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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

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ClinicalTrials.gov Identifier: NCT04226833
Recruitment Status : Active, not recruiting
First Posted : January 13, 2020
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE January 10, 2020
First Posted Date  ICMJE January 13, 2020
Last Update Posted Date September 16, 2021
Actual Study Start Date  ICMJE February 11, 2020
Estimated Primary Completion Date September 16, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2020)
  • Maximum observed plasma concentration (Cmax) of entrectinib and its metabolite (M5) [ Time Frame: 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 ]
  • 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 ]
  • AUCinf of entrectinib of individual treatment groups assessed by Child-Pugh and NCI-ODWG classifications [ Time Frame: From Day 1 to Day 7 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2020)
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 4 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Investigate the Effect of Impaired Hepatic Function on the Pharmacokinetics of Entrectinib in Volunteers With Different Levels of Hepatic Function
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatic Insufficiency
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: entrectinib
  • 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.
    Intervention: Drug: entrectinib
  • 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.
    Intervention: Drug: entrectinib
  • 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.
    Intervention: Drug: entrectinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 10, 2020)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 16, 2021
Estimated Primary Completion Date September 16, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   Hungary,   Slovakia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04226833
Other Study ID Numbers  ICMJE GP41174
2019-003065-17 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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).
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP