A Study to Evaluate Pharmacokinetics (PK) and Safety of Oral Mobocertinib in Participants With Moderate or Severe Hepatic Impairment (HI) and Normal Hepatic Function

NCT04056468 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: TAK-788-1008U1111-1236-7377
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to characterize the single-dose plasma PK of mobocertinib and its active metabolites (AP32960 and AP32914) in participants with moderate and/or severe HI compared to matched-healthy participants with normal hepatic function.

Conditions

Hepatic Impairment; Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (13)

• Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

• Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

• AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

• AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

• AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

• AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

• t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

• λz: Terminal Elimination Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)

  Terminal elimination rate constant (λz) is a mathematical estimate calculated using log-linear regression of the terminal portions of a plasma concentration against time curve.

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

• CL/F: Apparent Clearance After Extravascular Administration for Mobocertinib

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

• CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for Mobocertinib

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

• Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

• Vz,u/F: Apparent Volume of Distribution for Unbound Drug During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib

  Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose

Secondary Outcomes (2)

• Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)

  Day 1 at multiple time points (up to 24 hours) post-dose

• Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

  Baseline up to 30 days after last dose of study drug (up to Day 32)

Study Arms (3)

Moderate HI (Child-Pugh B): Mobocertinib 40 mg

EXPERIMENTAL

Mobocertinib 40 milligram (mg), capsule, orally, a single dose on Day 1.

Drug: Mobocertinib

Severe HI (Child-Pugh C): Mobocertinib 40 mg

EXPERIMENTAL

Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.

Drug: Mobocertinib

Normal Hepatic Function: Mobocertinib 40 mg

EXPERIMENTAL

Mobocertinib 40 mg, capsule, orally, a single dose on Day 1.

Drug: Mobocertinib

Interventions

Mobocertinib DRUG

Mobocertinib capsule.

Also known as: AP32788, TAK-788

Moderate HI (Child-Pugh B): Mobocertinib 40 mg; Normal Hepatic Function: Mobocertinib 40 mg; Severe HI (Child-Pugh C): Mobocertinib 40 mg

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Continuous non-smoker or moderate smoker (less than or equal to (\<=) 10 cigarettes/day or the equivalent) before screening. Participant must agree to consume no more than 5 cigarettes or equivalent/day from the 7 days prior to mobocertinib dosing and throughout the period of PK sample collection.
• Body mass index (BMI) greater than or equal to (\>=) 18.0 and \<=39.0 kilogram per square meter (kg/m\^2), at screening. Participants will be matched to hepatic impaired participants by BMI (mean plus minus \[+-\] 10%) at screening. At least 50% of the participants will be required to be of BMI \>=18.0 and \<=35.0 kg/m\^2, at screening.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or electrocardiograms (ECGs), as deemed by the Investigator or designee. Has liver function tests including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin within the upper limit of normal at screening and at check-in.
• Creatinine clearance (estimated glomerular filtration rate \[eGFR\]) \>=60 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) at screening.
• Continuous non-smoker or moderate smoker (\<=10 cigarettes/day or the equivalent) before screening. Participant must agree to consume no more than 5 cigarettes or equivalent/day from the 7 days prior to mobocertinib dosing and throughout the period of pharmacokinetic(s) (PK) sample collection.
• BMI \>=18.0 and \<=39.0 kg/m\^2, at screening. At least 50% of the participants will be required to be of BMI \>=18.0 and \<=35.0 kg/m\^2, at screening.
• Aside from HI, be sufficiently healthy for study participation based upon medical history, physical examination, vital signs, ECGs, and screening clinical laboratory profiles, as deemed by the Investigator or designee.
• Creatinine clearance (eGFR) \>=60 mL/min/1.73 m\^2 at screening.
• Chronic HI for at least 3 months before screening, and the HI must be stable, that is, no significant changes in hepatic function in the 30 days preceding screening (or since the last visit if within 6 months before screening) and treatment with stable doses of medication. Has a score on the Child-Pugh Class at screening as follows:
• Moderate HI arm, Child-Pugh Class B: \>=7 and \<=9.
• Severe HI arm, Child-Pugh Class C: \>=10 and \<=15.

You may not qualify if:

• Positive results for COVID-19 at screening or check in.
• Seated blood pressure is less than 90/40 millimeters of Mercury (mmHg) or greater than 150/95 mmHg at screening.
• Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening.
• Healthy participants: QTcF interval is \>=450 msec in males or \>=470 msec in females; Moderate or Severe HI participants: QTcF interval is greater than (\>) 500 msec OR has ECG findings deemed abnormal with clinical significance by the Investigator or designee at screening.
• Unable to refrain from or anticipates the use of any medication or substance (including prescription or over-the-counter, vitamin supplements, natural or herbal supplements) for the prohibited time period.
• Been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to dosing and throughout the study.
• Donation of blood or had significant blood loss within 56 days prior to dosing.
• Plasma donation within 7 days prior to dosing.
• Healthy participants: Positive result at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV); Moderate or Severe HI participants: Positive result at screening for HIV, HBsAg positive participants are allowed to enroll if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is below 1000 copies/milliliter (mL) in the plasma. Participants who are positive for hepatitis C virus antibodies (HCVAb) can be enrolled but must not have detectable HCV ribonucleic acid (RNA) in the plasma.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (2)

Clinical Pharmacology of Miami

Hialeah, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

MeSH Terms

Interventions

mobocertinib

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2019
• First Posted: August 14, 2019
• Study Start: October 9, 2020
• Primary Completion: February 5, 2022
• Study Completion: February 26, 2022
• Last Updated: November 3, 2023
• Results First Posted: November 3, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (2)