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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002832-42 | EudraCT Number |
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| Name | Class |
|---|---|
| Quotient Clinical | OTHER |
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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.
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:
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Regimen A | Experimental | Single-dose belumosudil 200 mg tablet in the fasted state |
|
| Regimen B | Experimental | Single-dose belumosudil 200 mg tablet in the fed state |
|
| Regimen C | Experimental | Single-dose belumosudil capsules (administered as two 100-mg capsules) in the fed state |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Belumosudil Tablet | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
To be eligible for study entry subjects has to satisfy all of the following 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:
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
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Quotient Clinical Limited | Ruddington Nottingham | NG116JS | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35238174 | Background | 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. |
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Enrollment: 23 subjects
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| FG001 | 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 |
| FG002 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| BG001 | Cohort BCA |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Not all subjects received each regimen. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose |
|
Approximately 1 month
Adverse events were classified into two categories: 1.Pre-dose AEs: AEs recorded at screening or with a start date and time prior to the first does of IMP and either do not continue after or do not worsen in intensity after the first dose of IMP; 2. Treatment-emergent adverse events (TEAEs): 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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Regimen A | Single-dose belumosudil 200 mg tablet in the fasted state | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cervical radiculopathy | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Olivier Schueller, Senior Vice President, CMC & Clinical Pharmacology | Kadmon Corporation, LLC | 833-900-5366 | olivier.schueller@kadmon.com |
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| ID | Term |
|---|---|
| C000718240 | belumosudil |
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| Belumosudil Capsule |
| Drug |
|
|
| 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 | 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 | 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 | 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 | 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 | 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. | 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. | Approximately 1 month |
| Illness of prohibited medication |
|
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 |
| BG002 | 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 |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Age, Continuous | Median | Full Range | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| BMI (body mass index) | Mean | Standard Deviation | kg/m^2 |
|
| BMI (body mass index) | Median | Full Range | kg/m^2 |
|
| Regimen B |
Single-dose belumosudil 200 mg tablet in the fed state Belumosudil Tablet |
|
|
| 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 | Not all subjects in either cohort had all AUC measurements | Posted | Geometric Mean | Geometric Coefficient of Variation | (ng*h)/mL | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose |
|
|
|
| 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 | Posted | Number | 90% Confidence Interval | Ratio of Adjusted Geometric Means | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose |
|
|
|
|
| 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 | Not all subjects were available for all bioavailability measurements. | Posted | Number | 90% Confidence Interval | Ratio of Adjusted Geometric Means | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose |
|
|
|
|
| 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 | Based on PK Population: Not all subjects received each regimen. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose |
|
|
|
| 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 | Not all subjects in either cohort had all AUC measurements | Posted | Geometric Mean | Geometric Coefficient of Variation | (ng*h)/mL | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose |
|
|
|
| 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 | Not all subjects had PK parameter lambda-z analyzed | Posted | Geometric Mean | Standard Deviation | 1/hour | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose |
|
|
|
| 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 | Not all subjects had all PK parameters analyzed | Posted | Geometric Mean | Standard Deviation | Hours | Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose |
|
|
|
| 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. | All subject who received at least one dose of belumosudil | Posted | Count of Participants | Participants | Approximately 1 month |
|
|
|
| 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. | Posted | Count of Participants | Participants | Approximately 1 month |
|
|
|
| 23 |
| 0 |
| 23 |
| 6 |
| 23 |
| EG001 | Regimen B | Single-dose belumosudil 200 mg tablet in the fed state Belumosudil Tablet | 0 | 20 | 0 | 20 | 3 | 20 |
| EG002 | Regimen C | Single-dose belumosudil 200 mg capsule (two 100-mg capsules) in the fed state | 0 | 22 | 0 | 22 | 5 | 22 |
| Headache | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (18.0) | Systematic Assessment |
|
| Influenza-like illness | General disorders | MedDRA (18.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (18.0) | Systematic Assessment |
|
| Blood creatinine phosphokinase increased | Investigations | MedDRA (18.0) | Systematic Assessment |
|
| Transaminase increased | Investigations | MedDRA (18.0) | Systematic Assessment |
|
| Atrioventricular block--2nd degree | Cardiac disorders | MedDRA (18.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
|
| Oropharyngeal | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
|
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.
| AUC(0-last): KD025m1 |
|
|
| AUC(0-last): KD025m2 |
|
|
| AUC(0-inf): KD025 |
|
|
| AUC(0-inf): KD025m1 |
|
|
| AUC(0-inf): KD025m2 |
|
|
| Cmax null hypothesis: Ratio of Adjusted Geometric Means = 100% | t-test, 2 sided | 0.23 | Ratio of Geometric Means (%) | 100 | 2-Sided | 90 | 80.00 | 125.00 | Equivalence | If the 90% confidence interval for the comparison of belumosudil tablet (test drug) vs. the belumosudil capsule (reference drug) is within the acceptance range 80.00% to 125.00%, then it is concluded that there is no effect on the use of belumosudi tablet compared to belumosudil capsule. | Intra-subject variability: 48.00% |
| AUC(0-last) |
|
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| AUC(0-inf) Null Hypothesis: Ratio of Adjusted Geometric Means = 100% | t-test, 2 sided | 0.16 | Ratio of Adjusted Geometric Means (%) | 100 | 2-Sided | 90 | 80.00 | 125.00 | Equivalence | If the 90% confidence interval for the comparison of belumosudil tablet (test drug) vs. the belumosudil capsule (reference drug) is within the acceptance range 80.00% to 125.00%, then it is concluded that there is no effect on the use of belumosudi tablet compared to belumosudil capsule. | Intra-subject variability; |
| AUC(0-last) Null Hypothesis: Ratio of Adjusted Geometric Means = 100% | t-test, 2 sided | < 0.001 | Ratio of Adjusted Geometric Means (%) | 100 | 2-Sided | 90 | 80.00 | 125.00 | Equivalence | If the 90% confidence interval for the comparison of fed vs. fasted is within the acceptance range 80.00% to 125.00%, then it is concluded that there is no effect of food on belumosudil tablets. | Intra-subject variability = 38.16% |
| AUC(0-last) Null Hypothesis: Ratio of Adjusted Geometric Means = 100% | t-test, 2 sided | 0.18 | Ratio of Adjusted Geometric Means (%) | 100 | 2-Sided | 90 | 80.00 | 125.00 | Intra-subject variability = 38.16% | Equivalence | If the 90% confidence interval for the comparison of belumosudil tablet (test drug) vs. the belumosudil capsule (reference drug) is within the acceptance range 80.00% to 125.00%, then it is concluded that there is no effect on the use of belumosudi tablet compared to belumosudil capsule. | Intra-subject variability = 38.16% |
| Cmax: KD025m1 |
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| Cmax: KD025m2 |
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| AUC(0-last): KD025m1 |
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| AUC(0-last): KD025m2 |
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| AUC(0-inf): KD025 |
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| AUC(0-inf): KD025m1 |
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| AUC(0-inf): KD025m2 |
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| KD025m1 |
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| KD025m2 |
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| KD025m1: t(1/2) |
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| KD025m2: t(1/2) |
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| KD025: MRT(0-last) |
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| KD025m1: MRT(0-last) |
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| KD025m2: MRT(0-last) |
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| KD025: MRT(0-inf) |
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| KD025m1: MRT(0-inf) |
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| KD025m2: MRT(0-inf) |
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| Reporting belumosudil-related TEAEs |
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| TEAEs Leading to Withdrawal |
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| Severe TEAEs |
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| Serious TEAEs |
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| TEAEs Leading to Death |
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| TEAEs Related to Belumosudil |
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| TEAEs Leading to Withdrawal |
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| Severe TEAEs |
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| Serious TEAEs (SAE) |
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| TEAEs Leading to Death |
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