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A Study to Investigate the Effect of Impaired Hepatic Function on the Pharmacokinetics of Entrectinib in Volunteers With Different Levels of Hepatic Function

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04226833
Recruitment Status : Suspended (Recruitment is currently on hold due to COVID-19 pandemic)
First Posted : January 13, 2020
Last Update Posted : May 14, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hepatic Insufficiency Drug: entrectinib Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 11, 2020
Estimated Primary Completion Date : November 5, 2020
Estimated Study Completion Date : November 5, 2020

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.
Drug: entrectinib
1x100 milligram (mg) capsule given with approximately 240 milliliter (mL) of water within 30 minutes of consumption of a standardized meal
Other Names:
  • F06 formulation
  • Rozlytrek

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.
Drug: entrectinib
1x100 milligram (mg) capsule given with approximately 240 milliliter (mL) of water within 30 minutes of consumption of a standardized meal
Other Names:
  • F06 formulation
  • Rozlytrek

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.
Drug: entrectinib
1x100 milligram (mg) capsule given with approximately 240 milliliter (mL) of water within 30 minutes of consumption of a standardized meal
Other Names:
  • F06 formulation
  • Rozlytrek

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.
Drug: entrectinib
1x100 milligram (mg) capsule given with approximately 240 milliliter (mL) of water within 30 minutes of consumption of a standardized meal
Other Names:
  • F06 formulation
  • Rozlytrek




Primary Outcome Measures :
  1. Maximum observed plasma concentration (Cmax) of entrectinib and its metabolite (M5) [ Time Frame: From Day 1 to Day 7 ]
  2. 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 ]
  3. 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 ]
  4. AUCinf of entrectinib of individual treatment groups assessed by Child-Pugh and NCI-ODWG classifications [ Time Frame: From Day 1 to Day 7 ]

Secondary Outcome Measures :
  1. Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 4 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04226833


Locations
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Czechia
Pharmaceutical Research Associates CZ, s.r.o.
Praha 7, Czechia, 170 00
Hungary
CRU Hungary Kft
Miskolc, Hungary, 3529
Slovakia
Summit Clinical Research s.r.o.; Oddelenie internej mediciny a klinickej farmakologie
Bratislava, Slovakia, 831 01
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04226833    
Other Study ID Numbers: GP41174
2019-003065-17 ( EudraCT Number )
First Posted: January 13, 2020    Key Record Dates
Last Update Posted: May 14, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hoffmann-La Roche:
Hepatic Impairment
Additional relevant MeSH terms:
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Hepatic Insufficiency
Liver Failure
Liver Diseases
Digestive System Diseases
Entrectinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action