Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Pharmacokinetic (PK) Study of Oral Mobocertinib in Participants With Severe Renal Impairment (RI) and Normal Renal 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04056455
Recruitment Status : Recruiting
First Posted : August 14, 2019
Last Update Posted : October 14, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
The purpose of this study is to characterize the single-dose plasma and urine PK of mobocertinib and its active metabolites (AP32960 and AP32914) in participants with severe RI compared to matched-healthy participants with normal renal function.

Condition or disease Intervention/treatment Phase
Renal Impairment Healthy Volunteers Drug: Mobocertinib Phase 1

Detailed Description:

29-Apr-2020 Enrollment of new patients into this study was paused due to the COVID-19 situation. The duration of this pause was dependent on the leveling and control of the COVID-19 pandemic.

The drug being tested in this study is called mobocertinib. This study is to assess the PK of mobocertinib and its active metabolites (including but not limited to AP32960 and AP32914) in participants with severe RI compared to matched-healthy participants with normal renal function.

The study will enroll approximately 16 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase 1 Pharmacokinetic Study of Oral Mobocertinib in Subjects With Severe Renal Impairment and Normal Renal Function
Actual Study Start Date : March 10, 2020
Estimated Primary Completion Date : April 22, 2021
Estimated Study Completion Date : April 22, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Tests

Arm Intervention/treatment
Experimental: Severe RI: Mobocertinib 80 mg
Mobocertinib milligram (mg), capsule, orally, a single dose on Day 1.
Drug: Mobocertinib
Mobocertinib capsule.
Other Names:
  • TAK-788
  • AP32788

Experimental: Normal Renal Function: Mobocertinib 80 mg
Mobocertinib 80 mg, capsule, orally, a single dose on Day 1.
Drug: Mobocertinib
Mobocertinib capsule.
Other Names:
  • TAK-788
  • AP32788




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. λz: Terminal Disposition 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 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. Aet: Amount of Drug Excreted in Urine From Time 0 to time t for 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 ]
  18. fe,t: Fraction of Administered Dose Excreted in Urine From Time 0 to Time t for 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 ]
  19. CLR: Renal Clearance for 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to 30 days after the last of study drug (Day 31) ]


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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 less than or equal to (<=) 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 1.73 square meter (mL/min/1.73 m^2) based on the Modification of Diet in Renal Disease (MDRD) equation at screening.

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 <30 mL/min/1.73 m^2 not on dialysis based on the MDRD equation at screening.
  5. Has a diagnosis of chronic (>6 months), stable (no significant changes in renal function [<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.

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): NCT04056455


Contacts
Layout table for location contacts
Contact: Takeda Study Registration Call Center +1-877-825-3327 medinfoUS@takeda.com

Locations
Layout table for location information
United States, Florida
Clinical Pharmacology of Miami Recruiting
Hialeah, Florida, United States, 33014
Orlando Clinical Research Center Recruiting
Orlando, Florida, United States, 32809
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Layout table for investigator information
Study Director: Medical Director Millennium Pharmaceuticals, Inc.
Layout table for additonal information
Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04056455    
Other Study ID Numbers: TAK-788-1007
U1111-1236-7343 ( Registry Identifier: WHO )
First Posted: August 14, 2019    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: https://vivli.org/ourmember/takeda/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug Therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Renal Insufficiency
Kidney Diseases
Urologic Diseases