Trial Outcomes & Findings for Human Absorption, Distribution and Metabolism Study (hAME) [14C]-KD025 (NCT NCT03907540)
NCT ID: NCT03907540
Last Updated: 2022-05-26
Results Overview
Apparent terminal elimination half-life (t\[1/2\] for Part 1: (Treatment A) KD025 200 mg tablet, fed (Day 1). then 1.75 hours later (Treatment B) \[14C\]-KD025 solution for infusion 20 microgm/mL (100 microgm in 5 mL) containing \<= 37 kilobecquerel as 15 min IV infusion 100 microgm, fed
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
5 participants
Primary outcome timeframe
Plasma samples belumosudil relative to oral dosing: 0,0.5,1,1.5,2,3,4,5,6,8,10,12,24,36, and 48 hours post-dosing. Plasma samples [14C]-KD025 relative to end infusion:-0.25,-0.16,-0.08,0,0.08,0.16,0.25,0.5,0.75,1,1.5,2,3,4,5,6,8,10,12,22,34, and 46 h
Results posted on
2022-05-26
Participant Flow
Participant milestones
| Measure |
All Subjects (Part 1 and Part 2)
Part 1: (Treatment A) KD025 200 mg tablet, fed (Day 1). then 1.75 hours later (Treatment B) \[14C\]-KD025 solution for infusion, 20 μg/mL (100 μg in 5 mL), containing not more than 37 kBq (1000 nCi) \[14C\], as a 15 min IV infusion, 100 μg, fed
Part 2: (Treatment C) Single \[14C\]-KD025 capsule 200 mg containing \<= 9.8 megabecquerel 14C, fed
|
|---|---|
|
Overall Study
STARTED
|
5
|
|
Overall Study
Completed Part 1
|
5
|
|
Overall Study
Completed Part 2
|
5
|
|
Overall Study
COMPLETED
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Human Absorption, Distribution and Metabolism Study (hAME) [14C]-KD025
Baseline characteristics by cohort
| Measure |
All Subjects
n=5 Participants
All subjects who received a single dose \[14C\]-KD025 and oral belumosudil tablet
|
|---|---|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=39 Participants
|
|
Body Mass Index (kg/m^2)
|
27.86 kg/m^2
STANDARD_DEVIATION 3.06 • n=39 Participants
|
|
Age, Continuous
|
53.0 Years
STANDARD_DEVIATION 8.7 • n=39 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=39 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=39 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: Plasma samples belumosudil relative to oral dosing: 0,0.5,1,1.5,2,3,4,5,6,8,10,12,24,36, and 48 hours post-dosing. Plasma samples [14C]-KD025 relative to end infusion:-0.25,-0.16,-0.08,0,0.08,0.16,0.25,0.5,0.75,1,1.5,2,3,4,5,6,8,10,12,22,34, and 46 hPopulation: All subjects
Apparent terminal elimination half-life (t\[1/2\] for Part 1: (Treatment A) KD025 200 mg tablet, fed (Day 1). then 1.75 hours later (Treatment B) \[14C\]-KD025 solution for infusion 20 microgm/mL (100 microgm in 5 mL) containing \<= 37 kilobecquerel as 15 min IV infusion 100 microgm, fed
Outcome measures
| Measure |
Part 1: Treatment A
n=5 Participants
Belumosudil 200 mg Tablet
|
Part 1: Treatment B
n=5 Participants
\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV (20 μg per mL)
|
Cumulative Total Ae (%)
Percentage of \[14C\]-KD025 200 mg oral capsule excreted overall
|
|---|---|---|---|
|
Part 1 Pharmacokinetics: t(1/2) for Belumosudil Tablet and [14C]-KD025 IV
|
5.298 Hours
Geometric Coefficient of Variation 66.7
|
5.857 Hours
Geometric Coefficient of Variation 35.8
|
—
|
SECONDARY outcome
