Clinical trial NCT03436394: Effect of Renal Impairment on Evobrutinib Pharmacokinetics (PK)
Official title: Phase I, Open-label, Single Dose Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics (PK) of Evobrutinib (M2951) Compared to Normal Renal Function in Male and Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: Renal Impairment
Evobrutinib
Pharmacokinetics
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2018-02-19
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The study will investigate the PK and safety of evobrutinib in subjects with different degree of renal impairment as compared to subjects with normal renal function.


Eligibility criteria: Inclusion Criteria:

* Male and Female subjects with total body weight between 50.0 and 100.0 kilograms(kg) (inclusive) and body mass index (BMI) between 19.0 and 36.0 kg per meter square (inclusive) at the time of the screening examination
* For subjects with impaired renal function: Subjects must have an eGFR according to the Modification of diet in renal disease (MDRD) equation of less than 90 mL per minute at screening and the possibility of stratification to one of the groups and a stable renal function as defined by either: if the time interval between screening and dosing is greater than 10 days, two eGFR with the second estimate within 20% of prior value or historical records of stable function over the past 3 months if within 20 percentage of screening value and within 10 days of dosing
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* History or presence of respiratory, gastrointestinal (including bariatric or other gastric surgeries, or other conditions that may affect drug absorption) hepatic (including hepatorenal syndrome), hematological, lymphatic, neurological (including seizures), cardiovascular (including ventricular dysfunction and congestive heart failure), psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders that may affect the safety of the subject.
* Clinical history of any autoimmune disorder
* Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to Screening, which might interfere with the objectives of the study or the study procedures
* History of any malignancy except superficial basal cell carcinoma treated for curative intent may be allowed
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Evobrutinib
timeFrame: Pre-dose up to 30 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Evobrutinib
timeFrame: Pre-dose up to 30 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) of Evobrutinib
timeFrame: Pre-dose up to 30 hours post-dose
Secondary outcomes:
measure: Occurrences of Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to Day 6
measure: Number of Subjects With TEAEs According to Severity
timeFrame: Day 1 up to Day 6
measure: Number of Subjects With Clinically Significant Abnormalities in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings
timeFrame: Day 1 up to Day 6
measure: Time to Reach the Maximum Plasma Concentration (tmax) of Evobrutinib
timeFrame: Pre-dose up to 30 hours post-dose
measure: Time Prior to the First Measurable (Non-Zero) Concentration (t lag) of Evobrutinib
timeFrame: Pre-dose up to 30 hours post-dose
measure: Terminal Rate Constant (λz) of Evobrutinib
timeFrame: Pre-dose up to 30 hours post-dose
measure: Terminal Half-Life (t1/2) of Evobrutinib
timeFrame: Pre-dose up to 30 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours After Dosing (AUC 0-24h) of Evobrutinib
timeFrame: Pre-dose up to 24 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours After Dosing (AUC 0-8h) of Evobrutinib
timeFrame: Pre-dose up to 8 hours post-dose
measure: Apparent Clearance (CL/f) of Evobrutinib
timeFrame: Pre-dose up to 30 hours post-dose
measure: Apparent Volume of Distribution During Terminal Phase (Vz/f) of Evobrutinib
timeFrame: Pre-dose up to 30 hours post-dose
measure: Amount of Unchanged Drug (Evobrutinib) Excreted in Urine During Collection Interval (0-8 hours) (Ae0-8h)
timeFrame: Pre-dose up to 8 hours post-dose
measure: Fraction of Administered Drug (Evobrutinib) Excreted in Urine (fe)
timeFrame: Pre-dose up to 30 hours post-dose
measure: Fraction of Unbound Drug (Evobrutinib) in the Plasma (fu)
timeFrame: Pre-dose up to 30 hours post-dose
measure: Renal Clearance of Evobrutinib (CLR)
timeFrame: Pre-dose up to 30 hours post-dose
measure: Non-Renal Clearance of Evobrutinib (CLNonR/f)
timeFrame: Pre-dose up to 30 hours post-dose
Other outcomes:
Locations:
city: Darmstadt
country: Germany
facility: Please Contact the Merck KGaA Communication Center
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: