Effect of Renal Impairment on Evobrutinib Pharmacokinetics (PK)

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: Evobrutinib

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Darmstadt, Germany, 64293
    • Please contact the Merck KGaA Communication Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Evobrutinib: Normal Renal Function; Subjects with estimated glomerular filtration rate (eGFR) greater than or equal to (>=) 90 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) will receive a single oral dose of evobrutinib under fasting conditions.	Drug: Evobrutinib; Subjects will be administered a single oral dose of evobrutinib under fasting conditions.; Other Names: M2951; MSC2364447C
EXPERIMENTAL: Evobrutinib: Severe Renal Impairment; Subjects with eGFR less than (<) 30 mL/min/1.73 m^2 will receive a single oral dose of evobrutinib under fasting conditions.	Drug: Evobrutinib; Subjects will be administered a single oral dose of evobrutinib under fasting conditions.; Other Names: M2951; MSC2364447C
EXPERIMENTAL: Evobrutinib: Moderate Renal Impairment; Subjects with eGFR >= to 30 mL/min/1.73 m^2 and < 60 mL/min/1.73 m^2 will receive a single oral dose of evobrutinib under fasting conditions.	Drug: Evobrutinib; Subjects will be administered a single oral dose of evobrutinib under fasting conditions.; Other Names: M2951; MSC2364447C
EXPERIMENTAL: Evobrutinib: Mild Renal Impairment; Subjects with eGFR >= to 60 mL/min/1.73 m^2 and < 90 mL/min/1.73 m^2 will receive a single oral dose of evobrutinib under fasting conditions.	Drug: Evobrutinib; Subjects will be administered a single oral dose of evobrutinib under fasting conditions.; Other Names: M2951; MSC2364447C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Evobrutinib	Pre-dose up to 30 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Evobrutinib	Pre-dose up to 30 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib	Pre-dose up to 30 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrences of Treatment-emergent Adverse Events (TEAEs)		Day 1 up to Day 6
Number of Subjects With TEAEs According to Severity		Day 1 up to Day 6
Number of Subjects With Clinically Significant Abnormalities in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings	Number of subjects with clinically significant abnormalities will be reported.	Day 1 up to Day 6
Time to Reach the Maximum Plasma Concentration (tmax) of Evobrutinib		Pre-dose up to 30 hours post-dose
Time Prior to the First Measurable (Non-Zero) Concentration (t lag) of Evobrutinib		Pre-dose up to 30 hours post-dose
Terminal Rate Constant (λz) of Evobrutinib		Pre-dose up to 30 hours post-dose
Terminal Half-Life (t1/2) of Evobrutinib		Pre-dose up to 30 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours After Dosing (AUC 0-24h) of Evobrutinib		Pre-dose up to 24 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours After Dosing (AUC 0-8h) of Evobrutinib		Pre-dose up to 8 hours post-dose
Apparent Clearance (CL/f) of Evobrutinib		Pre-dose up to 30 hours post-dose
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Evobrutinib		Pre-dose up to 30 hours post-dose
Amount of Unchanged Drug (Evobrutinib) Excreted in Urine During Collection Interval (0-8 hours) (Ae0-8h)		Pre-dose up to 8 hours post-dose
Fraction of Administered Drug (Evobrutinib) Excreted in Urine (fe)		Pre-dose up to 30 hours post-dose
Fraction of Unbound Drug (Evobrutinib) in the Plasma (fu)		Pre-dose up to 30 hours post-dose
Renal Clearance of Evobrutinib (CLR)		Pre-dose up to 30 hours post-dose
Non-Renal Clearance of Evobrutinib (CLNonR/f)		Pre-dose up to 30 hours post-dose

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 21, 2018
• Primary Completion (ACTUAL): February 22, 2019
• Study Completion (ACTUAL): February 22, 2019

Study Registration Dates

• First Submitted: February 6, 2018
• First Submitted That Met QC Criteria: February 15, 2018
• First Posted (ACTUAL): February 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 16, 2019
• Last Update Submitted That Met QC Criteria: May 15, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Evobrutinib; Pharmacokinetics; Renal Impairment
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: MS200527_0026; 2017-004102-18 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No