Solid Tumors
Conditions
Keywords
Drug Therapy
Brief summary
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
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.
Interventions
DRUGSubasumstat
Subasumstat IV infusion.
DRUG[14C] Subasumstat
\[14C\] Subasumstat IV infusion.
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Percentage of Urinary Recovery | Up to 14 days post-dose | Cumulative percentage of \[14C\]-radioactivity excreted in urine up to the last sampling interval. |
| Cumulative Percentage of Fecal Recovery | Up to 14 days post-dose | Cumulative percentage of \[14C\]-radioactivity excreted in feces up to the last sampling interval. |
| Cumulative Percentage of Combined Recovery | Up to 14 days post-dose | Cumulative percentage of \[14C\]-radioactivity excreted in urine, and feces up to the last sampling interval. |
| Percentage Of Recovered Total Radioactivity (TRA) In Urine | 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 TRA in urine for each interval over the entire period of collection were reported. |
| Percentage Of Recovered Total Radioactivity (TRA) In Feces | 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 | Percentage of recovered TRA in feces for each interval over the entire period of collection were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Volume of Distribution at Steady-state (Vss) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data | 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 | — |
| 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 | 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 | — |
| Cumulative Amount of Unchanged Subasumstat Excreted Into the Urine (Aeurine) | Pre-dose and post-dose at 0-6 hours (hr) and 6-12 hr on Day 1, 12-24 hr on Day 2, 24-48 hr on Day 3, 48-72 hr on Day 4, 72-96 hr on Day 5 up to Day 14 | Cumulative amount of unchanged subasumstat was determined as percentage (%) of dose of subasumstat. |
| Renal Clearance (CLR) for Subasumstat in Urine | Pre-dose and post-dose at 0-6 hours (hr) and 6-12 hr on Day 1, 12-24 hr on Day 2, 24-48 hr on Day 3, 48-72 hr on Day 4, 72-96 hr on Day 5 up to Day 14 | — |
| Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) | Up to approximately 8 months | 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. A TEAE was defined as an AE that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. |
| Cmax: Maximum Observed Plasma Concentration for Subasumstat and TRA in Plasma and Whole Blood | 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 | — |
| Number of Participants With Abnormal Electrocardiogram Findings | Up to approximately 8 months | Abnormal laboratory values are those outside of normal range as assessed by the investigator. |
| Number of Participants With Abnormal Laboratory Values | Up to approximately 8 months | Laboratory findings will include serum chemistry, hematology and urinalysis. Abnormal laboratory values are those outside of normal range as assessed by the investigator. |
| Relative Percentage of Circulatory Metabolites in Plasma | 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 and Day 8: 168 hr | — |
| Relative Percentage Excretory Metabolites in Urine | 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 and Day 8: 168 hr | — |
| Relative Percentage of Excretory Metabolites in Feces | 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 and Day 8: 168 hr | M1, M9 and M10 reported as categories were the names for the metabolites. |
| Number of Participants With One or More Serious Adverse Events (SAEs) | Up to approximately 8 months | 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. An 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. |
| Tmax: Time of First Occurrence of Cmax for Subasumstat and TRA in Plasma and Whole Blood | 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 | — |
| 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 | 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 | — |
| Terminal Disposition Phase Half-life (T1/2z) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data | 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 | — |
| Clearance (CL) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data | 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 | — |
Countries
Hungary
Participant flow
Recruitment details
3 participants took part in the study at 1 investigative site in Hungary from 14 November 2023 to 16 July 2024.
Pre-assignment details
Participants with advanced or metastatic solid tumors were enrolled in this study to receive \[14C\] subasumstat in Part A and subasumstat in Part B of this study.
Participants by arm
| Arm | Count |
|---|---|
| Part A: [14C] Subasumstat Participants received a single dose of \[14C\] subasumstat 90 mg, IV infusion on Day 1 in Part A of the study. | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part B | Death | 0 | 1 |
| Part B | Reason Not Specified | 0 | 1 |
| Part B | Study Terminated by Sponsor | 0 | 1 |
Baseline characteristics
| Characteristic | Part A: [14C] Subasumstat |
|---|---|
| Age, Continuous | 53.0 years STANDARD_DEVIATION 12.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 1 / 2 |
| other Total, other adverse events | 3 / 3 | 2 / 2 |
| serious Total, serious adverse events | 0 / 3 | 1 / 2 |
Outcome results
Primary
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
Population: SAS comprised of participants who had received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: [14C] Subasumstat | Cumulative Percentage of Combined Recovery | 85.27 percentage | Geometric Coefficient of Variation 10.8 |
Primary
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
Population: SAS comprised of participants who had received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: [14C] Subasumstat | Cumulative Percentage of Fecal Recovery | 75.76 percentage | Geometric Coefficient of Variation 14.6 |
Primary
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
Population: SAS comprised of participants who had received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: [14C] Subasumstat | Cumulative Percentage of Urinary Recovery | 8.87 percentage | Geometric Coefficient of Variation 34.5 |
Primary
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
Population: SAS comprised of participants who had received at least 1 dose, even if incomplete, of study drug. Number analyzed is the number of participants with data available for analyses at the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Feces | Day 1- 0-24 hr | 0.06 mg | — |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Feces | Day 3- 24-48 hr | 0.54 mg | Geometric Coefficient of Variation 131.6 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Feces | Day 4- 48-72 hr | 63.35 mg | Geometric Coefficient of Variation 19.5 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Feces | Day 5- 72-96 hr | 12.92 mg | — |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Feces | Day 6- 96-120 hr | 4.82 mg | Geometric Coefficient of Variation 62.4 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Feces | Day 7- 120-144 hr | 0.32 mg | Geometric Coefficient of Variation 130 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Feces | Day 8- 144-168 hr | 0.26 mg | Geometric Coefficient of Variation 55.3 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Feces | Day 9- 168-192 hr | 0.47 mg | — |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Feces | Day 10- 192-216 hr | 0.16 mg | — |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Feces | Day 11- 216-240 hr | 0.15 mg | — |
Primary
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
Population: SAS comprised of participants who had received at least 1 dose, even if incomplete, of study drug. Number analyzed is the number of participants with data available for analyses at the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 6- 96-120 hr | 0.05 mg | Geometric Coefficient of Variation 50.4 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 1- 0-6 hr | 6.11 mg | Geometric Coefficient of Variation 41.4 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 1- 6-12 hr | 0.89 mg | Geometric Coefficient of Variation 36.9 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 2- 12-24 hr | 0.75 mg | Geometric Coefficient of Variation 31.8 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 3- 24-48 hr | 0.47 mg | Geometric Coefficient of Variation 82.6 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 4- 48-72 hr | 0.18 mg | Geometric Coefficient of Variation 74 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 5- 72-96 hr | 0.09 mg | Geometric Coefficient of Variation 52.4 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 7- 120-144 hr | 0.03 mg | Geometric Coefficient of Variation 48.5 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 8- 144-168 hr | 0.03 mg | Geometric Coefficient of Variation 42.1 |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 9- 168-192 hr | 0.02 mg | — |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 10- 192-216 hr | NA mg | — |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 11- 216-240 hr | NA mg | — |
| Part A: [14C] Subasumstat | Percentage Of Recovered Total Radioactivity (TRA) In Urine | Day 12- 240-264 hr | NA mg | — |
Secondary
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
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
Population: The PK analysis set was planned to include participants with sufficient dosing and PK data to reliably estimate at least one PK parameter. However, due to the low number of participants and missing plasma and whole blood samples for most of them, it would not have been possible to report the data generated from these samples without compromising participant privacy. Therefore, based on the Sponsor's decision, the collected samples were not analyzed and have been disposed of.
Secondary
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
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
Population: The PK analysis set was planned to include participants with sufficient dosing and PK data to reliably estimate at least one PK parameter. However, due to the low number of participants and missing plasma and whole blood samples for most of them, it would not have been possible to report the data generated from these samples without compromising participant privacy. Therefore, based on the Sponsor's decision, the collected samples were not analyzed and have been disposed of.
Secondary
Clearance (CL) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data
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
Population: The PK analysis set was planned to include participants with sufficient dosing and PK data to reliably estimate at least one PK parameter. However, due to the low number of participants and missing plasma and whole blood samples for most of them, it would not have been possible to report the data generated from these samples without compromising participant privacy. Therefore, based on the Sponsor's decision, the collected samples were not analyzed and have been disposed of.
Secondary
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
Population: The PK analysis set was planned to include participants with sufficient dosing and PK data to reliably estimate at least one PK parameter. However, due to the low number of participants and missing plasma and whole blood samples for most of them, it would not have been possible to report the data generated from these samples without compromising participant privacy. Therefore, based on the Sponsor's decision, the collected samples were not analyzed and have been disposed of.
Secondary
Cumulative Amount of Unchanged Subasumstat Excreted Into the Urine (Aeurine)
Cumulative amount of unchanged subasumstat was determined as percentage (%) of dose of subasumstat.
Time frame: Pre-dose and post-dose at 0-6 hours (hr) and 6-12 hr on Day 1, 12-24 hr on Day 2, 24-48 hr on Day 3, 48-72 hr on Day 4, 72-96 hr on Day 5 up to Day 14
Population: SAS comprised of participants who had received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: [14C] Subasumstat | Cumulative Amount of Unchanged Subasumstat Excreted Into the Urine (Aeurine) | 8.9 % of dose | Standard Deviation 2.8 |
Secondary
Number of Participants With Abnormal Electrocardiogram Findings
Abnormal laboratory values are those outside of normal range as assessed by the investigator.
Time frame: Up to approximately 8 months
Population: SAS comprised of participants who had received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: [14C] Subasumstat | Number of Participants With Abnormal Electrocardiogram Findings | 1 participants |
| Part B: Subasumstat | Number of Participants With Abnormal Electrocardiogram Findings | 2 participants |
Secondary
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.
Time frame: Up to approximately 8 months
Population: SAS comprised of participants who had received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: [14C] Subasumstat | Number of Participants With Abnormal Laboratory Values | Serum Chemistry | 3 participants |
| Part A: [14C] Subasumstat | Number of Participants With Abnormal Laboratory Values | Hematology | 3 participants |
| Part A: [14C] Subasumstat | Number of Participants With Abnormal Laboratory Values | Urinalysis | 0 participants |
| Part B: Subasumstat | Number of Participants With Abnormal Laboratory Values | Serum Chemistry | 2 participants |
| Part B: Subasumstat | Number of Participants With Abnormal Laboratory Values | Hematology | 2 participants |
| Part B: Subasumstat | Number of Participants With Abnormal Laboratory Values | Urinalysis | 1 participants |
Secondary
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. An 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.
Time frame: Up to approximately 8 months
Population: SAS comprised of participants who had received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: [14C] Subasumstat | Number of Participants With One or More Serious Adverse Events (SAEs) | 0 participants |
| Part B: Subasumstat | Number of Participants With One or More Serious Adverse Events (SAEs) | 1 participants |
Secondary
Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs)
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. A TEAE was defined as an AE that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug.
Time frame: Up to approximately 8 months
Population: SAS comprised of participants who had received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: [14C] Subasumstat | Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) | 3 participants |
| Part B: Subasumstat | Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) | 2 participants |
Secondary
Relative Percentage Excretory Metabolites in Urine
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 and Day 8: 168 hr
Population: SAS comprised of participants who had received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: [14C] Subasumstat | Relative Percentage Excretory Metabolites in Urine | 0.0 % of dose | Standard Deviation 0 |
Secondary
Relative Percentage of Circulatory Metabolites in Plasma
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 and Day 8: 168 hr
Population: The PK analysis set was planned to include participants with sufficient dosing and PK data to reliably estimate at least one PK parameter. However, due to the low number of participants and missing plasma and whole blood samples for most of them, it would not have been possible to report the data generated from these samples without compromising participant privacy. Therefore, based on the Sponsor's decision, the collected samples were not analyzed and have been disposed of.
Secondary
Relative Percentage of Excretory Metabolites in Feces
M1, M9 and M10 reported as categories were the names for the metabolites.
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 and Day 8: 168 hr
Population: SAS comprised of participants who had received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: [14C] Subasumstat | Relative Percentage of Excretory Metabolites in Feces | Metabolite: M1 | 6.9 % of dose | Standard Deviation 1.4 |
| Part A: [14C] Subasumstat | Relative Percentage of Excretory Metabolites in Feces | Metabolite: M9 | 2.5 % of dose | Standard Deviation 4.3 |
| Part A: [14C] Subasumstat | Relative Percentage of Excretory Metabolites in Feces | Metabolite: M10 | 12.3 % of dose | Standard Deviation 2.6 |
Secondary
Renal Clearance (CLR) for Subasumstat in Urine
Time frame: Pre-dose and post-dose at 0-6 hours (hr) and 6-12 hr on Day 1, 12-24 hr on Day 2, 24-48 hr on Day 3, 48-72 hr on Day 4, 72-96 hr on Day 5 up to Day 14
Population: Based on Primary Analysis results, lack of generalizability and accuracy of the urine analysis and missing data for relevant PK parameters, it would not have been possible to report the accurate data without compromising participant privacy. Therefore, based on the Sponsor's decision, the collected samples were not analyzed and have been disposed of.
Secondary
Terminal Disposition Phase Half-life (T1/2z) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data
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
Population: The PK analysis set was planned to include participants with sufficient dosing and PK data to reliably estimate at least one PK parameter. However, due to the low number of participants and missing plasma and whole blood samples for most of them, it would not have been possible to report the data generated from these samples without compromising participant privacy. Therefore, based on the Sponsor's decision, the collected samples were not analyzed and have been disposed of.
Secondary
Tmax: Time of First Occurrence of Cmax 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
Population: The PK analysis set was planned to include participants with sufficient dosing and PK data to reliably estimate at least one PK parameter. However, due to the low number of participants and missing plasma and whole blood samples for most of them, it would not have been possible to report the data generated from these samples without compromising participant privacy. Therefore, based on the Sponsor's decision, the collected samples were not analyzed and have been disposed of.
Secondary
Volume of Distribution at Steady-state (Vss) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data
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
Population: The PK analysis set was planned to include participants with sufficient dosing and PK data to reliably estimate at least one PK parameter. However, due to the low number of participants and missing plasma and whole blood samples for most of them, it would not have been possible to report the data generated from these samples without compromising participant privacy. Therefore, based on the Sponsor's decision, the collected samples were not analyzed and have been disposed of.