Effect of Renal Impairment on Evobrutinib Pharmacokinetics (PK)

NCT03436394 | Completed Phase 1

• 2 other identifiers: MS200527_00262017-004102-18
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Impairment

Keywords

Renal Impairment; Evobrutinib; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (16)

• 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

  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

Study Arms (4)

Evobrutinib: Normal Renal Function

EXPERIMENTAL

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

Evobrutinib: Severe Renal Impairment

EXPERIMENTAL

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

Evobrutinib: Moderate Renal Impairment

EXPERIMENTAL

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

Evobrutinib: Mild Renal Impairment

EXPERIMENTAL

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

Evobrutinib DRUG

Subjects will be administered a single oral dose of evobrutinib under fasting conditions.

Also known as: MSC2364447C, M2951

Evobrutinib: Mild Renal Impairment; Evobrutinib: Moderate Renal Impairment; Evobrutinib: Normal Renal Function; Evobrutinib: Severe Renal Impairment

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Please Contact the Merck KGaA Communication Center

Darmstadt, 64293, Germany

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

evobrutinib

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2018
• First Posted: February 19, 2018
• Study Start: March 21, 2018
• Primary Completion: February 22, 2019
• Study Completion: February 22, 2019
• Last Updated: May 16, 2019

Record last verified: 2019-05

Locations

DE (1)