Trial Outcomes & Findings for PK Study of Xevinapant (Debio 1143) in Healthy East Asian Participants (NCT NCT05519540)
NCT ID: NCT05519540
Last Updated: 2025-08-20
Results Overview
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).
COMPLETED
PHASE1
24 participants
Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose
2025-08-20
Participant Flow
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.
Participant milestones
| Measure |
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
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
12
|
|
Overall Study
COMPLETED
|
12
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
PK Study of Xevinapant (Debio 1143) in Healthy East Asian Participants
Baseline characteristics by cohort
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
31 Years
STANDARD_DEVIATION 7.1 • n=5 Participants
|
29 Years
STANDARD_DEVIATION 6.6 • n=7 Participants
|
30 Years
STANDARD_DEVIATION 6.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: 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.
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).
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sample Time (AUC0-tlast) of Xevinapant (Debio 1143)
|
9780 hours*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 34.6
|
10200 hours*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 21.4
|
PRIMARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Xevinapant (Debio 1143)
|
9860 h*ng/mL
Geometric Coefficient of Variation 34.4
|
10200 h*ng/mL
Geometric Coefficient of Variation 21.3
|
PRIMARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
Cmax was obtained directly from concentration versus time curve.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Xevinapant (Debio 1143)
|
2070 ng/mL
Geometric Coefficient of Variation 35.6
|
2160 ng/mL
Geometric Coefficient of Variation 32.9
|
SECONDARY outcome
Timeframe: Up to Day 8Population: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Related TEAE's
TEAEs
|
3 Participants
|
5 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Related TEAE's
Serious TEAE
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Related TEAE's
Related TEAE's
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1) up to Day 8Population: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity
Moderate TEAE
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity
Mild TEAEs
|
3 Participants
|
4 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity
Severe TEAE's
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1) up to Day 8Population: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values
Hematology
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values
Biochemistry
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values
Urinalysis
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1) up to Day 8Population: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1) up to Day 8Population: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of Xevinapant (Debio 1143)
|
9160 h*ng/mL
Geometric Coefficient of Variation 34.3
|
9460 h*ng/mL
Geometric Coefficient of Variation 20.6
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
Tmax was obtained directly from the plasma concentration versus time curve.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Xevinapant (Debio 1143)
|
0.750 hours
Interval 0.5 to 2.5
|
1.00 hours
Interval 0.5 to 1.5
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Apparent Terminal Half-Life (t1/2) of Xevinapant (Debio 1143)
|
9.38 hours
Geometric Coefficient of Variation 21.2
|
10.5 hours
Geometric Coefficient of Variation 28.7
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Apparent Clearance (CL/f) of Xevinapant (Debio 1143)
|
20.3 liter per hour
Geometric Coefficient of Variation 34.4
|
19.6 liter per hour
Geometric Coefficient of Variation 21.3
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Xevinapant (Debio 1143)
|
274 liter
Geometric Coefficient of Variation 36.1
|
296 liter
Geometric Coefficient of Variation 27.6
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
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).
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t Last) of Metabolite D-1143-MET1
|
13800 hours*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 28.3
|
14400 hours*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 34.1
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
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).
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of Metabolite D-1143-MET1
|
13000 h*ng/mL
Geometric Coefficient of Variation 27.4
|
13400 h*ng/mL
Geometric Coefficient of Variation 31.7
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metabolite D-1143-MET1
|
13800 h*ng/mL
Geometric Coefficient of Variation 28.2
|
14500 h*ng/mL
Geometric Coefficient of Variation 34.1
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
Cmax was obtained directly from concentration versus time curve.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Metabolite D-1143-MET1
|
1240 ng/mL
Geometric Coefficient of Variation 22.2
|
1240 ng/mL
Geometric Coefficient of Variation 21.5
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
Tmax was obtained directly from the plasma concentration versus time curve.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite D-1143-MET1
|
3.00 hours
Interval 2.0 to 4.0
|
3.00 hours
Interval 2.5 to 4.0
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Apparent Terminal Half-Life (t1/2) of Metabolite D-1143-MET1
|
5.23 hours
Geometric Coefficient of Variation 17.3
|
7.30 hours
Geometric Coefficient of Variation 54.4
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Metabolite-to-parent Molar Ratio for AUC0-t (MR_AUC0-t) of Xevinapant and D-1143-MET1
|
1.66 ratio
Geometric Coefficient of Variation 40.9
|
1.68 ratio
Geometric Coefficient of Variation 31.7
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
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.
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Metabolite-to-parent Molar Ratio for AUC0-inf (MR_AUC0-inf) of Xevinapant and D-1143-MET1
|
1.65 ratio
Geometric Coefficient of Variation 40.5
|
1.67 ratio
Geometric Coefficient of Variation 31.6
|
SECONDARY outcome
Timeframe: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdosePopulation: The PK Analysis Set included all participants who received at least one dose of study intervention and provided at least one measurable postdose concentration.
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
Outcome measures
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 Participants
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)
n=12 Participants
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Metabolite-to-parent Molar Ratio for Cmax (MR_Cmax) of Xevinapant and D-1143-MET1
|
0.704 ratio
Geometric Coefficient of Variation 42.7
|
0.679 ratio
Geometric Coefficient of Variation 31.7
|
Adverse Events
Group 1: Japanese Participants: Xevinapant (Debio 1143)
Group 2: Non-Japanese East Asian Participants: Xevinapant (Debio 1143)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group 1: Japanese Participants: Xevinapant (Debio 1143)
n=12 participants at risk
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)
n=12 participants at risk
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
|
|---|---|---|
|
Gastrointestinal disorders
Retching
|
0.00%
0/12 • Up to Day 8
|
8.3%
1/12 • Number of events 1 • Up to Day 8
|
|
General disorders
Catheter site bruise
|
0.00%
0/12 • Up to Day 8
|
8.3%
1/12 • Number of events 1 • Up to Day 8
|
|
Infections and infestations
Infection
|
0.00%
0/12 • Up to Day 8
|
8.3%
1/12 • Number of events 1 • Up to Day 8
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.3%
1/12 • Number of events 1 • Up to Day 8
|
0.00%
0/12 • Up to Day 8
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • Number of events 2 • Up to Day 8
|
0.00%
0/12 • Up to Day 8
|
|
Nervous system disorders
Somnolence
|
0.00%
0/12 • Up to Day 8
|
8.3%
1/12 • Number of events 1 • Up to Day 8
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/12 • Up to Day 8
|
8.3%
1/12 • Number of events 1 • Up to Day 8
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/12 • Up to Day 8
|
8.3%
1/12 • Number of events 1 • Up to Day 8
|
|
Skin and subcutaneous tissue disorders
Palmar erythema
|
8.3%
1/12 • Number of events 1 • Up to Day 8
|
0.00%
0/12 • Up to Day 8
|
Additional Information
Communication Center
Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place