An Absorption, Distribution, Metabolism, Excretion (ADME) Study of [14C]Subasumstat in Adults With Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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The main aim of this study is to assess how the human body of adults with advanced or metastatic solid tumors absorbs, distributes, metabolizes and excretes subasumstat following a single 1 hour infusion of subasumstat. The study consists of two parts. In Part A, participants will receive a single infusion of C14 radiolabeled subasumstat. In Part B, participants will receive subasumstat treatment for up to 1 year.

Detailed Description
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The drug being tested in this study is called [14C]subasumstat. [14C]Subasumstat is being tested to assess mass balance and absorption, distribution, metabolism, excretion (ADME) of people who have advanced or metastatic solid tumors. The study will enroll approximately 10 patients. Participants will be enrolled to receive a single dose of [14C]subasumstat: - [14C]Subasumstat 90 mg Participants will be administered with a single dose of [14C]subasumstat 90 mg as a 1-hour intravenous (IV) infusion on Day 1 of Part A. All participants will be monitored for up to 14 days postdose. Participants will then have an option to enter Part B of the study to receive non-radiolabelled subasumstat 90 mg, IV infusion on Days 1, 4, 8, and 11 of a 21-day cycle for 3 cycles up to maximum treatment duration of 1 year. This multi-center trial will be conducted in Hungary. The overall study duration is 12 months for Part A and 24 months for Part B.

Official Title
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A Phase 1 Study to Assess Mass Balance, Pharmacokinetics, and Metabolism of [14C]Subasumstat in Patients With Advanced or Metastatic Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: [14C] Subasumstat
* Drug: Subasumstat


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants have histologically or cytologically confirmed advanced (locally regionally recurrent not amenable to curative therapy) or metastatic solid tumors with no standard therapeutic option with a proven clinical benefit, are intolerant or have refused them. Participants have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale. Participants demonstrate adequate organ function. Participants have recovered to Grade 1 or baseline from all toxicity associated with previous therapy or have the toxicity established as sequela. Key Exclusion Criteria: Participants received treatment with radioisotopes within 5 half-lives before the first dose of the study drug. Participants received radiolabelled substances, were exposed to radiation sources within 12 months of the first dose in this study, or is likely to receive radiation exposure or radioisotopes within 12 months of the first dose in this study such that participation in this study would increase their total exposure beyond the recommended safe levels. Participants received extended field radiotherapy ≤4 weeks before the start of treatment. Participants have uncontrolled brain metastasis. Participants with treated brain metastases are allowed provided they are radiologically stable, without evidence of progression for at least 4 weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days before first dose of study treatment. Participants had a second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the patient is not on active anticancer therapies. Major surgery ≤14 days from the first dose of study drug and not recovered fully from any complications from surgery. Baseline prolongation of the QT interval when corrected using Fridericia's formula (QTcF). Receiving or requires the continued use of medications that are known to be strong or moderate inhibitors and inducers of cytochrome P450 (CYP) 3A4/5 and strong P-glycoprotein (Pgp) inhibitors. Has active noninfectious pneumonitis or interstitial lung disease that required steroids. History of allogeneic tissue or solid organ transplant. Participants have active bacterial infection requiring systemic therapy <14 days before the start of treatment. Participants have an active HIV or any other relevant congenital or acquired immunodeficiency. Active hepatitis B, or hepatitis C infection. Any of the following uncontrolled heart diseases: congestive heart failure New York Heart Association Grade III or IV, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled hypertension despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias >Grade 2, pulmonary embolism or symptomatic cerebrovascular events, or any other serious cardiac condition (eg, pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [14C] Subasumstat 90 mg<br>Participants will receive a single dose of [14C] Subasumstat 90 mg, IV infusion on Day 1 in Part A of the study. Following Part A, participants will have an option to receive subasumstat 90 mg, IV infusion on Days 1, 4, 8, and 11 of a 21 day cycle for 3 cycles followed by weekly maintenance dosing in Part B of the study up to maximum treatment duration of 1 year. | Drug: [14C] Subasumstat<br>* [14C] Subasumstat IV infusion.<br>* Other names: TAK-981;Drug: Subasumstat<br>* Subasumstat IV infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Percentage of Urinary Recovery | Cumulative amount of [14C]-radioactivity excreted in urine up to the last sampling interval. | Up to 14 days postdose | 
| Cumulative Percentage of Fecal Recovery | Cumulative amount of [14C]-radioactivity excreted in feces up to the last sampling interval. | Up to 14 days postdose | 
| Cumulative Percentage of Combined Recovery | Cumulative amount of [14C]-radioactivity excreted in urine, and feces up to the last sampling interval. | Up to 14 days postdose | 
| Percentage Of Recovered Total Radioactivity (TRA) In Urine And Feces | Percentage of recovered TRA in urine and feces for each interval over the entire period of collection will be reported. | Up to 14 days postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax: Maximum Observed Plasma Concentration for Subasumstat and TRA in Plasma and Whole Blood |  | Predose on Day 1 and at multiple time points postdose up to Day 14 | 
| Tmax: Time of First Occurrence of Cmax for Subasumstat and TRA in Plasma and Whole Blood |  | Predose on Day 1 and at multiple time points postdose up to Day 14 | 
| AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Subasumstat and TRA in Plasma and Whole Blood |  | Predose on Day 1 and at multiple time points postdose up to Day 14 | 
| Terminal Disposition Phase Half-life (T1/2z) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data |  | Predose on Day 1 and at multiple time points postdose up to Day 14 | 
| Clearance (CL) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data |  | Predose on Day 1 and at multiple time postdose points up to Day 14 | 
| Volume of Distribution at Steady-state (Vss) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data |  | Predose on Day 1 and at multiple time points postdose up to Day 14 | 
| AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data |  | Predose on Day 1 and at multiple time points postdose up to Day 14 | 
| Cumulative Amount of Unchanged Subasumstat and TRA Excreted into the Urine (Aeurine) |  | Predose on Day 1 and at multiple time points postdose up to Day 14 | 
| Renal Clearance (CLR) for Subasumstat and TRA in Urine |  | Predose on Day 1 and at multiple time points postdose up to Day 14 | 
| Number of Participants With One or More Adverse Events (AEs) | 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. | From the start of study drug administration through 30 days after the last dose of study drug (up to approximately 1 year) | 
| Number of Participants With One or More Serious Adverse Events (SAEs) | An 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. A SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. | From the start of study drug administration through 30 days after the last dose of study drug (up to approximately 1 year) | 
| Number of Participants With Abnormal Electrocardiogram Findings | Abnormal laboratory values are those outside of normal range as assessed by the investigator. | From the start of study drug administration through the last dose of study drug (up to approximately 1 year) | 
| Number of Participants With Abnormal Laboratory Values | Laboratory findings will include serum chemistry, hematology and urinalysis. Abnormal laboratory values are those outside of normal range as assessed by the investigator. | From the start of study drug administration through the last dose of study drug (up to approximately 1 year) | 
| Relative Percentage of Circulatory Metabolites in Plasma |  | Predose on Day 1 and at multiple time points postdose up to Day 14 | 
| Relative Percentage Excretory Metabolites in Urine |  | Predose on Day 1 and at multiple time points postdose up to Day 14 | 
| Relative Percentage Excretory Metabolites in Feces |  | Predose on Day 1 and at multiple time points postdose up to Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy