Bioavailability
Conditions
Brief summary
Phase 1 bioavailability study to evaluate the pharmacokinetics (PK) and tolerability/safety of the belumosudil tablet formulation in the fasted and fed states and compared to the belumosudil capsule formulation in the fed state.
Detailed description
This is a Phase 1, 3-way, crossover, randomized, open-label study in healthy subjects designed to compare the bioavailability of belumosudil (previously known as KD025) tablet formulation administered in the fed and fasted states and to assess the relative bioavailability of belumosudil tablet and capsule formulations in the fed state. The primary objective of the study is to determine the PK parameters of belumosudil tablet formulation in the fed and fasted states. The secondary objectives of the study are: (1) to assess the relative bioavailability of a tablet (test) to capsule (reference formulation of belumosudil; (2) to assess and compare the variability in the maximum concentration (Cmax) and area under the concentration-time curve (AUC) for belumosudil treatments (belumosudil 200 mg tablet in the fasting state, belumosudil 200 mg tablet in the fed state, and belumosudil as two 100 mg capsules in the fed state); and (3) to provide additional safety and tolerability information for belumosudil. This is a single-center, open-label, randomized, single-dose, 3-period, 3-way, crossover study in healthy subjects. In each of 3 study periods, each subject receives 1 of the following single-dose treatments: * Regimen A: Belumosudil 200 mg tablet in the fasted state * Regimen B: Belumosudil 200 mg tablet in the fed state * Regimen C: Belumosudil 200 mg as two 100-mg capsules in the fed state Subjects are randomized to receive 1 dose of investigational product (IP; belumosudil tablet or capsule) in the morning of Day 1 in a randomized manner following an overnight fast or a high-fat breakfast. Administration is performed on Day 1 with an appropriate interval between subjects based on logistical requirements. Start time is determined based on logistics. Subjects undergo a screening visit in the 21 days preceding first dose. Subjects are admitted to the clinical unit on the evening prior to dosing (Day -1), remain on site until 24 hours post-dose, and return to the clinic at 36 and 48 hours post-dose for PK assessments. There is a minimum washout period of 6 days between each dose administration. All other meals are standardized for each of the in-clinic phases of the 3 treatment periods. Each period follows the same study design. The randomized cohorts for the 3-periods were as follows: * Cohort ABC: Regimen A (Period 1); Regimen B (Period 2); Regimen C (Period 3) * Cohort BCA: Regimen B (Period 1); Regimen C (Period 2); Regimen A (Period 3) * Cohort CAB: Regimen C (Period 1); Regimen A (Period 2); Regimen B (Period 3) A follow-up call is made 3 to 5 days after the final dose of IP. Planned enrollment is 24 subjects to insure there are 20 evaluable subjects. A subject is considered evaluable if (s)he completes treatment with fasted and fed tablet formulations (Regimens A and B) without major protocol deviations.
Interventions
DRUGBelumosudil Tablet
DRUGBelumosudil Capsule
Sponsors
Quotient Clinical
Kadmon Corporation, LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
To be eligible for study entry subjects has to satisfy all of the following criteria: 1. Healthy males 2. Aged 18 to 55 years of age 3. Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment (detailed medical history and a complete physical examination), ECG, and laboratory investigations (hematology, coagulation, clinical chemistry and urinalysis) 4. Body mass index 18.0-30.0 kg/m\^2, or if outside the range, considered not clinically significant by the Investigator 5. Willing and able to communicate and participate in the whole study 6. Provide written informed consent 7. Agree to use an adequate method of contraception for up to 90 days post discharge
Exclusion criteria
