Renal ImpairmentPhase 1NCT03436394
Effect of Renal Impairment on Evobrutinib Pharmacokinetics (PK)
A Phase 1 study testing Evobrutinib in people with Renal Impairment, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Renal Impairment
- What is being tested?
- Evobrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteGermany
- Study dates
- 21 Mar 2018to 22 Feb 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Please Contact the Merck KGaA Communication Center
Darmstadt, 64293
About this study
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
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
- Being tested
- Evobrutinib
- Keywords
- Renal Impairment, Evobrutinib, Pharmacokinetics
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvobrutinibDrug
Also called MSC2364447C, M2951
Subjects will be administered a single oral dose of evobrutinib under fasting conditions.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Evobrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Evobrutinib
Measured: 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
Measured: Pre-dose up to 30 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib
Measured: Pre-dose up to 30 hours post-dose
Secondary outcomes (16)
Occurrences of Treatment-emergent Adverse Events (TEAEs)
Measured: Day 1 up to Day 6
Number of Subjects With TEAEs According to Severity
Measured: 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.
Measured: Day 1 up to Day 6
Time to Reach the Maximum Plasma Concentration (tmax) of Evobrutinib
Measured: Pre-dose up to 30 hours post-dose
Time Prior to the First Measurable (Non-Zero) Concentration (t lag) of Evobrutinib
Measured: Pre-dose up to 30 hours post-dose
Terminal Rate Constant (λz) of Evobrutinib
Measured: Pre-dose up to 30 hours post-dose
Terminal Half-Life (t1/2) of Evobrutinib
Measured: 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
Measured: 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
Measured: Pre-dose up to 8 hours post-dose
Apparent Clearance (CL/f) of Evobrutinib
Measured: Pre-dose up to 30 hours post-dose
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Evobrutinib
Measured: Pre-dose up to 30 hours post-dose
Amount of Unchanged Drug (Evobrutinib) Excreted in Urine During Collection Interval (0-8 hours) (Ae0-8h)
Measured: Pre-dose up to 8 hours post-dose
Fraction of Administered Drug (Evobrutinib) Excreted in Urine (fe)
Measured: Pre-dose up to 30 hours post-dose
Fraction of Unbound Drug (Evobrutinib) in the Plasma (fu)
Measured: Pre-dose up to 30 hours post-dose
Renal Clearance of Evobrutinib (CLR)
Measured: Pre-dose up to 30 hours post-dose
Non-Renal Clearance of Evobrutinib (CLNonR/f)
Measured: Pre-dose up to 30 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start21 Mar 2018
- Primary completion22 Feb 2019
- Study completion22 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03436394
- Sponsor's protocol ID
- MS200527_0026
- Other IDs
- 2017-004102-18, 2017
- Status last verified
- May 2019
- First submitted
- 6 Feb 2018
- Last updated
- 16 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03436394
- Acronym / sponsor ID
- MS200527_0026
- Conditions
- Renal Impairment
- Keywords
- Renal Impairment, Evobrutinib, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 21 Mar 2018 (actual)
- Primary completion
- 22 Feb 2019 (actual)
- Study completion
- 22 Feb 2019 (actual)
- First posted
- 19 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Evobrutinib: Normal Renal Function | Experimental | Drug: EvobrutinibSubjects 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. |
| Evobrutinib: Severe Renal Impairment | Experimental | Drug: EvobrutinibSubjects with eGFR less than (<) 30 mL/min/1.73 m^2 will receive a single oral dose of evobrutinib under fasting conditions. |
| Evobrutinib: Moderate Renal Impairment | Experimental | Drug: EvobrutinibSubjects 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. |
| Evobrutinib: Mild Renal Impairment | Experimental | Drug: EvobrutinibSubjects 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. |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvobrutinibAlso: MSC2364447C, M2951Subjects will be administered a single oral dose of evobrutinib under fasting conditions. | Drug | Evobrutinib: Mild Renal Impairment, Evobrutinib: Moderate Renal Impairment, Evobrutinib: Normal Renal Function, Evobrutinib: Severe Renal Impairment |
Primary outcome
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
16 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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Evobrutinib in people with Renal Impairment, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2019.