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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-002182-15 | EudraCT Number |
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| Name | Class |
|---|---|
| Merck KGaA, Darmstadt, Germany | INDUSTRY |
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The purpose of this study was to evaluate the pharmacokinetics (PK) of Xevinapant (Debio 1143) and its metabolite D-1143-MET1 as well as safety and tolerability of Xevinapant (Debio 1143) in healthy East Asian participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: Japanese Participants: Xevinapant (Debio 1143) | Experimental | Xevinapant (Debio 1143) was administered in Healthy Japnaese participants at a dose of 200 milligrams (mg), orally under fasted conditions. |
|
| Group 2: Non-Japanese East Asian Participants: Xevinapant (Debio 1143) | Experimental | Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Xevinapant (Debio 1143) | Drug | All participants (Japanese and non-Japanese) received a single oral dose of 200mg xevinapant (Debio 1143) on Day 1 under fasted condition. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sample Time (AUC0-tlast) of Xevinapant (Debio 1143) | The area under the concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down). | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Xevinapant (Debio 1143) | The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at t last , as estimated using the linear regression from Terminal first order (elimination) rate constant (Lambda z) determination. AUC0-inf = AUC0-t plus Clast pred/lambda z. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Maximum Observed Plasma Concentration (Cmax) of Xevinapant (Debio 1143) | Cmax was obtained directly from concentration versus time curve. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Related TEAE's | An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both serious TEAEs and non-serious TEAEs. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Labcorp Clinical Research Unit Limited | Leeds | United Kingdom |
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| Label | URL |
|---|---|
| Trial Awareness and Transparency website | View source |
| Medical Information Location Map - Med Info Contacts | View source |
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We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
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A total of 47 participants were screened, of which 24 participants (12 Japanese participants and 12 non-Japanese East Asian participants) were enrolled in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1: Japanese Participants: Xevinapant (Debio 1143) | Xevinapant (Debio 1143) was administered in Healthy Japnaese participants at a dose of 200 milligrams (mg), orally under fasted conditions |
| FG001 | Group 2: Non-Japanese East Asian Participants: Xevinapant (Debio 1143) | Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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The safety analysis set included all participants who were administered any dose of any study intervention.
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1: Japanese Participants: Xevinapant (Debio 1143) | Xevinapant (Debio 1143) was administered in Healthy Japnaese participants at a dose of 200 milligrams (mg), orally under fasted conditions |
| BG001 | Group 2: Non-Japanese East Asian Participants: Xevinapant (Debio 1143) |
| Units | Counts |
|---|---|
| Participants |
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| 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 | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sample Time (AUC0-tlast) of Xevinapant (Debio 1143) | The area under the concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down). | The Pharmacokinetics (PK) Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*nanogram per milliliter (h*ng/mL) | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
|
Up to Day 8
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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 | Group 1: Japanese Participants: Xevinapant (Debio 1143) | Xevinapant (Debio 1143) was administered in Healthy Japnaese participants at a dose of 200 milligrams (mg), orally under fasted conditions |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Retching | Gastrointestinal disorders | MedDRA 25.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Communication Center | Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@emdgroup.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 10, 2022 | Jul 31, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 6, 2022 | Jul 31, 2025 | SAP_001.pdf |
| ID | Term |
|---|---|
| C559144 | N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamide |
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| Up to Day 8 |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity | Severity of TEAEs were graded using Qualitative Toxicity Scale, as follows: Mild: Participant is aware of the event or symptom, but the event or symptom is easily tolerated; Moderate: Participant experiences sufficient discomfort to interfere with or reduce his or her usual level of activity; Severe: Significant impairment of functioning: the participant is unable to carry out his or her usual activities. Number of participants with TEAEs by severity were reported. | Baseline (Day 1) up to Day 8 |
| Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values | The laboratory measurements included hematology, blood chemistry and urinalysis. Number of participants with clinically significant changes from baseline in laboratory values were reported. Clinically Significance was decided by investigator. | Baseline (Day 1) up to Day 8 |
| Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | The 12-lead ECG recordings were obtained after 5 minutes of rest in a semi-supine position. ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, QT and QTc intervals. Number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported. Clinically significance was decided by investigator. | Baseline (Day 1) up to Day 8 |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Vital sign assessment included blood pressure, pulse rate, body temperature and respiration rate. Number of participants with clinically significant changes from baseline in vital signs were reported. Clinically significance was decided by investigator. | Baseline (Day 1) up to Day 8 |
| Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of Xevinapant (Debio 1143) | AUC0-24 is defined as the area under the concentration-time curve (AUC) from time zero (= dosing time) to 24 hours. AUC0-24 was calculated using the mixed log-linear trapezoidal rule. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Xevinapant (Debio 1143) | Tmax was obtained directly from the plasma concentration versus time curve. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Apparent Terminal Half-Life (t1/2) of Xevinapant (Debio 1143) | t1/2 was the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. Terminal first order (elimination) rate constant was determined from the terminal slope of the log-transformed concentration curve using linear regression on terminal data points of the curve. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Apparent Clearance (CL/f) of Xevinapant (Debio 1143) | The apparent total body clearance of study intervention following extravascular administration, taking into account the fraction of dose absorbed. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Apparent Volume of Distribution During Terminal Phase (Vz/f) of Xevinapant (Debio 1143) | The apparent volume of distribution during the terminal phase following extravascular administration, based on the fraction of dose absorbed. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t Last) of Metabolite D-1143-MET1 | The area under the concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down). | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of Metabolite D-1143-MET1 | The area under the concentration-time curve (AUC) from time zero (= dosing time) to 24 hours. Calculated using the mixed log-linear trapezoidal rule (linear up, log down). | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metabolite D-1143-MET1 | The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at t last , as estimated using the linear regression from Terminal first order (elimination) rate constant (Lambda z) determination. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Maximum Observed Plasma Concentration (Cmax) of Metabolite D-1143-MET1 | Cmax was obtained directly from concentration versus time curve. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite D-1143-MET1 | Tmax was obtained directly from the plasma concentration versus time curve. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Apparent Terminal Half-Life (t1/2) of Metabolite D-1143-MET1 | t1/2 was the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. Terminal first order (elimination) rate constant was determined from the terminal slope of the log-transformed concentration curve using linear regression on terminal data points of the curve. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Metabolite-to-parent Molar Ratio for AUC0-t (MR_AUC0-t) of Xevinapant and D-1143-MET1 | AUC0-tlast Molar Ratio is the ratio of AUC0-t molar values of the metabolite compared to the parent calculated by dividing AUC0-t molar values of metabolite D-1143-MET1 with those of xevinapant. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Metabolite-to-parent Molar Ratio for AUC0-inf (MR_AUC0-inf) of Xevinapant and D-1143-MET1 | AUC0-inf last Molar Ratio is the ratio of AUC0-inf molar values of the metabolite compared to the parent calculated by dividing AUC0-inf molar values of metabolite D-1143-MET1 with those of xevinapant. | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
| Metabolite-to-parent Molar Ratio for Cmax (MR_Cmax) of Xevinapant and D-1143-MET1 | Cmax Molar Ratio is the ratio of cmax molar values of the metabolite compared to the parent calculated by dividing Cmax molar values of metabolite D-1143-MET1 with those of xevinapant | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Group 2: Non-Japanese East Asian Participants: Xevinapant (Debio 1143) | Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions. |
|
|
| Primary | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Xevinapant (Debio 1143) | The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at t last , as estimated using the linear regression from Terminal first order (elimination) rate constant (Lambda z) determination. AUC0-inf = AUC0-t plus Clast pred/lambda z. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Xevinapant (Debio 1143) | Cmax was obtained directly from concentration versus time curve. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
|
|
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Related TEAE's | An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both serious TEAEs and non-serious TEAEs. | The safety analysis set included all participants who were administered any dose of any study intervention. | Posted | Count of Participants | Participants | Up to Day 8 |
|
|
|
| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity | Severity of TEAEs were graded using Qualitative Toxicity Scale, as follows: Mild: Participant is aware of the event or symptom, but the event or symptom is easily tolerated; Moderate: Participant experiences sufficient discomfort to interfere with or reduce his or her usual level of activity; Severe: Significant impairment of functioning: the participant is unable to carry out his or her usual activities. Number of participants with TEAEs by severity were reported. | The safety analysis set included all participants who were administered any dose of any study intervention. | Posted | Count of Participants | Participants | Baseline (Day 1) up to Day 8 |
|
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| Secondary | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values | The laboratory measurements included hematology, blood chemistry and urinalysis. Number of participants with clinically significant changes from baseline in laboratory values were reported. Clinically Significance was decided by investigator. | The safety analysis set included all participants who were administered any dose of any study intervention. | Posted | Count of Participants | Participants | Baseline (Day 1) up to Day 8 |
|
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| Secondary | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | The 12-lead ECG recordings were obtained after 5 minutes of rest in a semi-supine position. ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, QT and QTc intervals. Number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported. Clinically significance was decided by investigator. | The safety analysis set included all participants who were administered any dose of any study intervention. | Posted | Count of Participants | Participants | Baseline (Day 1) up to Day 8 |
|