Subjects are excluded from the study if one of more of the following statements is applicable: 1. Participated in a clinical research study within the previous 3 months 2. Study site employees, or immediate family members of a study site or sponsor employee 3. Had been previously enrolled in this study 4. History of any drug or alcohol abuse in the past 2 years 5. Regular alcohol consumption \> 21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) 6. Current smokers and those who had smoked within the last 12 months. A breath carbon monoxide (CO) reading of greater than 10 ppm at screening 7. Did not have suitable veins for multiple venepunctures/cannulation as assessed by the Investigator at screening 8. Clinically significant abnormal biochemistry, hematology, coagulation, or urinalysis as judged by the Investigator 9. Positive drugs of abuse test result or alcohol breath test 10. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (Ab) or human immunodeficiency virus (HIV) results 11. History of any clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal (GI) disease that may have compromised the subject's safety or interfered with the objectives of the study as judged by the investigator 12. Subject had a history or presence of any of the following: * Active GI disease requiring therapy * Hepatic disease and/or alanine aminotransaminase (ALT) or aspartate aminotransaminase (AST) \> 1.5 × upper limit of normal (ULN) at screening * Renal disease and/or serum creatinine \> 1.5 × ULN at screening * Other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs 13. QT interval corrected using Fridericia's formula (QTcF) \> 450 msec at the screening or admission ECG 14. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients 15. Known sensitivity to ROCK2 inhibitor agents or to any of the constituents of the belumosudil formulation 16. Presence or history of clinically significant allergy requiring treatment, as judged by the Investigator. Hayfever is permitted unless it is active. 17. Donation or loss of \> 400 mL of blood within the previous 3 months 18. Taking or had taken any prescribed or over-the-counter drug (other than 4 g per day paracetamol) or herbal remedies in the 14 days before IP administration 19. Fails to satisfy the Investigator's discretion of fitness to participate or for any other reason Additional Restrictions 1. Abstain from alcohol during the 24 h prior to each admission until discharge from the clinic in each study period 2. Not to drink liquids or eat food containing grapefruit, cranberry, caffeine, or other xanthines from 24 hours prior to each admission until 48 hours post-dose 3. Refrain from eating food containing any seeds (e.g., poppy) for 48 hours before the screening visit and then from 48 h prior to each admission until discharge from the clinic for each study period 4. Not to take part in any unaccustomed strenuous exercise from 72 hours prior to the screening visit and then from 72 hours prior to admission until discharge from the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose | Maximum concentration (Cmax) of parent drug (KD025), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) when administering a single dose of belumosudil 200 mg tablet to subjects who are fasting (Regimen A) compared to administering a single dose of belumosudil 200 mg tablet to subjects who are fed (Regimen B) at 48 hours after dosing |
| Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose | Area under concentration-time curve from zero to last dose of belumosudil 200 mg tablets (AUC\[0-last\]) and from zero to infinity (AUC\[0-inf\]) for Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) when administering a single dose of belumosudil 200 mg tablet to subjects who are fasting (Regimen A) compared to administering a single dose of belumosudil 200 mg tablet to subjects who are fed (Regimen B) at 48 hours after dosing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Cmax for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose | Analysis of the maximum concentration (Cmax) of the relative bioavailability of Regimen B (belumosudil 200 mg tablet-fed) vs. Regimen A (belumosudil 200 mg tablet-fasting) and for Regimen B vs. Regimen C (belumosudil 200 mg capsule-fed) utilizing the Ratio of the Adjusted Geometric Means at 48 hours after dosing |
| Pharmacokinetics: AUCs for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose | Analysis of the area under concentration-time curve for zero to infinity (AUC\[0-inf\]), and zero to last dose (AUC\[0-last\]) of the relative bioavailability of Regimen B (belumosudil 200 mg tablet-fed) vs. Regimen A (belumosudil 200 mg tablet-fasting) and for Regimen B vs. Regimen C (belumosudil 200 mg capsule-fed) utilizing the Ratio of the Adjusted Geometric Means at 48 hours after dosing |
| Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose | Maximum concentration (Cmax) of parent drug (KD025), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) when administering a single dose of belumosudil 200 mg tablet to subjects who are fasting (Regimen A) compared to administering a single dose of belumosudil 200 mg tablet to subjects who are fed (Regimen B) compared to a single dose of belumosudil 200 mg capsule (two 100-mg capsules) to subjects who are fed (Regimen C) at 48 hours after dosing |
| Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose | Area under concentration curve from zero to last dose (AUC\[0-last\]) and from zero to infinity (AUC\[0-inf\]) for parent drug (KD025), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) when administering a single dose of belumosudil 200 mg tablet to subjects who are fasting (Regimen A) compared to administering a single dose of belumosudil 200 mg tablet to subjects who are fed (Regimen B) compared to administering a single dose of 200 mg capsule (two 100-mg capsules) to subjects who are fed at 48 hours after dosing |
| Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose | Slope of the regression line passing through the apparent elimination phase in a concentration-time plot (Lambda-z) for Regimen A, Regimen B, and Regimen C for for the parent drug (KD025), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) at 48 hours after dosing |
| Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose | Apparent elimination half-life (t\[1/2\]), mean residence time from zero to last dose (MRT\[0-last\]), and MRT for zero to infinity (MRT\[0-inf\]) for Regimen A, Regimen B, and Regimen C for for the parent drug (KD025), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) at 48 hours after dosing |
| Safety: Number of Subjects With TEAEs and SAEs | Approximately 1 month | Number of subjects with treatment-emergent adverse events (TEAEs), severity and relationship to belumosudil, serious adverse events (SAEs), TEAEs leading to withdrawal from study, and deaths. Treatment-emergent adverse events (TEAEs) are AEs that are not present before the first dose of IMP or that are present before the first dose of IMP but worsen in intensity during exposure to IMP. Severity: mild = 1; moderate = 2; severe = 3; life-threatening = 4; and death = 5. Related to belumosudil defined as possibly related, probably related, and related. |
| Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | Approximately 1 month | Total number of subjects who had treatment-emergent adverse events (TEAEs), TEAEs related to belumosudil, TEAEs leading to withdrawal of subject, severe TEAEs, serious TEAE (SAE), and TEAEs leading to death. Treatment-emergent adverse events (TEAEs) are AEs that are not present before the first dose of IMP or that are present before the first dose of IMP but worsen in intensity during exposure to IMP. Severity: mild = 1; moderate = 2; severe = 3; life-threatening = 4; and death = 5. Related to belumosudil defined as possibly related, probably related, and related. |
Countries
United Kingdom
Participant flow
Recruitment details
Enrollment: 23 subjects
Participants by arm
| Arm | Count |
|---|---|
| Cohort ABC Period 1: Single-dose Belumosudil 200 mg tablet fasted (Regimen A); Washout; Period 2: Single-dose Belumosudil 200 mg tablet fed (Regimen B); Washout; Period 3: Single-dose Belumosudil two 100-mg capsules, i.e., 200 mg (Regimen C) | 8 |
| Cohort BCA Period 1: Belumosudil 200 mg tablet fed; Washout; Period 2: Belumosudil 200 mg by capsule, i.e., two 100-mg capsules fed; Washout; Period 3: Belumosudil 200 mg tablet fasted | 8 |
| Cohort CAB Period 1: Single-dose Belumosudil 200 mg by capsule, i.e., two 100-mg capsules fed; Washout; Period 2: Single-dose Belumosudil 200 mg tablet fasted; Washout; Period 3: Single-dose Belumosudil 200 mg tablet fed | 7 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Illness of prohibited medication | 0 | 0 | 1 |
| Overall Study | Significant liver elevation | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort ABC | Cohort BCA | Cohort CAB | Total |
|---|---|---|---|---|
| Age, Continuous | 32.5 Years | 27.5 Years | 46.0 Years | 33.0 Years |
| BMI (body mass index) | 26.4 kg/m^2 | 26.0 kg/m^2 | 26.1 kg/m^2 | 26.15 kg/m^2 STANDARD_DEVIATION 2.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 7 Participants | 6 Participants | 20 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 7 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 20 | 0 / 22 |
| other Total, other adverse events | 6 / 23 | 3 / 20 | 5 / 22 |
| serious Total, serious adverse events | 0 / 23 | 0 / 20 | 0 / 22 |
Outcome results
Primary
Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose
Area under concentration-time curve from zero to last dose of belumosudil 200 mg tablets (AUC\[0-last\]) and from zero to infinity (AUC\[0-inf\]) for Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) when administering a single dose of belumosudil 200 mg tablet to subjects who are fasting (Regimen A) compared to administering a single dose of belumosudil 200 mg tablet to subjects who are fed (Regimen B) at 48 hours after dosing
