Enpatoran Human Mass Balance and Absolute Bioavailability Study

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Completed
• CT.gov ID: NCT05110027
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arms: 2
• Actual Duration (Months): 1.6
• Patients Per Site Per Month: 4.3

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Enpatoran; Drug: [14C]enpatoran microtracer; Drug: [14C]enpatoran microdose	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Nov 5, 2021
• Actual Primary Completion Date: Dec 24, 2021
• Actual Study Completion Date: Dec 24, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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

1. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRA Health Sciences	Groningen		Netherlands	9702

Sponsors and Collaborators

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

Investigators

• Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Trial Awareness and Transparency website

Publications

None provided.

• Responsible Party: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT05110027
• Other Study ID Numbers: MS200569_0040; 2021-004164-10
• First Posted: Nov 5, 2021
• Last Update Posted: Apr 4, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: Microtracer; Microdose; Clinical Pharmacology

Study Results

No Results Posted as of Apr 4, 2022