CompletedNCT02557139Updated May 25, 2022Results posted

Bioavailability of Belumosudil (KD025) in Healthy Male Subjects

A Phase 1 interventional study of Belumosudil Tablet and Belumosudil Capsule in Bioavailability, sponsored by Kadmon Corporation, LLC. Completed at 1 site in United Kingdom. Open to male participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-05-25.

Sponsored by Kadmon Corporation, LLC · Phase 1, Interventional, and Other

Phase: Phase 1
Study type: Interventional
Enrollment: 23
Allocation: Randomized
Ages: 18 Years to 55 Years
Sex: Male

Study 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.

Read the 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.

Conditions studied

Bioavailability

In context

Lead sponsor

Kadmon Corporation, LLC is the lead sponsor of 20 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: Male
Accepts healthy volunteers: Yes

Inclusion criteria

To be eligible for study entry subjects has to satisfy all of the following criteria:

Healthy males
Aged 18 to 55 years of age
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)
Body mass index 18.0-30.0 kg/m\^2, or if outside the range, considered not clinically significant by the Investigator
Willing and able to communicate and participate in the whole study
Provide written informed consent
Agree to use an adequate method of contraception for up to 90 days post discharge

Exclusion criteria

Exclusion Criteria

Subjects are excluded from the study if one of more of the following statements is applicable:

Participated in a clinical research study within the previous 3 months
Study site employees, or immediate family members of a study site or sponsor employee
Had been previously enrolled in this study
History of any drug or alcohol abuse in the past 2 years
Regular alcohol consumption > 21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
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
Did not have suitable veins for multiple venepunctures/cannulation as assessed by the Investigator at screening
Clinically significant abnormal biochemistry, hematology, coagulation, or urinalysis as judged by the Investigator
Positive drugs of abuse test result or alcohol breath test
Positive hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (Ab) or human immunodeficiency virus (HIV) results
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
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
QT interval corrected using Fridericia's formula (QTcF) > 450 msec at the screening or admission ECG
Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
Known sensitivity to ROCK2 inhibitor agents or to any of the constituents of the belumosudil formulation
Presence or history of clinically significant allergy requiring treatment, as judged by the Investigator. Hayfever is permitted unless it is active.
Donation or loss of > 400 mL of blood within the previous 3 months
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
Fails to satisfy the Investigator's discretion of fitness to participate or for any other reason

Additional Restrictions

Abstain from alcohol during the 24 h prior to each admission until discharge from the clinic in each study period
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
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
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

Study design

Phase: Phase 1
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 23 participants (actual)

Study arms

Experimental
Regimen A
Single-dose belumosudil 200 mg tablet in the fasted state
Drug: Belumosudil Tablet
Experimental
Regimen B
Single-dose belumosudil 200 mg tablet in the fed state
Drug: Belumosudil Tablet
Experimental
Regimen C
Single-dose belumosudil capsules (administered as two 100-mg capsules) in the fed state
Drug: Belumosudil Capsule

Interventions

DrugBelumosudil Tablet
Also known as: Rezurock (brand), SLx-2119
DrugBelumosudil Capsule
Also known as: Rezurock (brand), SLx-2119

What researchers measure

Primary outcomes

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
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

Secondary outcomes

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
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
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
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
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
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
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
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

Results

Posted Oct 20, 2021

Participant flow

Enrollment: 23 subjects

Participant flow — Overall Study
Milestone	Cohort ABC	Cohort BCA	Cohort CAB
Started	8	8	7
Completed	6	8	5
Not completed	2	0	2
Withdrew: Significant liver elevation	1	0	1
Withdrew: Withdrawal by subject	1	0	0
Withdrew: Illness of prohibited medication	0	0	1

Outcome measures

PrimaryPharmacokinetics: 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
Reported as:: Geometric mean · ng/mL

Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose
ng/mL	Regimen A	Regimen B
Cmax: KD025	821 ± 129.5	2100 ± 49.8
Cmax: KD025m1	19.4 ± 51.6	25.8 ± 42.0
Cmax: KD025m2	173 ± 122.6	412 ± 63.0

PrimaryPharmacokinetics: 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
Reported as:: Geometric mean · (ng*h)/mL

Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose
(ng*h)/mL	Regimen A	Regimen B
AUC(0-last): KD025	4520 ± 121.3	9750 ± 49.3
AUC(0-last): KD025m1	19.8 ± 150.6	45.2 ± 95.3
AUC(0-last): KD025m2	550 ± 133.3	1320 ± 62.6
AUC(0-inf): KD025	4910 ± 146.9	10100 ± 52.9
AUC(0-inf): KD025m1	153 ± 0	98.7 ± 0
AUC(0-inf): KD025m2	691 ± 76.7	1370 ± 62.6

SecondaryPharmacokinetics: 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
Reported as:: Number · Ratio of Adjusted Geometric Means

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
Ratio of Adjusted Geometric Means	Regimen B/Regimen A	Regimen B/Regimen C
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 (176.08 to 287.57)	119.38 (93.41 to 152.56)

Statistical analysis

Regimen B/Regimen A · t-test, 2 sided · p = < 0.001 · Ratio of adjusted geometric means (%): 100 · 90% CI 80.00 to 125.00
Regimen B/Regimen C · t-test, 2 sided · p = 0.23 · Ratio of geometric means (%): 100 · 90% CI 80.00 to 125.00

SecondaryPharmacokinetics: 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
Reported as:: Number · Ratio of Adjusted Geometric Means

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
Ratio of Adjusted Geometric Means	Regimen B/Regimen A	Regimen B/Regimen C
AUC(0-inf)	179.58 (143.16 to 225.26)	118.43 (97.16 to 144.36)
AUC(0-last)	187.92 (154.07 to 229.21)	117.57 (96.40 to 143.40)

Statistical analysis

Regimen B/Regimen A · t-test, 2 sided · p = <0.001 · Ratio of adjusted geometric means (%): 100 · 90% CI 80.00 to 125.00
Regimen B/Regimen C · t-test, 2 sided · p = 0.16 · Ratio of adjusted geometric means (%): 100 · 90% CI 80.00 to 125.00
Regimen B/Regimen A · t-test, 2 sided · p = < 0.001 · Ratio of adjusted geometric means (%): 100 · 90% CI 80.00 to 125.00
Regimen B/Regimen C · t-test, 2 sided · p = 0.18 · Ratio of adjusted geometric means (%): 100 · 90% CI 80.00 to 125.00Intra-subject variability = 38.16%

SecondaryPharmacokinetics: 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

Time frame:: Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose
Reported as:: Geometric mean · ng/mL

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
ng/mL	Regimen A	Regimen B	Regimen C
Cmax: Parent Drug KD025	821 ± 129.5	2100 ± 49.8	1750 ± 38.2
Cmax: KD025m1	19.4 ± 51.6	25.8 ± 42.0	20.6 ± 38.2
Cmax: KD025m2	173 ± 122.6	412 ± 63.0	289 ± 76.5

SecondaryPharmacokinetics: 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
Reported as:: Geometric mean · (ng*h)/mL

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
(ng*h)/mL	Regimen A	Regimen B	Regimen C
AUC(0-last): KD025	4520 ± 121.3	9750 ± 49.3	8650 ± 42.7
AUC(0-last): KD025m1	19.8 ± 150.6	45.2 ± 95.3	33.6 ± 106.9
AUC(0-last): KD025m2	550 ± 133.3	1320 ± 62.6	1000 ± 95.5
AUC(0-inf): KD025	4910 ± 146.9	10100 ± 52.9	8710 ± 42.2
AUC(0-inf): KD025m1	153 ± 0	98.7 ± 0	213 ± 0
AUC(0-inf): KD025m2	691 ± 76.7	1370 ± 62.6	1420 ± 47.7

SecondaryPharmacokinetics: 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
Reported as:: Geometric mean · 1/hour

Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose
1/hour	Regimen A	Regimen B	Regimen C
KD025	0.0622 ± 1.5848	0.0993 ± 1.5293	0.0967 ± 1.4594
KD025m1	0.3618 ± 0	0.3608 ± 0	0.1275 ± 0
KD025m2	0.4159 ± 1.5248	0.3291 ± 1.7326	0.2523 ± 1.7385

SecondaryPharmacokinetics: 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
Reported as:: Geometric mean · Hours

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
Hours	Regimen A	Regimen B	Regimen C
KD025: t(1/2)	11.16 ± 1.58	6.98 ± 1.53	7.16 ± 1.46
KD025m1: t(1/2)	1.92 ± 0	1.92 ± 0	5.44 ± 0
KD025m2: t(1/2)	1.67 ± 1.52	2.11 ± 1.73	2.75 ± 1.74
KD025: MRT(0-last)	7.25 ± 1.39	5.70 ± 1.27	6.21 ± 1.22
KD025m1: MRT(0-last)	1.70 ± 1.61	2.45 ± 1.61	2.79 ± 1.57
KD025m2: MRT(0-last)	3.03 ± 1.32	3.99 ± 1.45	4.44 ± 1.34
KD025: MRT(0-inf)	9.35 ± 1.33	6.40 ± 1.27	7.18 ± 1.24
KD025m1: MRT(0-inf)	3.38 ± 0	4.39 ± 0	8.26 ± 0
KD025m2: MRT(0-inf)	3.46 ± 1.30	4.35 ± 1.46	4.86 ± 1.40

SecondarySafety: 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
Reported as:: Count of participants · Participants

Safety: Number of Subjects With TEAEs and SAEs
Participants	Regimen A	Regimen B	Regimen C	Overall
At least 1 TEAE	6	3	5	9
Reporting belumosudil-related TEAEs	1	0	0	1
TEAEs Leading to Withdrawal	3	0	0	3
Severe TEAEs	1	0	0	1
Serious TEAEs	0	0	0	0
TEAEs Leading to Death	0	0	0	0

SecondarySafety: 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
Reported as:: Count of participants · Participants

Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death
Participants	Regimen A	Regimen B	Regimen C	Overall
All TEAEs	7	3	6	16
TEAEs Related to Belumosudil	1	0	0	1
TEAEs Leading to Withdrawal	3	0	0	3
Severe TEAEs	1	0	0	1
Serious TEAEs (SAE)	0	0	0	0
TEAEs Leading to Death	0	0	0	0

Adverse events

Collected over Approximately 1 month. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Regimen A	0/23 (0%)	0/23 (0%)	6/23 (26.1%)
Regimen B	0/20 (0%)	0/20 (0%)	3/20 (15%)
Regimen C	0/22 (0%)	0/22 (0%)	5/22 (22.7%)

Most frequent other events

Showing 10 of 15

Most frequent other events
Event	Regimen A	Regimen B	Regimen C
HeadacheNervous system disorders	0/23	1/20	1/22
NasopharyngitisInfections and infestations	0/23	1/20	0/22
OropharyngealRespiratory, thoracic and mediastinal disorders	0/23	1/20	0/22
ParesthesiaNervous system disorders	0/23	0/20	1/22
SomnolenceNervous system disorders	0/23	0/20	1/22
FatigueGeneral disorders	0/23	0/20	1/22
Musculoskeletal painMusculoskeletal and connective tissue disorders	0/23	0/20	1/22
Rash macularSkin and subcutaneous tissue disorders	0/23	0/20	1/22
Cervical radiculopathyNervous system disorders	1/23	0/20	0/22
Influenza-like illnessGeneral disorders	1/23	0/20	0/22

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	Cohort ABC	Cohort BCA	Cohort CAB	Total
Mean	34.1 ± 11.0	32.3 ± 12.4	43.0 ± 9.0	36.2 ± 11.5

Age, Continuous
Age, Continuous(Years)	Cohort ABC	Cohort BCA	Cohort CAB	Total
Median	32.5 (20 to 53)	27.5 (21 to 50)	46.0 (30 to 54)	33.0 (20 to 54)

Sex: Female, Male
Sex: Female, Male(Participants)	Cohort ABC	Cohort BCA	Cohort CAB	Total
Female	0	0	0	0
Male	8	8	7	23

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Cohort ABC	Cohort BCA	Cohort CAB	Total
American Indian or Alaska Native	0	0	0	0
Asian	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	1	1	1	3
White	7	7	6	20
More than one race	0	0	0	0
Unknown or Not Reported	0	0	0	0

BMI (body mass index)
BMI (body mass index)(kg/m^2)	Cohort ABC	Cohort BCA	Cohort CAB	Total
Mean	26.19 ± 2.67	25.79 ± 2.43	26.53 ± 3.35	26.15 ± 2.70

BMI (body mass index)
BMI (body mass index)(kg/m^2)	Cohort ABC	Cohort BCA	Cohort CAB	Total
Median	26.4 (22.4 to 29.3)	26.0 (22.6 to 28.7)	26.1 (22.1 to 30.0)	26.10 (22.1 to 30.0)

Study locations

1 site

Quotient Clinical Limited
Ruddington Nottingham, NG116JS, United Kingdom

References and documents

Publications

Schueller O, McDermott J, Evans P, Lohmer L, Alabanza A, Patel J. Phase 1 Studies to Evaluate the Food Effect and Relative Bioavailability of Tablet and Capsule Formulations of Belumosudil in Healthy Adult Subjects. Clin Pharmacol Drug Dev. 2022 Jul;11(7):807-814. doi: 10.1002/cpdd.1083. Epub 2022 Mar 2. PubMed 35238174 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 25, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02557139
Lead sponsor: Kadmon Corporation, LLC
Collaborators: Quotient Clinical
Responsible party: Sponsor
First posted: Sep 23, 2015
Start date: Sep 2015
Primary completion: Oct 12, 2015
Completion: Oct 12, 2015
Results posted: Oct 20, 2021
Last update: May 25, 2022

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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