Clinical trial NCT04056455: A Study of Mobocertinib Capsules in People With Severe Kidney Problems and People With Healthy Kidneys
Official title: A Phase 1 Pharmacokinetic Study of Oral Mobocertinib in Subjects With Severe Renal Impairment and Normal Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-08-14
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 81
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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.

Eligibility 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 \<=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.

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: Cmax,u: Maximum Observed Unbound Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: AUCinf,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: 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)
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: 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)
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: Combined Molar Cmax,u: Combined Molar Unbound Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: Combined Molar AUClast,u: Combined Molar Unbound AUClast for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: Combined Molar AUCinf,u: Combined Molar Unbound AUCinf for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: t1/2z: Terminal Disposition Phase Half-life for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: λz: Terminal Elimination Phase Rate Constant for Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: CL/F: Apparent Clearance After Extravascular Administration for Mobocertinib
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for Mobocertinib
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: Vz,u/F: Apparent Volume of Distribution for Unbound Drug During the Terminal Disposition Phase After Extravascular Administration for Mobocertinib
timeFrame: Day 1 pre-dose and at multiple time points (up to 216 hours) post-dose
measure: CumAe: Cumulative Amount of Mobocertinib and Its Active Metabolites (AP32960 and AP32914) Excreted in the Urine
timeFrame: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
measure: Cumfe: Cumulative Fraction of Mobocertinib Excreted in the Urine
timeFrame: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
measure: CLR: Renal Clearance of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
timeFrame: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
Secondary outcomes:
measure: Plasma Protein Binding of Mobocertinib and Its Active Metabolites (AP32960 and AP32914)
timeFrame: Day 1 at multiple time points (up to 24 hours) post-dose
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to end of study (EOS) (up to 40 days)
Other outcomes:
Locations:
city: Hialeah
country: United States
facility: Clinical Pharmacology of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Study Director
role: STUDY_DIRECTOR
References: