A Study of Mobocertinib Capsules in People With Severe Kidney Problems and People With Healthy Kidneys

March 28, 2023 updated by: Millennium Pharmaceuticals, Inc.

A Phase 1 Pharmacokinetic Study of Oral Mobocertinib in Subjects With Severe Renal Impairment and Normal Renal Function

It is hoped that mobocertinib will eventually help people with cancer with severely reduced kidney function. The main aim of this study is to learn about the levels of mobocertinib in the blood and urine of participants with severely reduced kidney function and participants with healthy kidneys. These participants do not have cancer. The information from this study will be used to work out the best dose of mobocertinib for people with cancer with severely reduced kidney function in the future.

At the first visit, the study doctor will check who can take part. Participants who can take part will be placed into 1 of 2 treatment groups. Participants with severely reduced kidney function will be in 1 group. Participants with healthy kidneys will be in the other group. Participants in both groups will receive the same treatment and the group results will be compared.

Participants from both groups will take 1 capsule of mobocertinib. They will stay in the clinic for 10 days so the study doctors can check the amount of mobocertinib in the blood and urine of these participants over time. The study doctors will also check if the participants have any side effects from this treatment.

The clinic will call the participants 30 days after they took mobocertinib to check if they have any more side effects from their treatment.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

The drug being tested in this study is called mobocertinib. This study is to assess the pharmacokinetic (PK) of mobocertinib and its active metabolites (AP32960 and AP32914) in participants with severe RI compared to matched-healthy participants with normal renal function.

The study will enroll approximately 24 participants. Participants will be assigned to 1 of the following 2 treatment groups:

  • Severe RI: Mobocertinib 80 mg
  • Normal Renal Function: Mobocertinib 80 mg

Healthy participants with normal renal function will be recruited to match severe RI by age (mean plus or minus [+-] 10 years), gender (+-2 participants per gender), and body mass index (BMI), (mean +- 10 percent [%]). All participants will be asked to take single dose of mobocertinib on Day 1.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is 51 days. Participants will be contacted by telephone 30 days after the last dose of study drug for a follow-up assessment.

Study Type

Interventional

Enrollment (Actual)

26

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.

Study Locations

    • Florida
      • Hialeah, Florida, United States, 33014
        • Clinical Pharmacology of Miami
      • Orlando, Florida, United States, 32809
        • Orlando Clinical Research Center

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

16 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Inclusion Criteria for Healthy Participants:

  1. 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.
  2. 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 RI participants by BMI (mean +- 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.
  3. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or 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.
  4. Baseline estimated glomerular filtration rate (eGFR) >=90 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) based on the Modification of Diet in Renal Disease (MDRD) equation at screening divided by standard body surface area (BSA) value of 1.73 m^2. For participants with non-standard BSA, the eGFR value calculated by MDRD formula will be multiplied by the individual's BSA calculated using appropriate formula and divided by 1.73 m^2.

Inclusion Criteria for Participants with RI:

  1. 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 dose of mobocertinib and throughout the period of PK sample collection.
  2. 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.
  3. Aside from RI, 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.
  4. Baseline eGFR 15-29 milliliter (mL) not on dialysis based on the MDRD equation at screening divided by standard BSA value of 1.73 m^2. For participants with non-standard BSA, the eGFR value calculated by MDRD formula will be multiplied by the individual's BSA calculated using appropriate formula and divided by 1.73 m^2.
  5. Has a diagnosis of chronic (greater than [>] 6 months), stable (no significant changes in renal function [less than [<] 30%] in the 30 days preceding screening; no acute episodes of illness within the previous 2 months due to deterioration in renal function) renal insufficiency. Participants with RI may have related medical conditions consistent with their disease (example, mild diabetes) that are stable for at least 3 months prior to screening, in the opinion of the Investigator or designee.

Exclusion Criteria

  1. Positive results at screening for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
  2. Positive test result for coronavirus disease 2019 (COVID-19) testing at screening or check-in.
  3. Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening.
  4. Seated blood pressure is less than 90/40 millimeters of mercury (mmHg) or greater than 180/100 mmHg at screening.
  5. Healthy participants: QT interval with Fridericia's correction (QTcF) interval is >=450 millisecond (msec) in males or >=470 msec in females or has ECG findings deemed abnormal with clinical significance by the Investigator or designee at screening
  6. RI participants: QTcF interval is >500 msec or has ECG findings deemed abnormal with clinical significance by the Investigator or designee at screening.
  7. 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) as indicated in (Prohibitions and Concomitant Medication) for the prohibited time period.
  8. 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.
  9. Donation of blood or significant blood loss within 56 days prior to dosing.
  10. Plasma donation within 7 days prior to dosing.

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: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Severe Renal Impairment: Mobocertinib 80 mg
Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
Mobocertinib capsule.
Other Names:
  • AP32788
  • TAK-788
Experimental: Normal Renal Function: Mobocertinib 80 mg
Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.
Mobocertinib capsule.
Other Names:
  • AP32788
  • TAK-788

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CL/F: Apparent Clearance After Extravascular Administration for Mobocertinib
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
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
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
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
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
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
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
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)
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
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)
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
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)
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
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)
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
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)
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
AUCinf,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Combined Molar Cmax,u: Combined Molar Unbound Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Combined Molar AUClast,u: Combined Molar Unbound AUClast for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Combined Molar AUCinf,u: Combined Molar Unbound AUCinf for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
λz: Terminal Elimination Phase Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time Frame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
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
CumAe: Cumulative Amount of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) Excreted in the Urine
Time Frame: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
Cumfe: Cumulative Fraction of Mobocertinib Excreted in the Urine
Time Frame: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time Frame: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
Time Frame: Day 1 at multiple time points (up to 24 hours) post-dose
Day 1 at multiple time points (up to 24 hours) post-dose
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time Frame: From first dose of study drug up to end of study (EOS) (up to 40 days)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A Treatment-emergent Adverse Event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
From first dose of study drug up to end of study (EOS) (up to 40 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Study Director, Millennium Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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)

March 4, 2020

Primary Completion (Actual)

April 20, 2022

Study Completion (Actual)

April 20, 2022

Study Registration Dates

First Submitted

August 13, 2019

First Submitted That Met QC Criteria

August 13, 2019

First Posted (Actual)

August 14, 2019

Study Record Updates

Last Update Posted (Estimated)

January 8, 2024

Last Update Submitted That Met QC Criteria

March 28, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • TAK-788-1007
  • U1111-1236-7343 (Registry Identifier: WHO)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

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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