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| Secondary | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Vital sign assessment included blood pressure, pulse rate, body temperature and respiration rate. Number of participants with clinically significant changes from baseline in vital signs were reported. Clinically significance was decided by investigator. | The safety analysis set included all participants who were administered any dose of any study intervention. | Posted | Count of Participants | Participants | Baseline (Day 1) up to Day 8 |
|
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| Secondary | Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of Xevinapant (Debio 1143) | AUC0-24 is defined as the area under the concentration-time curve (AUC) from time zero (= dosing time) to 24 hours. AUC0-24 was calculated using the mixed log-linear trapezoidal rule. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
|
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| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Xevinapant (Debio 1143) | Tmax was obtained directly from the plasma concentration versus time curve. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Median | Full Range | hours | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
|
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| Secondary | Apparent Terminal Half-Life (t1/2) of Xevinapant (Debio 1143) | t1/2 was the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. Terminal first order (elimination) rate constant was determined from the terminal slope of the log-transformed concentration curve using linear regression on terminal data points of the curve. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
|
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| Secondary | Apparent Clearance (CL/f) of Xevinapant (Debio 1143) | The apparent total body clearance of study intervention following extravascular administration, taking into account the fraction of dose absorbed. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
|
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| Secondary | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Xevinapant (Debio 1143) | The apparent volume of distribution during the terminal phase following extravascular administration, based on the fraction of dose absorbed. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
|
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| Secondary | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t Last) of Metabolite D-1143-MET1 | The area under the concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down). | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*nanogram per milliliter (h*ng/mL) | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
|
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| Secondary | Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of Metabolite D-1143-MET1 | The area under the concentration-time curve (AUC) from time zero (= dosing time) to 24 hours. Calculated using the mixed log-linear trapezoidal rule (linear up, log down). | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose |
|
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| Secondary | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metabolite D-1143-MET1 | The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at t last , as estimated using the linear regression from Terminal first order (elimination) rate constant (Lambda z) determination. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
|
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of Metabolite D-1143-MET1 | Cmax was obtained directly from concentration versus time curve. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
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| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite D-1143-MET1 | Tmax was obtained directly from the plasma concentration versus time curve. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Median | Full Range | hours | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
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| Secondary | Apparent Terminal Half-Life (t1/2) of Metabolite D-1143-MET1 | t1/2 was the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. Terminal first order (elimination) rate constant was determined from the terminal slope of the log-transformed concentration curve using linear regression on terminal data points of the curve. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
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| Secondary | Metabolite-to-parent Molar Ratio for AUC0-t (MR_AUC0-t) of Xevinapant and D-1143-MET1 | AUC0-tlast Molar Ratio is the ratio of AUC0-t molar values of the metabolite compared to the parent calculated by dividing AUC0-t molar values of metabolite D-1143-MET1 with those of xevinapant. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
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| Secondary | Metabolite-to-parent Molar Ratio for AUC0-inf (MR_AUC0-inf) of Xevinapant and D-1143-MET1 | AUC0-inf last Molar Ratio is the ratio of AUC0-inf molar values of the metabolite compared to the parent calculated by dividing AUC0-inf molar values of metabolite D-1143-MET1 with those of xevinapant. | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
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| Secondary | Metabolite-to-parent Molar Ratio for Cmax (MR_Cmax) of Xevinapant and D-1143-MET1 | Cmax Molar Ratio is the ratio of cmax molar values of the metabolite compared to the parent calculated by dividing Cmax molar values of metabolite D-1143-MET1 with those of xevinapant | The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose |
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| 0 |
| 12 |
| 0 |
| 12 |
| 3 |
| 12 |
| EG001 | Group 2: Non-Japanese East Asian Participants: Xevinapant (Debio 1143) | Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions. | 0 | 12 | 0 | 12 | 5 | 12 |
| Catheter site bruise | General disorders | MedDRA 25.1 | Non-systematic Assessment |
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| Infection | Infections and infestations | MedDRA 25.1 | Non-systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 25.1 | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 25.1 | Non-systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Non-systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Non-systematic Assessment |
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| Palmar erythema | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Non-systematic Assessment |
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Not provided
Not provided
| Related TEAE's |
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| Severe TEAE's |
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| Urinalysis |
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