- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04226833
A Study to Investigate the Effect of Impaired Hepatic Function on the Pharmacokinetics of Entrectinib in Volunteers With Different Levels of Hepatic Function
January 14, 2022 updated by: Hoffmann-La Roche
An Open-Label, One Treatment, Four Group, Parallel Group Study to Investigate the Effect of Impaired Hepatic Function on the Pharmacokinetics of Entrectinib in Volunteers With Different Levels of Hepatic Function
This is a non-randomized, open-label, one treatment, four group, parallel group study to investigate the effect of impaired hepatic function on the pharmacokinetics of entrectinib in participants with different levels of hepatic function.
Participants with mild, moderate or severe hepatic impairment ('Mild', 'Moderate' and 'Severe' groups), and control participants with normal hepatic function ('Normal' group) will each receive a single 100 mg dose of entrectinib after consumption of a standardized meal.
Study Overview
Detailed Description
Participants with reduced hepatic function will be assigned to a functional category based on assessments at the Screening visit.
Each individual will be categorized according to the Child Pugh system for classifying hepatic impairment and also according to the National Cancer Institute organ dysfunction working group (NCI-ODWG) system.
Recruitment will be staggered to allow review of pharmacokinetic and safety data from at least three participants in each of the Mild and Moderate groups before participants are enrolled into the Severe group.
Recruitment of the Severe group will only proceed if there is agreement between the Sponsor and the Investigator that data from this group are necessary to fulfill the objectives of the study and that dosing is not anticipated to present an unacceptable risk to those individuals.
The control group of participants with normal hepatic function will be enrolled after the full complement of participants with hepatic dysfunction has been dosed.
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
All participants:
- A body mass index (BMI) between 18.0 and 38.0 kg/m2, and weighing at least 50 kg
- Agreement to comply with measures to prevent pregnancy and restrictions on sperm donation.
Participants with normal hepatic function:
- Normal hepatic function and no history of clinically significant hepatic dysfunction.
- Healthy for age-group in the opinion of the Investigator.
Participants with hepatic impairment:
- Mild, moderate or severe hepatic dysfunction (i.e. Child-Pugh A, B or C, NCIODWG Mild, Moderate or Severe) arising from cirrhosis of the liver as the result of parenchymal liver disease.
- Stable hepatic function.
Exclusion Criteria:
- Transjugular intrahepatic portosystemic shunt or other porta-caval shunt.
- A history of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers.
- Recent history or signs of severe hepatic encephalopathy (e.g., a portal systemic encephalopathy score >2).
- Advanced ascites or ascites which require emptying and albumin supplementation.
- Hepatocellular carcinoma, acute liver disease or serum ALT or AST not consistent with stable disease.
- Recipient of a liver transplant.
- Uncontrolled hypertension.
- Clinically significant impairment of renal function.
- A history of gastrointestinal surgery or other gastrointestinal disorder that might affect absorption of medicines from the gastrointestinal tract.
- Clinically significant change in health status, or any major illness, or clinically significant acute infection or febrile illness.
- Women who are pregnant or lactating.
- Presence of any abnormal ECG finding, which is clinically significant.
- Use of moderate or potent inhibitors or inducers of cytochrome P450 3A4 enzyme.
- Participation in any other clinical study involving administration of an investigational medicinal product or use of an unapproved device.
- A positive test result for human immunodeficiency virus (HIV).
- Known history of clinically significant hypersensitivity, or severe allergic reaction, to entrectinib or related compounds or other excipients in the entrectinib formulation.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Mild
Participants with mild hepatic impairment will receive 1x100 milligram (mg) F06 (entrectinib) capsule administered orally with approximately 240 milliliter (mL) water within 30 minutes after consumption of a standardized meal.
|
1x100 milligram (mg) capsule given with approximately 240 milliliter (mL) of water within 30 minutes of consumption of a standardized meal
Other Names:
|
EXPERIMENTAL: Moderate
Participants with moderate hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
1x100 milligram (mg) capsule given with approximately 240 milliliter (mL) of water within 30 minutes of consumption of a standardized meal
Other Names:
|
EXPERIMENTAL: Severe
Participants with severe hepatic impairment will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
1x100 milligram (mg) capsule given with approximately 240 milliliter (mL) of water within 30 minutes of consumption of a standardized meal
Other Names:
|
EXPERIMENTAL: Normal
Participants with normal hepatic function will receive 1x100 mg F06 (entrectinib) capsule administered orally with approximately 240 mL water within 30 minutes after consumption of a standardized meal.
|
1x100 milligram (mg) capsule given with approximately 240 milliliter (mL) of water within 30 minutes of consumption of a standardized meal
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Maximum observed plasma concentration (Cmax) of entrectinib and its metabolite (M5)
Time Frame: From Day 1 to Day 7
|
From Day 1 to Day 7
|
Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of entrectinib and its metabolite (M5)
Time Frame: From Day 1 to Day 7
|
From Day 1 to Day 7
|
Cmax of entrectinib of individual treatment groups assessed by Child-Pugh and National Cancer Institute-organ dysfunction working group (NCI-ODWG) classifications
Time Frame: From Day 1 to Day 7
|
From Day 1 to Day 7
|
AUCinf of entrectinib of individual treatment groups assessed by Child-Pugh and NCI-ODWG classifications
Time Frame: From Day 1 to Day 7
|
From Day 1 to Day 7
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: 4 weeks
|
4 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
February 11, 2020
Primary Completion (ACTUAL)
September 27, 2021
Study Completion (ACTUAL)
September 27, 2021
Study Registration Dates
First Submitted
January 10, 2020
First Submitted That Met QC Criteria
January 10, 2020
First Posted (ACTUAL)
January 13, 2020
Study Record Updates
Last Update Posted (ACTUAL)
January 19, 2022
Last Update Submitted That Met QC Criteria
January 14, 2022
Last Verified
January 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- GP41174
- 2019-003065-17 (EUDRACT_NUMBER)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
IPD Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com).
Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx).
For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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