthy Participants
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