Enpatoran Human Mass Balance and Absolute Bioavailability Study

Healthy Clinical Trial

Official title:

Phase I, Open-Label, 2-Period, Single-Sequence Study to Evaluate the Mass Balance and Absorption, Disposition, Metabolism and Excretion of [14C]Enpatoran, and the Absolute Bioavailability of Enpatoran in Healthy Male Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05110027
• Other study ID #: MS200569_0040
• Secondary ID: 2021-004164-10
• Status: Completed
• Phase: Phase 1
• Start date: November 5, 2021
• Est. completion date: December 24, 2021

Study information

• Verified date: March 2022
• Source: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of Period 1 of this study is to provide a definitive quantitative characterization of the mass balance, and rates and routes of excretion of enpatoran, and to determine and quantify enpatoran and its metabolites in excreta (urine and feces) and plasma. The purpose of Period 2 of this study is to determine the absolute oral bioavailability of enpatoran. Total minimum duration of study participation for each participant is approximately 50 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: December 24, 2021
• Est. primary completion date: December 24, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring (blood pressure, heart rate and 12-lead electrocardiogram)

• Have a body weight within 50 to 110 kilogram (kg) and Body mass index (BMI) within the range = 18.0 and = 30.0 kilogram per meter square (kg/m^2)

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• History or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders

• Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to Screening

• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism and excretion (ADME) of drugs, or which may jeopardize the participant in case of participation in the study

• History of any malignancy

• History or presence of epilepsy, neurological disorders with seizure propensity or undiagnosed loss of consciousness, severe head trauma within 6 months or severe depression within 12 months prior to Screening), or neuropsychiatric conditions

• History of chronic or recurrent acute infection or any bacterial, viral, parasitic or fungal infections within 30 days prior to Screening and at any time between Screening and admission, or hospitalization due to infection within 6 months prior to Screening, or a history of herpes zoster within 12 months prior to Screening.

• History of drug hypersensitivity ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients; history of serious allergic reactions leading to hospitalization or any other hypersensitivity reaction in general, which may affect the safety of the participant and/or outcome of the study per the Investigator's discretion

• History of alcoholism or drug abuse within 1 year prior to Screening, or evidence of such abuse as indicated by the laboratory assays conducted during Screening

• Any condition, including findings in the laboratory tests, medical history, or other Screening assessments, that in the opinion of the Investigator constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study's objectives, conduct, or evaluation

• Other protocol defined exclusion criteria could apply

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Enpatoran
Participants will receive single oral dose of enpatoran tablet on Day 1
• [14C]enpatoran microtracer
Participants will receive single oral dose of non-labeled enpatoran solution spiked with microtracer of [14C]enpatoran on Day 1 of Period 1.
• [14C]enpatoran microdose
Participants will receive intravenous [14C]enpatoran microdose administered at 1.5 hours after the oral dose of enpatoran on Day 1 of Period 2.

Locations

Country	Name	City	State
Netherlands	PRA Health Sciences	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Period 1: Percent Urinary Recovery (feurine) of Total Radioactivity per Sampling Interval		-24-0 hours (pre-dose), 0-4, 4-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours after the initiation of the intravenous (IV) dose
Primary	Period 1: Percent Fecal Recovery (fefeces) of Total Radioactivity per Sampling Interval		-24-0 hours (pre-dose), 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours after the initiation of the intravenous (IV) dose
Primary	Period 1: Percent Total Recovery in Urine and Feces (fetotal) of Total Radioactivity per Sampling Interval		Urine: -24-0 hours (pre-dose), 0-4, 4-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours post-dose; Feces: -24-0 hours (pre-dose), 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours post-dose of IV injection
Primary	Period 1: Pharmacokinetic Plasma and Blood Concentration of Total Radioactivity		Pre-dose (Day 1), 15, 30 minutes, 1, 1.5, 2.0, 4.0, 6.0, 8.0, 12, 24, 48, 72, 96, 120, 144, 168 hours post-dose
Primary	Period 1: Pharmacokinetic Plasma Concentration of Enpatoran		Pre-dose (Day 1), 15, 30 minutes, 1, 1.5, 2.0, 4.0, 6.0, 8.0, 12, 24, 48, 72, 96, 120, 144, 168 hours post-dose
Primary	Period 2: Pharmacokinetic Plasma and Blood Concentration of [14C]Enpatoran and Enpatoran		[14C]Enpatoran: Pre-dose, 5, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose; Enpatoran: Pre-dose, 30 minutes, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose
Secondary	Period 1 and 2: Safety Profile as Assessed by Incidence of Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Laboratory Variables, Vital Signs and Electrocardiogram (ECG) Measurements		Period 1: Baseline up to Day 14; Period 2: Baseline up to Day 4

External Links

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