Study Comparing Pharmacokinetics of Different Formulations of Evobrutinib in Healthy Participants

Healthy Clinical Trial

Official title:

A Phase I, Single-site, Open-label, Partially Randomized Study to Evaluate the Relative Bioavailability and Pharmacokinetics of Evobrutinib Following Administration of Different Formulations in Healthy Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05245396
• Other study ID #: MS200527_0091
• Secondary ID: 2021-005056-11
• Status: Completed
• Phase: Phase 1
• Start date: February 2, 2022
• Est. completion date: February 14, 2023

Study information

• Verified date: March 2023
• 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 this study is to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety and tolerability of evobrutinib after oral administration of immediate release (IR) and modified release (MR) formulations in healthy participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: February 14, 2023
• Est. primary completion date: February 14, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Participants are overtly healthy as determined by medical evaluation, including comprehensive clinical assessment (detailed medical history and a complete physical examination), ECG, and laboratory investigations (hematology and biochemistry)

• Participants have a body weight within 50.0 to 100.0 kilogram (kg) and body mass index (BMI) within the range 19 to 32 kilogram per meter square (kg/m^2) (inclusive)

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Participants with history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, metabolic, hematological, lymphatic, neurological (including epilepsy), cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, as determined by medical evaluation

• Participants with history of any malignancy

• Administration of live vaccines or live-attenuated virus vaccines within 3 months prior to Screening. Administration of other types of vaccines (e.g. SARS-CoV-2 vaccines) is allowed until 2 weeks before the admission to the CRU

• Medical history and physical examination results that include any ongoing clinically relevant findings as judged by the Investigator

• Moderate or strong inhibitors or inducers of CYP3A4/5 or Pgp within 4 weeks prior to the first administration of study intervention

• Other protocol-defined exclusion criteria could apply

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Ref (TF2)
Participants will receive 2 single oral doses of Ref (TF2) on Day 1 in treatment period 1, 2, or 3 of Part A, B, C and D.
• Evobrutinib MR-T1
Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.
• Evobrutinib MR-T2
Participants will receive single oral dose of MR-T2 on Day 1 in treatment period 1, 2, and 3 of Part A.
• Evobrutinib MR-T3
Participants will receive single oral dose of MR-T3 on Day 1 in treatment period 1, 2, and 3 of Part A.
• Evobrutinib MR-T4
Participants will receive single oral dose of MR-T4 on Day 1 in treatment period 1, 2, and 3 of Part A.
• Evobrutinib MUPS-C1
Participants will receive single oral dose of MUPS-C1 on Day 1 in treatment period 1, 2, and 3 of Part B.
• Evobrutinib MUPS-C2
Participants will receive single oral dose of MUPS-C2 on Day 1 in treatment period 1, 2, and 3 of Part B.
• Evobrutinib MUPS-C3
Participants will receive single oral dose of MUPS-C3 on Day 1 in treatment period 1, 2, and 3 of Part C.
• Evobrutinib MUPS-C4
Participants will receive single oral dose of MUPS-C4 on Day 1 in treatment period 1, 2, and 3 of Part C.
• Evobrutinib MR-T adapated
Participants will receive single oral dose of MR-T adapted on Day 1 in treatment period 1, 2, and 3 of Part D.

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical Ltd	Nottingham

Sponsors (2)

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

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero to 24 Hours Post Dose [Frel(AUC0-24)] of Evobrutinib Modified-Release Formulation Compared to Immediate-Release Evobrutinib Reference Formulation		Pre-dose up to 72 hours post-dose on Day 4
Primary	Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero to Infinity [Frel(AUC0-inf)] of Evobrutinib Modified-Release Formulation Compared to Immediate-Release Evobrutinib Reference Formulation		Pre-dose up to 72 hours post-dose on Day 4
Secondary	Number of Participants with Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Abnormal Laboratory Test Results, Abnormal Vital Signs and Abnormal Electrocardiogram (ECG) Measurements		Up to Day 123
Secondary	Pharmacokinetic Plasma Concentration of Evobrutinib Formulations		Pre-dose up to 72 hours post-dose on Day 4

External Links

•   Trial Awareness and Transparency website