Time frame: Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose
Population: Not all subjects in either cohort had all AUC measurements
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen A | Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | AUC(0-last): KD025 | 4520 (ng*h)/mL | Geometric Coefficient of Variation 121.3 |
| Regimen A | Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | AUC(0-last): KD025m1 | 19.8 (ng*h)/mL | Geometric Coefficient of Variation 150.6 |
| Regimen A | Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | AUC(0-last): KD025m2 | 550 (ng*h)/mL | Geometric Coefficient of Variation 133.3 |
| Regimen A | Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | AUC(0-inf): KD025 | 4910 (ng*h)/mL | Geometric Coefficient of Variation 146.9 |
| Regimen A | Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | AUC(0-inf): KD025m1 | 153 (ng*h)/mL | Geometric Coefficient of Variation 0 |
| Regimen A | Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | AUC(0-inf): KD025m2 | 691 (ng*h)/mL | Geometric Coefficient of Variation 76.7 |
| Regimen B | Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | AUC(0-inf): KD025m1 | 98.7 (ng*h)/mL | Geometric Coefficient of Variation 0 |
| Regimen B | Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | AUC(0-last): KD025 | 9750 (ng*h)/mL | Geometric Coefficient of Variation 49.3 |
| Regimen B | Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | AUC(0-inf): KD025 | 10100 (ng*h)/mL | Geometric Coefficient of Variation 52.9 |
| Regimen B | Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | AUC(0-last): KD025m1 | 45.2 (ng*h)/mL | Geometric Coefficient of Variation 95.3 |
| Regimen B | Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | AUC(0-inf): KD025m2 | 1370 (ng*h)/mL | Geometric Coefficient of Variation 62.6 |
| Regimen B | Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | AUC(0-last): KD025m2 | 1320 (ng*h)/mL | Geometric Coefficient of Variation 62.6 |
Primary
Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose
Maximum concentration (Cmax) of parent drug (KD025), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) when administering a single dose of belumosudil 200 mg tablet to subjects who are fasting (Regimen A) compared to administering a single dose of belumosudil 200 mg tablet to subjects who are fed (Regimen B) at 48 hours after dosing
Time frame: Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose
Population: Not all subjects received each regimen.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen A | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: KD025 | 821 ng/mL | Geometric Coefficient of Variation 129.5 |
| Regimen A | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: KD025m1 | 19.4 ng/mL | Geometric Coefficient of Variation 51.6 |
| Regimen A | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: KD025m2 | 173 ng/mL | Geometric Coefficient of Variation 122.6 |
| Regimen B | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: KD025 | 2100 ng/mL | Geometric Coefficient of Variation 49.8 |
| Regimen B | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: KD025m1 | 25.8 ng/mL | Geometric Coefficient of Variation 42 |
| Regimen B | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: KD025m2 | 412 ng/mL | Geometric Coefficient of Variation 63 |
Secondary
Pharmacokinetics: AUCs for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose
Analysis of the area under concentration-time curve for zero to infinity (AUC\[0-inf\]), and zero to last dose (AUC\[0-last\]) of the relative bioavailability of Regimen B (belumosudil 200 mg tablet-fed) vs. Regimen A (belumosudil 200 mg tablet-fasting) and for Regimen B vs. Regimen C (belumosudil 200 mg capsule-fed) utilizing the Ratio of the Adjusted Geometric Means at 48 hours after dosing
Time frame: Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose
Population: Not all subjects were available for all bioavailability measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Regimen A | Pharmacokinetics: AUCs for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose | AUC(0-inf) | 179.58 Ratio of Adjusted Geometric Means |
| Regimen A | Pharmacokinetics: AUCs for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose | AUC(0-last) | 187.92 Ratio of Adjusted Geometric Means |
| Regimen B | Pharmacokinetics: AUCs for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose | AUC(0-inf) | 118.43 Ratio of Adjusted Geometric Means |
| Regimen B | Pharmacokinetics: AUCs for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose | AUC(0-last) | 117.57 Ratio of Adjusted Geometric Means |
Comparison: AUC(0-inf) Null Hypothesis: Ratio of Adjusted Geometric Means = 100%p-value: <0.00190% CI: [80, 125]t-test, 2 sided
Comparison: AUC(0-inf) Null Hypothesis: Ratio of Adjusted Geometric Means = 100%p-value: 0.1690% CI: [80, 125]t-test, 2 sided
Comparison: AUC(0-last) Null Hypothesis: Ratio of Adjusted Geometric Means = 100%p-value: <0.00190% CI: [80, 125]t-test, 2 sided
Comparison: AUC(0-last) Null Hypothesis: Ratio of Adjusted Geometric Means = 100%p-value: 0.1890% CI: [80, 125]t-test, 2 sided
Secondary
Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose
Area under concentration curve from zero to last dose (AUC\[0-last\]) and from zero to infinity (AUC\[0-inf\]) for parent drug (KD025), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) when administering a single dose of belumosudil 200 mg tablet to subjects who are fasting (Regimen A) compared to administering a single dose of belumosudil 200 mg tablet to subjects who are fed (Regimen B) compared to administering a single dose of 200 mg capsule (two 100-mg capsules) to subjects who are fed at 48 hours after dosing
Time frame: Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose
Population: Not all subjects in either cohort had all AUC measurements
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen A | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-last): KD025m2 | 550 (ng*h)/mL | Geometric Coefficient of Variation 133.3 |
| Regimen A | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-inf): KD025m2 | 691 (ng*h)/mL | Geometric Coefficient of Variation 76.7 |
| Regimen A | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-inf): KD025 | 4910 (ng*h)/mL | Geometric Coefficient of Variation 146.9 |
| Regimen A | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-last): KD025m1 | 19.8 (ng*h)/mL | Geometric Coefficient of Variation 150.6 |
| Regimen A | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-last): KD025 | 4520 (ng*h)/mL | Geometric Coefficient of Variation 121.3 |
| Regimen A | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-inf): KD025m1 | 153 (ng*h)/mL | Geometric Coefficient of Variation 0 |
| Regimen B | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-last): KD025 | 9750 (ng*h)/mL | Geometric Coefficient of Variation 49.3 |
| Regimen B | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-last): KD025m1 | 45.2 (ng*h)/mL | Geometric Coefficient of Variation 95.3 |
| Regimen B | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-last): KD025m2 | 1320 (ng*h)/mL | Geometric Coefficient of Variation 62.6 |
| Regimen B | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-inf): KD025 | 10100 (ng*h)/mL | Geometric Coefficient of Variation 52.9 |
| Regimen B | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-inf): KD025m1 | 98.7 (ng*h)/mL | Geometric Coefficient of Variation 0 |
| Regimen B | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-inf): KD025m2 | 1370 (ng*h)/mL | Geometric Coefficient of Variation 62.6 |
| Regimen C | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-last): KD025m1 | 33.6 (ng*h)/mL | Geometric Coefficient of Variation 106.9 |
| Regimen C | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-inf): KD025m2 | 1420 (ng*h)/mL | Geometric Coefficient of Variation 47.7 |
| Regimen C | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-inf): KD025m1 | 213 (ng*h)/mL | Geometric Coefficient of Variation 0 |
| Regimen C | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-last): KD025m2 | 1000 (ng*h)/mL | Geometric Coefficient of Variation 95.5 |
| Regimen C | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-last): KD025 | 8650 (ng*h)/mL | Geometric Coefficient of Variation 42.7 |
| Regimen C | Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose | AUC(0-inf): KD025 | 8710 (ng*h)/mL | Geometric Coefficient of Variation 42.2 |
Secondary
Pharmacokinetics: Cmax for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose
Analysis of the maximum concentration (Cmax) of the relative bioavailability of Regimen B (belumosudil 200 mg tablet-fed) vs. Regimen A (belumosudil 200 mg tablet-fasting) and for Regimen B vs. Regimen C (belumosudil 200 mg capsule-fed) utilizing the Ratio of the Adjusted Geometric Means at 48 hours after dosing
Time frame: Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A | Pharmacokinetics: Cmax for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose | 225.02 Ratio of Adjusted Geometric Means |
| Regimen B | Pharmacokinetics: Cmax for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose | 119.38 Ratio of Adjusted Geometric Means |
Comparison: Cmax null hypothesis: Ratio of Adjusted Geometric Means = 100%p-value: <0.00190% CI: [80, 125]t-test, 2 sided
Comparison: Cmax null hypothesis: Ratio of Adjusted Geometric Means = 100%p-value: 0.2390% CI: [80, 125]t-test, 2 sided
Secondary
Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose
Maximum concentration (Cmax) of parent drug (KD025), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) when administering a single dose of belumosudil 200 mg tablet to subjects who are fasting (Regimen A) compared to administering a single dose of belumosudil 200 mg tablet to subjects who are fed (Regimen B) compared to a single dose of belumosudil 200 mg capsule (two 100-mg capsules) to subjects who are fed (Regimen C) at 48 hours after dosing
Time frame: Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose
Population: Based on PK Population: Not all subjects received each regimen.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen A | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: KD025m1 | 19.4 ng/mL | Geometric Coefficient of Variation 51.6 |
| Regimen A | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: Parent Drug KD025 | 821 ng/mL | Geometric Coefficient of Variation 129.5 |
| Regimen A | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: KD025m2 | 173 ng/mL | Geometric Coefficient of Variation 122.6 |
| Regimen B | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: KD025m1 | 25.8 ng/mL | Geometric Coefficient of Variation 42 |
| Regimen B | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: Parent Drug KD025 | 2100 ng/mL | Geometric Coefficient of Variation 49.8 |
| Regimen B | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: KD025m2 | 412 ng/mL | Geometric Coefficient of Variation 63 |
| Regimen C | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: Parent Drug KD025 | 1750 ng/mL | Geometric Coefficient of Variation 38.2 |
| Regimen C | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: KD025m2 | 289 ng/mL | Geometric Coefficient of Variation 76.5 |
| Regimen C | Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | Cmax: KD025m1 | 20.6 ng/mL | Geometric Coefficient of Variation 38.2 |
Secondary
Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose
Slope of the regression line passing through the apparent elimination phase in a concentration-time plot (Lambda-z) for Regimen A, Regimen B, and Regimen C for for the parent drug (KD025), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) at 48 hours after dosing
Time frame: Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose
Population: Not all subjects had PK parameter lambda-z analyzed
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen A | Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m1 | 0.3618 1/hour | Standard Deviation 0 |
| Regimen A | Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025 | 0.0622 1/hour | Standard Deviation 1.5848 |
| Regimen A | Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m2 | 0.4159 1/hour | Standard Deviation 1.5248 |
| Regimen B | Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m1 | 0.3608 1/hour | Standard Deviation 0 |
| Regimen B | Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025 | 0.0993 1/hour | Standard Deviation 1.5293 |
| Regimen B | Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m2 | 0.3291 1/hour | Standard Deviation 1.7326 |
| Regimen C | Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025 | 0.0967 1/hour | Standard Deviation 1.4594 |
| Regimen C | Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m2 | 0.2523 1/hour | Standard Deviation 1.7385 |
| Regimen C | Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m1 | 0.1275 1/hour | Standard Deviation 0 |
Secondary
Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose
Apparent elimination half-life (t\[1/2\]), mean residence time from zero to last dose (MRT\[0-last\]), and MRT for zero to infinity (MRT\[0-inf\]) for Regimen A, Regimen B, and Regimen C for for the parent drug (KD025), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) at 48 hours after dosing
Time frame: Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose
Population: Not all subjects had all PK parameters analyzed
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen A | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025: MRT(0-last) | 7.25 Hours | Standard Deviation 1.39 |
| Regimen A | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m1: t(1/2) | 1.92 Hours | Standard Deviation 0 |
| Regimen A | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m2: MRT(0-last) | 3.03 Hours | Standard Deviation 1.32 |
| Regimen A | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m1: MRT(0-last) | 1.70 Hours | Standard Deviation 1.61 |
| Regimen A | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m2: MRT(0-inf) | 3.46 Hours | Standard Deviation 1.3 |
| Regimen A | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m1: MRT(0-inf) | 3.38 Hours | Standard Deviation 0 |
| Regimen A | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m2: t(1/2) | 1.67 Hours | Standard Deviation 1.52 |
| Regimen A | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025: t(1/2) | 11.16 Hours | Standard Deviation 1.58 |
| Regimen A | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025: MRT(0-inf) | 9.35 Hours | Standard Deviation 1.33 |
| Regimen B | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025: t(1/2) | 6.98 Hours | Standard Deviation 1.53 |
| Regimen B | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m1: t(1/2) | 1.92 Hours | Standard Deviation 0 |
| Regimen B | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m2: t(1/2) | 2.11 Hours | Standard Deviation 1.73 |
| Regimen B | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025: MRT(0-last) | 5.70 Hours | Standard Deviation 1.27 |
| Regimen B | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m1: MRT(0-last) | 2.45 Hours | Standard Deviation 1.61 |
| Regimen B | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m2: MRT(0-last) | 3.99 Hours | Standard Deviation 1.45 |
| Regimen B | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025: MRT(0-inf) | 6.40 Hours | Standard Deviation 1.27 |
| Regimen B | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m1: MRT(0-inf) | 4.39 Hours | Standard Deviation 0 |
| Regimen B | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m2: MRT(0-inf) | 4.35 Hours | Standard Deviation 1.46 |
| Regimen C | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m2: t(1/2) | 2.75 Hours | Standard Deviation 1.74 |
| Regimen C | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025: t(1/2) | 7.16 Hours | Standard Deviation 1.46 |
| Regimen C | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025: MRT(0-inf) | 7.18 Hours | Standard Deviation 1.24 |
| Regimen C | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m1: t(1/2) | 5.44 Hours | Standard Deviation 0 |
| Regimen C | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m2: MRT(0-inf) | 4.86 Hours | Standard Deviation 1.4 |
| Regimen C | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m1: MRT(0-last) | 2.79 Hours | Standard Deviation 1.57 |
| Regimen C | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025: MRT(0-last) | 6.21 Hours | Standard Deviation 1.22 |
| Regimen C | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m1: MRT(0-inf) | 8.26 Hours | Standard Deviation 0 |
| Regimen C | Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose | KD025m2: MRT(0-last) | 4.44 Hours | Standard Deviation 1.34 |
Secondary
Safety: Number of Subjects With TEAEs and SAEs
Number of subjects with treatment-emergent adverse events (TEAEs), severity and relationship to belumosudil, serious adverse events (SAEs), TEAEs leading to withdrawal from study, and deaths. Treatment-emergent adverse events (TEAEs) are AEs that are not present before the first dose of IMP or that are present before the first dose of IMP but worsen in intensity during exposure to IMP. Severity: mild = 1; moderate = 2; severe = 3; life-threatening = 4; and death = 5. Related to belumosudil defined as possibly related, probably related, and related.
Time frame: Approximately 1 month
Population: All subject who received at least one dose of belumosudil
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Regimen A | Safety: Number of Subjects With TEAEs and SAEs | Serious TEAEs | 0 Participants |
| Regimen A | Safety: Number of Subjects With TEAEs and SAEs | Reporting belumosudil-related TEAEs | 1 Participants |
| Regimen A | Safety: Number of Subjects With TEAEs and SAEs | TEAEs Leading to Death | 0 Participants |
| Regimen A | Safety: Number of Subjects With TEAEs and SAEs | TEAEs Leading to Withdrawal | 3 Participants |
| Regimen A | Safety: Number of Subjects With TEAEs and SAEs | Severe TEAEs | 1 Participants |
| Regimen A | Safety: Number of Subjects With TEAEs and SAEs | At least 1 TEAE | 6 Participants |
| Regimen B | Safety: Number of Subjects With TEAEs and SAEs | TEAEs Leading to Withdrawal | 0 Participants |
| Regimen B | Safety: Number of Subjects With TEAEs and SAEs | Reporting belumosudil-related TEAEs | 0 Participants |
| Regimen B | Safety: Number of Subjects With TEAEs and SAEs | Serious TEAEs | 0 Participants |
| Regimen B | Safety: Number of Subjects With TEAEs and SAEs | Severe TEAEs | 0 Participants |
| Regimen B | Safety: Number of Subjects With TEAEs and SAEs | TEAEs Leading to Death | 0 Participants |
| Regimen B | Safety: Number of Subjects With TEAEs and SAEs | At least 1 TEAE | 3 Participants |
| Regimen C | Safety: Number of Subjects With TEAEs and SAEs | TEAEs Leading to Death | 0 Participants |
| Regimen C | Safety: Number of Subjects With TEAEs and SAEs | Reporting belumosudil-related TEAEs | 0 Participants |
| Regimen C | Safety: Number of Subjects With TEAEs and SAEs | Severe TEAEs | 0 Participants |
| Regimen C | Safety: Number of Subjects With TEAEs and SAEs | TEAEs Leading to Withdrawal | 0 Participants |
| Regimen C | Safety: Number of Subjects With TEAEs and SAEs | At least 1 TEAE | 5 Participants |
| Regimen C | Safety: Number of Subjects With TEAEs and SAEs | Serious TEAEs | 0 Participants |
| Overall | Safety: Number of Subjects With TEAEs and SAEs | TEAEs Leading to Withdrawal | 3 Participants |
| Overall | Safety: Number of Subjects With TEAEs and SAEs | At least 1 TEAE | 9 Participants |
| Overall | Safety: Number of Subjects With TEAEs and SAEs | Reporting belumosudil-related TEAEs | 1 Participants |
| Overall | Safety: Number of Subjects With TEAEs and SAEs | TEAEs Leading to Death | 0 Participants |
| Overall | Safety: Number of Subjects With TEAEs and SAEs | Severe TEAEs | 1 Participants |
| Overall | Safety: Number of Subjects With TEAEs and SAEs | Serious TEAEs | 0 Participants |
Secondary
Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death
Total number of subjects who had treatment-emergent adverse events (TEAEs), TEAEs related to belumosudil, TEAEs leading to withdrawal of subject, severe TEAEs, serious TEAE (SAE), and TEAEs leading to death. Treatment-emergent adverse events (TEAEs) are AEs that are not present before the first dose of IMP or that are present before the first dose of IMP but worsen in intensity during exposure to IMP. Severity: mild = 1; moderate = 2; severe = 3; life-threatening = 4; and death = 5. Related to belumosudil defined as possibly related, probably related, and related.
Time frame: Approximately 1 month
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Regimen A | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | All TEAEs | 7 Participants |
| Regimen A | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | TEAEs Leading to Withdrawal | 3 Participants |
| Regimen A | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | TEAEs Related to Belumosudil | 1 Participants |
| Regimen A | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | Severe TEAEs | 1 Participants |
| Regimen A | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | Serious TEAEs (SAE) | 0 Participants |
| Regimen A | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | TEAEs Leading to Death | 0 Participants |
| Regimen B | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | Serious TEAEs (SAE) | 0 Participants |
| Regimen B | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | TEAEs Related to Belumosudil | 0 Participants |
| Regimen B | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | TEAEs Leading to Withdrawal | 0 Participants |
| Regimen B | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | All TEAEs | 3 Participants |
| Regimen B | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | TEAEs Leading to Death | 0 Participants |
| Regimen B | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | Severe TEAEs | 0 Participants |
| Regimen C | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | TEAEs Leading to Death | 0 Participants |
| Regimen C | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | Serious TEAEs (SAE) | 0 Participants |
| Regimen C | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | Severe TEAEs | 0 Participants |
| Regimen C | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | TEAEs Related to Belumosudil | 0 Participants |
| Regimen C | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | All TEAEs | 6 Participants |
| Regimen C | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | TEAEs Leading to Withdrawal | 0 Participants |
| Overall | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | All TEAEs | 16 Participants |
| Overall | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | TEAEs Related to Belumosudil | 1 Participants |
| Overall | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | Severe TEAEs | 1 Participants |
| Overall | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | Serious TEAEs (SAE) | 0 Participants |
| Overall | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | TEAEs Leading to Withdrawal | 3 Participants |
| Overall | Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death | TEAEs Leading to Death | 0 Participants |