Nuvisan GmbH
Neu-Ulm, 89231, Germany
NCT Number: NCT07214922
The main purpose of the study is to compare the Pharmacokinetics (PK), safety and tolerability of different manufacturing batches of M2951 tablet formulation relative to a reference batch under fasted conditions in healthy participants.
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Notify Me18 year–55 year
All sexes
Interventional
Phase 1
Neu-Ulm, 89231, Germany
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Participants will receive single dose of Treatment A in treatment period 1, 2, 3 or 4 under fasted conditions.
Other names: Evobrutinib
Participants will receive single dose of Treatment B in treatment period 1, 2, 3 or 4 under fasted conditions.
Other names: Evobrutinib
Participants will receive single dose of Treatment C in treatment period 1, 2, 3 or 4 under fasted conditions.
Other names: Evobrutinib
Participants will receive single dose of Treatment D in treatment period 1, 2, 3 or 4 under fasted conditions.
Other names: Evobrutinib
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7
Cmax was obtained directly from the concentration versus time curve.
Time frame: Up to 34 days
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE 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. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs.
Time frame: Up to 34 days
The Investigator assessed the severity of each AE and SAE reported during the study and assign it to one of the following categories: Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities; Severe: An event that prevents normal everyday activities. Do not confuse an AE that is assessed as severe with a SAE. Severe is a category used to rate the intensity of an event; both AEs and SAEs can be assessed as severe.
Time frame: Baseline (Pre-dose), 2 hours post-dose
Diastolic blood pressure and systolic blood pressure were measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.
Time frame: Baseline (Pre-dose), 2 hours post-dose
Temperature was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.
Time frame: Baseline (Pre-dose), 2 hours post-dose
Pulse rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.
Time frame: Baseline (Pre-dose), 2 hours post-dose
Respiratory rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.
Time frame: Baseline (Pre-dose), 2 hours post-dose
Heart rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions
Time frame: Baseline (Pre-dose), 2 hours post-dose
RR Duration, QT Duration, QTcF Duration, PR Duration, QRS Duration was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.
Time frame: Screening up to Day 8
Laboratory investigation included hematology, biochemistry and urinalysis. The number of participants with clinically significant changes from baseline in laboratory parameters were reported. Clinical significance was determined by the investigator.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7
The 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 (LLOQ). Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7
Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7
Terminal half-life was calculated as log2 divided by lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7
Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for Evobrutinib.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7
Vz/f is defined as the apparent volume of distribution during the terminal phase following extravascular administration for Evobrutinib.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7
Relative Bioavailability in percentage of each treatment (B, C, and D) in relation to the reference Treatment (A) was calculated as Frel = 100 multiplied by (AUC0-inf [treatment B, C, D]) multiplied by Dose [treatment A] divided by (AUC0-inf [treatment A]) multiplied by Dose [treatment B, C, D]. Treatment A to determine relative bioavailability.
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Industry
A Phase I, Open-Label Study of the Relative Bioavailability of Evobrutinib Tablet Manufacturing Batches in Healthy Participants
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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