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

Phase 1TerminatedNCT05976334

Takeda3 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumors

Interventions

[14C] SubasumstatDRUG

\[14C\] Subasumstat IV infusion.

SubasumstatDRUG

Subasumstat IV infusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. 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. 2. Participants have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale. 3. Participants demonstrate adequate organ function. 4. 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: 1. Participants received treatment with radioisotopes within 5 half-lives before the first dose of the study drug. 2. 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. 3. Participants received extended field radiotherapy ≤4 weeks before the start of treatment. 4. 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. 5. 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. 6. Major surgery ≤14 days from the first dose of study drug and not recovered fully from any complications from surgery. 7. Baseline prolongation of the QT interval when corrected using Fridericia's formula (QTcF). 8. 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. 9. Has active noninfectious pneumonitis or interstitial lung disease that required steroids. 10. History of allogeneic tissue or solid organ transplant. 11. Participants have active bacterial infection requiring systemic therapy \<14 days before the start of treatment. 12. Participants have an active HIV or any other relevant congenital or acquired immunodeficiency. 13. Active hepatitis B, or hepatitis C infection. 14. 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.

Locations (2)

Central Hospital of Northern Pest - Military Hospital

Budapest, Hungary

Pharmaceutical Research Associates Magyarorszag

Budapest, Hungary

Outcomes

Primary Outcomes

Cumulative Percentage of Urinary Recovery

Cumulative percentage of \[14C\]-radioactivity excreted in urine up to the last sampling interval.

Time frame: Up to 14 days post-dose

Cumulative Percentage of Fecal Recovery

Cumulative percentage of \[14C\]-radioactivity excreted in feces up to the last sampling interval.

Time frame: Up to 14 days post-dose

Cumulative Percentage of Combined Recovery

Cumulative percentage of \[14C\]-radioactivity excreted in urine, and feces up to the last sampling interval.

Time frame: Up to 14 days post-dose

Percentage Of Recovered Total Radioactivity (TRA) In Urine

Percentage of recovered TRA in urine for each interval over the entire period of collection were reported.

Time frame: Post-dose Day 1: 0-6 hours (hr), 6-12 hr, Day 2: 12-24 hr, Day 3: 24-48 hr, Day 4: 48-72, Day 5: 72-96 hr, Day 6: 96-120 hr, Day 7: 120-144 hr, Day 8: 144-168 hr, Day 9: 168-192 hr, Day 10: 192-216 hr, Day 11: 216-240 hr, Day 12: 240-264 hr

Percentage Of Recovered Total Radioactivity (TRA) In Feces

Percentage of recovered TRA in feces for each interval over the entire period of collection were reported.

Time frame: Post-dose Day 1: 0-6 hours hr, 6-12 hr, Day 2: 12-24 hr, Day 3: 24-48 hr, Day 4: 48-72 hr, Day 5: 72-96 hr, Day 6: 96-120 hr, Day 7: 120-144 hr, Day 8: 144-168 hr, Day 9: 168-192 hr, Day 10: 192-216 hr, Day 11: 216-240 hr

Secondary Outcomes

Cmax: Maximum Observed Plasma Concentration for Subasumstat and TRA in Plasma and Whole Blood

Time frame: Pre-dose and Post-dose Day 1: 0.5 hr,1 hr,2 hr,4 hr,8 hr; Day 2: 24 hr, Day 3: 48 hr; Day 4:72 hrs; Day 5: 96 hrs; Day 6: 120 hr, Day 7: 144 hr; Day 8: 168 hr; Day 9: 192 hr,;Day 10: 216 hr; Day 11: 240 hr; Day 12: 264 hr; Day 13: 288 hr; Day 14: 312 hr

Data from ClinicalTrials.gov

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