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

NCT04056455 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: TAK-788-1007U1111-1236-7343
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Renal Impairment; Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (19)

• 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

• AUCinf: 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

• AUCinf,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

• Combined Molar Cmax,u: Combined Molar Unbound 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

• Combined Molar AUClast,u: Combined Molar Unbound AUClast for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)

  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)

  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 Phase 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

• CumAe: Cumulative Amount of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) Excreted in the Urine

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose

• Cumfe: Cumulative Fraction of Mobocertinib Excreted in the Urine

  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)

  Day 1 pre-dose and at multiple time points (up to 120 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)

  From first dose of study drug up to end of study (EOS) (up to 40 days)

Study Arms (2)

Severe Renal Impairment: Mobocertinib 80 mg

EXPERIMENTAL

Participants with severe renal impairment received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.

Drug: Mobocertinib

Normal Renal Function: Mobocertinib 80 mg

EXPERIMENTAL

Participants with normal renal function received a single dose of mobocertinib 80 mg, capsule, orally, on Day 1.

Drug: Mobocertinib

Interventions

Mobocertinib DRUG

Mobocertinib capsule.

Also known as: TAK-788, AP32788

Normal Renal Function: Mobocertinib 80 mg; Severe Renal Impairment: Mobocertinib 80 mg

Eligibility Criteria

• Age: 18 Years - 81 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 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.
• 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.
• 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.
• 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.
• 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 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.
• 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.
• 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.

You may not qualify if:

• Positive results at screening for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
• Positive test result for coronavirus disease 2019 (COVID-19) testing at screening or check-in.
• Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening.
• Seated blood pressure is less than 90/40 millimeters of mercury (mmHg) or greater than 180/100 mmHg at screening.
• 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
• RI participants: QTcF interval is \>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) as indicated in (Prohibitions and Concomitant Medication) 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 significant blood loss within 56 days prior to dosing.
• Plasma donation within 7 days prior to dosing.

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

Related Links

• Related Info

MeSH Terms

Conditions

Renal Insufficiency

Interventions

mobocertinib

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Millennium Pharmaceuticals, Inc.

  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: March 4, 2020
• Primary Completion: April 20, 2022
• Study Completion: April 20, 2022
• Last Updated: January 8, 2024
• Results First Posted: January 8, 2024

Record last verified: 2023-03

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)