Enpatoran Human Mass Balance and Absolute Bioavailability Study

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Enpatoran; Drug: [14C]enpatoran microtracer; Drug: [14C]enpatoran microdose

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9702
    • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1: Enpatoran + [14C]enpatoran microtracer	Drug: Enpatoran; Participants will receive single oral dose of enpatoran tablet on Day 1; Drug: [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.
Experimental: Period 2: Enpatoran + [14C]enpatoran microdose	Drug: Enpatoran; Participants will receive single oral dose of enpatoran tablet on Day 1; Drug: [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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
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
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
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
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
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2021
• Primary Completion (Actual): December 24, 2021
• Study Completion (Actual): December 24, 2021

Study Registration Dates

• First Submitted: October 27, 2021
• First Submitted That Met QC Criteria: October 27, 2021
• First Posted (Actual): November 5, 2021

Study Record Updates

• Last Update Posted (Actual): April 4, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Microtracer; Microdose; Clinical Pharmacology
• Other Study ID Numbers: MS200569_0040; 2021-004164-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https:\\bit.ly/IPD21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No