Timeframe: Plasma samples belumosudil relative oral dosing: 0,0.5,1,1.5,2,3,4,5,6,7,8,10,12,24,36, and 48 hours post-dosing. Plasma samples [14C]-KD025 relative to end infusion:-0.25,-0.16,-0.08,0,0.08,0.16,0.25,0.5,0.75,1, 1.5,2,3,4,5,6,8,10,12,22,34,and 46 hPart 1: Time of maximum plasma concentration (Tmax) for belumosudil 200 mg oral tablet and \[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV
Outcome measures
| Measure |
Part 1: Treatment A
n=5 Participants
Belumosudil 200 mg Tablet
|
Part 1: Treatment B
n=5 Participants
\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV (20 μg per mL)
|
Cumulative Total Ae (%)
Percentage of \[14C\]-KD025 200 mg oral capsule excreted overall
|
|---|---|---|---|
|
Part 1 Pharmacokinetics: Tmax for Belumosudil Tablet and [14C]-KD025
|
2.000 Hours
Interval 1.0 to 4.0
|
0.248 Hours
Interval 0.24 to 0.25
|
—
|
SECONDARY outcome
Timeframe: Plasma samples belumosudil relative to oral dosing: 0,0.5,1,1.5,2,3,4,5,6,7,8,10,12,24,36, and 48 hours post-dosing.The maximum concentration (Cmax) of belumosudil 200 mg tablets
Outcome measures
| Measure |
Part 1: Treatment A
n=5 Participants
Belumosudil 200 mg Tablet
|
Part 1: Treatment B
\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV (20 μg per mL)
|
Cumulative Total Ae (%)
Percentage of \[14C\]-KD025 200 mg oral capsule excreted overall
|
|---|---|---|---|
|
Part 1 Pharmacokinetics: Cmax of Belumosudil Tablets
|
1870 ng/mL
Geometric Coefficient of Variation 36.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma samples for [14C]-KD025 relative to end of infusion:-0.25,-0.16,-0.08,0,0.08,0.16,0.25,0.5,0.75,1, 1.5,2,3,4,5,6,8,10,12,22,34,46 hours post-doseThe maximum concentration (Cmax) of belumosudil \[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV
Outcome measures
| Measure |
Part 1: Treatment A
n=5 Participants
Belumosudil 200 mg Tablet
|
Part 1: Treatment B
\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV (20 μg per mL)
|
Cumulative Total Ae (%)
Percentage of \[14C\]-KD025 200 mg oral capsule excreted overall
|
|---|---|---|---|
|
Part 1 Pharmacokinetics: Cmax of [14C]-KD025 IV
|
4480 (pg/mL)/(ng equiv/mL)
Geometric Coefficient of Variation 18.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma samples for belumosudil relative to oral dosing: 0,0.5,1,1.5,2,3,4,5,6,7,8,10,12,24,36, and 48 hours post-dosing.The area under the concentration-time curve from zero extrapolated to infinity (AUC\[0-inf\]) of belumosudil 200 mg tablets
Outcome measures
| Measure |
Part 1: Treatment A
n=5 Participants
Belumosudil 200 mg Tablet
|
Part 1: Treatment B
\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV (20 μg per mL)
|
Cumulative Total Ae (%)
Percentage of \[14C\]-KD025 200 mg oral capsule excreted overall
|
|---|---|---|---|
|
Part 1 Pharmacokinetics: AUC(0-inf) of Belumosudil Tablets
|
8300 (ng*h)/mL
Geometric Coefficient of Variation 40.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma samples for [14C]-KD025 relative to end of infusion:-0.25,-0.16,-0.08,0,0.08,0.16,0.25,0.5,0.75,1, 1.5,2,3,4,5,6,8,10,12,22,34,and 46 hours post-doseThe area under the concentration-time curve from zero extrapolated to infinity (AUC\[0-inf\]) of \[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV
Outcome measures
| Measure |
Part 1: Treatment A
n=5 Participants
Belumosudil 200 mg Tablet
|
Part 1: Treatment B
\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV (20 μg per mL)
|
Cumulative Total Ae (%)
Percentage of \[14C\]-KD025 200 mg oral capsule excreted overall
|
|---|---|---|---|
|
Part 1 Pharmacokinetics: AUC(0-inf) of [14C]-KD025 IV
|
6480 ((ng*h)/mL)/(ng equiv*h/mL)
Geometric Coefficient of Variation 29.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma samples for belumosudil relative to oral dosing: 0,0.5,1,1.5,2,3,4,5,6,7,8,10,12,24,36, and 48 hours post-dosing.The absolute bioavailability following oral administration of belumosudil 200 mg tablet, based on the area under the concentration-time curve from zero dosing extrapolated to infinity (AUC\[0-inf\])
Outcome measures
| Measure |
Part 1: Treatment A
n=5 Participants
Belumosudil 200 mg Tablet
|
Part 1: Treatment B
\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV (20 μg per mL)
|
Cumulative Total Ae (%)
Percentage of \[14C\]-KD025 200 mg oral capsule excreted overall
|
|---|---|---|---|
|
Part 1: Absolute Bioavailability of Belumosudil 200 mg Tablet
|
64 Percentage
|
—
|
—
|
SECONDARY outcome
Timeframe: Cumulative sample collection time frame 0-6 hours, 0-12 hours, 0-24 hours, 0-48 hours, 0-72 hours, 0-96 hours, 0-120 hours, 0-144 hours, 0-168 hours, 0-192 hours, 0-216 hours post-doseCumulative amount of total radioactivity excreted and recovered in urine, feces and total excreta (urine and feces combined) following dosing with \[14C\]-KD025 200 mg oral capsule.
Outcome measures
| Measure |
Part 1: Treatment A
n=5 Participants
Belumosudil 200 mg Tablet
|
Part 1: Treatment B
n=5 Participants
\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV (20 μg per mL)
|
Cumulative Total Ae (%)
n=5 Participants
Percentage of \[14C\]-KD025 200 mg oral capsule excreted overall
|
|---|---|---|---|
|
Part 2: Mass Balance Recovery Following 200 mg Oral Dose of [14C]-KD025 Capsule
0-24 (hours)
|
3.773 Percentage
|
27.431 Percentage
|
31.203 Percentage
|
|
Part 2: Mass Balance Recovery Following 200 mg Oral Dose of [14C]-KD025 Capsule
0-48 (hours)
|
3.933 Percentage
|
75.499 Percentage
|
79.432 Percentage
|
|
Part 2: Mass Balance Recovery Following 200 mg Oral Dose of [14C]-KD025 Capsule
0-72 (hours)
|
3.958 Percentage
|
81.597 Percentage
|
85.555 Percentage
|
|
Part 2: Mass Balance Recovery Following 200 mg Oral Dose of [14C]-KD025 Capsule
0-96 (hours)
|
3.966 Percentage
|
83.044 Percentage
|
87.010 Percentage
|
|
Part 2: Mass Balance Recovery Following 200 mg Oral Dose of [14C]-KD025 Capsule
0-216 (hours)
|
3.980 Percentage
|
84.553 Percentage
|
88.533 Percentage
|
|
Part 2: Mass Balance Recovery Following 200 mg Oral Dose of [14C]-KD025 Capsule
0-6 (hours)
|
2.194 Percentage
|
NA Percentage
Feces sample only collected once per day and reported in the 0-24 hour period.
|
NA Percentage
Feces sample only collected once per day and reported in the 0-24 hour period.
|
|
Part 2: Mass Balance Recovery Following 200 mg Oral Dose of [14C]-KD025 Capsule
0-12 (hours)
|
3.343 Percentage
|
NA Percentage
Feces sample only collected once per day and reported in the 0-24 hour period.
|
NA Percentage
Feces sample only collected once per day and reported in the 0-24 hour period.
|
|
Part 2: Mass Balance Recovery Following 200 mg Oral Dose of [14C]-KD025 Capsule
0-120 (hours)
|
3.972 Percentage
|
84.070 Percentage
|
88.042 Percentage
|
|
Part 2: Mass Balance Recovery Following 200 mg Oral Dose of [14C]-KD025 Capsule
0-144 (hours)
|
3.976 Percentage
|
84.340 Percentage
|
88.315 Percentage
|
|
Part 2: Mass Balance Recovery Following 200 mg Oral Dose of [14C]-KD025 Capsule
0-168 (hours)
|
3.977 Percentage
|
84.436 Percentage
|
88.413 Percentage
|
|
Part 2: Mass Balance Recovery Following 200 mg Oral Dose of [14C]-KD025 Capsule
0-192 (hours)
|
3.979 Percentage
|
84.493 Percentage
|
84.472 Percentage
|
SECONDARY outcome
Timeframe: Time Relative to Belumosudil Dosing: 0,0.5,1,1.5,2,3,4,5,6,8,10,12,24,36,48,72,96,120,144, and 168 hours post-doseTime of maximum concentration (Tmax) following a single oral dose of 200 mg \[14C\]-KD025 capsule
Outcome measures
| Measure |
Part 1: Treatment A
n=5 Participants
Belumosudil 200 mg Tablet
|
Part 1: Treatment B
\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV (20 μg per mL)
|
Cumulative Total Ae (%)
Percentage of \[14C\]-KD025 200 mg oral capsule excreted overall
|
|---|---|---|---|
|
Part 2 Pharmacokinetics: Tmax of 200 mg [14C]-KD025
|
2.000 Hours
Interval 1.5 to 2.05
|
—
|
—
|
SECONDARY outcome
Timeframe: Time Relative to Belumosudil Dosing: 0,0.5,1,1.5,2,3,4,5,6,8,10,12,24,36,48,72,96,120,144, and 168 hours post-doseApparent terminal elimination half-life (t\[1/2\]) following a single oral dose of 200 mg \[14C\]-KD025 capsule
Outcome measures
| Measure |
Part 1: Treatment A
n=5 Participants
Belumosudil 200 mg Tablet
|
Part 1: Treatment B
\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV (20 μg per mL)
|
Cumulative Total Ae (%)
Percentage of \[14C\]-KD025 200 mg oral capsule excreted overall
|
|---|---|---|---|
|
Part 2 Pharmacokinetics: t(1/2) of 200 mg [14C]-KD025
|
5.109 Hours
Geometric Coefficient of Variation 37.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Time Relative to Belumosudil Dosing: 0,0.5,1,1.5,2,3,4,5,6,8,10,12,24,36,48,72,96,120,144, and 168 hours post-doseMaximum concentration following a single oral dose of 200 mg \[14C\]-KD025 capsule
Outcome measures
| Measure |
Part 1: Treatment A
n=5 Participants
Belumosudil 200 mg Tablet
|
Part 1: Treatment B
\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV (20 μg per mL)
|
Cumulative Total Ae (%)
Percentage of \[14C\]-KD025 200 mg oral capsule excreted overall
|
|---|---|---|---|
|
Part 2 Pharmacokinetics: Cmax of 200 mg [14C]-KD025
|
1680 ng/mL
Geometric Coefficient of Variation 32.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Time Relative to Belumosudil Dosing: 0,0.5,1,1.5,2,3,4,5,6,8,10,12,24,36,48,72,96,120,144, and 168 hours post-doseArea under the concentration-time curve from zero dosing extrapolated to infinity following a single oral dose of 200 mg \[14C\]-KD025 capsule
Outcome measures
| Measure |
Part 1: Treatment A
n=5 Participants
Belumosudil 200 mg Tablet
|
Part 1: Treatment B
\[14C\]-KD025 at a dose of 100 μg in a 5 mL solution IV (20 μg per mL)
|
Cumulative Total Ae (%)
Percentage of \[14C\]-KD025 200 mg oral capsule excreted overall
|
|---|---|---|---|
|
Part 2 Pharmacokinetics: AUC(0-inf) of 200 mg [14C]-KD025
|
8100 (ng*h)/mL
Geometric Coefficient of Variation 37.0
|
—
|
—
|
Adverse Events
All Subjects
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
All Subjects
n=5 participants at risk
All subjects completing Part 1 and Part 2
|
|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
20.0%
1/5 • Number of events 1 • Up to 20 days
|
Additional Information
Olivier Schueller, Senior Vice President, CMC & Clinical Pharmacology
Kadmon Corporation
Phone: 724-778-6170
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding results. The sponsor cannot require changes to the study results in the communication except to remove sponsor's confidential information. Sponsor cannot unilaterally extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER