CompletedNCT03436394Updated May 16, 2019

Effect of Renal Impairment on Evobrutinib Pharmacokinetics (PK)

A Phase 1 interventional study of Evobrutinib in Renal Impairment, sponsored by Merck KGaA, Darmstadt, Germany. Completed at 1 site in Germany. Open to participants aged 18 Years to 79 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-05-16.

Sponsored by Merck KGaA, Darmstadt, Germany · Phase 1, Interventional, and Other

Phase: Phase 1
Study type: Interventional
Enrollment: 31
Allocation: Non-randomized
Ages: 18 Years to 79 Years
Sex: All

Study 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.

Conditions studied

Renal Impairment

Browse trials for

Renal Insufficiency 1,989

Keywords

Renal Impairment
Evobrutinib
Pharmacokinetics

Who can participate

Ages eligible: 18 Years to 79 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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 design

Phase: Phase 1
Primary purpose: Other
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 31 participants (actual)

Study arms

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
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
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
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

Interventions

DrugEvobrutinib
Subjects will be administered a single oral dose of evobrutinib under fasting conditions.
Also known as: MSC2364447C, M2951

What researchers measure

Primary outcomes

Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Evobrutinib
Time frame: 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
Time frame: Pre-dose up to 30 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib
Time frame: Pre-dose up to 30 hours post-dose

Secondary outcomes

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

Study locations

1 site

Please Contact the Merck KGaA Communication Center
Darmstadt, 64293, Germany

Registry details

Key details

Study ID: NCT03436394
Lead sponsor: Merck KGaA, Darmstadt, Germany
Responsible party: Sponsor
First posted: Feb 19, 2018
Start date: Mar 21, 2018
Primary completion: Feb 22, 2019
Completion: Feb 22, 2019
Last update: May 16, 2019

Study contacts

Medical Responsible

study director · Merck KGaA, Darmstadt, Germany

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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