Effect of Renal Impairment on Evobrutinib Pharmacokinetics (PK)

Renal Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03436394
• Other study ID #: MS200527_0026
• Secondary ID: 2017-004102-18
• Status: Completed
• Phase: Phase 1
• Start date: March 21, 2018
• Est. completion date: February 22, 2019

Study information

• Verified date: May 2019
• Source: Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: February 22, 2019
• Est. primary completion date: February 22, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• Evobrutinib
Subjects will be administered a single oral dose of evobrutinib under fasting conditions.

Locations

Country	Name	City	State
Germany	Please Contact the Merck KGaA Communication Center	Darmstadt

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Maximum Observed Plasma Concentration (Cmax) of Evobrutinib		Pre-dose up to 30 hours post-dose
Secondary	Occurrences of Treatment-emergent Adverse Events (TEAEs)		Day 1 up to Day 6
Secondary	Number of Subjects With TEAEs According to Severity		Day 1 up to Day 6
Secondary	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
Secondary	Time to Reach the Maximum Plasma Concentration (tmax) of Evobrutinib		Pre-dose up to 30 hours post-dose
Secondary	Time Prior to the First Measurable (Non-Zero) Concentration (t lag) of Evobrutinib		Pre-dose up to 30 hours post-dose
Secondary	Terminal Rate Constant (?z) of Evobrutinib		Pre-dose up to 30 hours post-dose
Secondary	Terminal Half-Life (t1/2) of Evobrutinib		Pre-dose up to 30 hours post-dose
Secondary	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
Secondary	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
Secondary	Apparent Clearance (CL/f) of Evobrutinib		Pre-dose up to 30 hours post-dose
Secondary	Apparent Volume of Distribution During Terminal Phase (Vz/f) of Evobrutinib		Pre-dose up to 30 hours post-dose
Secondary	Amount of Unchanged Drug (Evobrutinib) Excreted in Urine During Collection Interval (0-8 hours) (Ae0-8h)		Pre-dose up to 8 hours post-dose
Secondary	Fraction of Administered Drug (Evobrutinib) Excreted in Urine (fe)		Pre-dose up to 30 hours post-dose
Secondary	Fraction of Unbound Drug (Evobrutinib) in the Plasma (fu)		Pre-dose up to 30 hours post-dose
Secondary	Renal Clearance of Evobrutinib (CLR)		Pre-dose up to 30 hours post-dose
Secondary	Non-Renal Clearance of Evobrutinib (CLNonR/f)		Pre-dose up to 30 hours post-dose