Effect of Food on Peposertib PK

NCT04702698 | Completed Phase 1

• 2 other identifiers: MS100036_00402020-004187-26
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The study will investigate the effect of food on the Pharmacokinetic (PK) of a single dose of peposertib administered as film-coated tablet under fed and fasted conditions. Furthermore, the PK profile of peposertib administered as an oral suspension of disintegrated tablets and as film-coated tablets will be compared under fasted conditions to evaluate the relative bioavailability in healthy participants.

Conditions

Healthy

Keywords

Peposertib; Pharmacokinetics; Relative Bioavailability

Outcome Measures

Primary Outcomes (3)

• Part 1 and Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Sampling (AUC0-tlast) of Peposertib

  Pre-dose up to 36 hours post-dose

• Part 1 and Part 2: Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC-inf) of Peposertib

  Pre-dose up to 36 hours post-dose

• Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) of Peposertib

  Pre-dose up to 36 hours post-dose

Secondary Outcomes (3)

• Part 1 and Part 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

  Part 1: up to 21 days; Part 2: up to 14 days

• Part 1 and Part 2: Number of Participants With Treatment -Emergent Adverse Events (TEAEs) Based on Severity According to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

  Part 1: up to 21 days; Part 2: up to 14 days

• Part 1 and Part 2: Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters, Vital Signs and 12-Lead Electrocardiogram (ECG) Findings

  Part 1: up to 21 days; Part 2: up to 14 days

Study Arms (8)

Part 1: Peposertib: Treatment Sequence A-B-C

EXPERIMENTAL

Participants will receive single oral dose of peposertib tablet (Treatment A) on Day 1 under fasted condition in period 1, followed by single oral dose of peposertib tablet (Treatment B) on Day 8 under fed condition in period 2, followed by oral suspension dose of peposertib (Treatment C) on Day 15 under fasted condition in period 3. There will be washout period of 7 days between each treatment period.

Drug: Peposertib

Part 1: Peposertib Treatment Sequence A-C-B

EXPERIMENTAL

Participants will receive single oral dose of peposertib tablet (Treatment A) on Day 1 under fasted condition in period 1, followed by oral suspension dose of peposertib (Treatment C) on Day 8 under fasted condition in period 2, followed by single oral dose of peposertib tablet (Treatment B) on Day 15 under fed condition in period 3. There will be washout period of 7 days between each treatment period.

Drug: Peposertib

Part 1: Peposertib Treatment Sequence B-A-C

EXPERIMENTAL

Participants will receive single oral dose of peposertib tablet (Treatment B) on Day 1 under fed condition in period 1, followed by single oral dose of peposertib tablet (Treatment A) on Day 8 under fasted condition in period 2, followed by oral suspension dose of peposertib (Treatment C) on Day 15 under fasted condition in period 3. There will be washout period of 7 days between each treatment period.

Drug: Peposertib

Part 1: Peposertib Treatment Sequence B-C-A

EXPERIMENTAL

Participants will receive single oral dose of peposertib tablet (Treatment B) on Day 1 under fed condition in period 1, followed by oral suspension dose of peposertib (Treatment C) on Day 8 under fasted condition in period 2, followed by single oral dose of peposertib tablet (Treatment A) on Day 15 under fasted condition in period 3. There will be washout period of 7 days between each treatment period.

Drug: Peposertib

Part 1: Peposertib: Treatment Sequence C-A-B

EXPERIMENTAL

Participants will receive oral suspension dose of peposertib (Treatment C) on Day 1 under fasted condition in period 1, followed by single oral dose of peposertib tablet (Treatment A) on Day 8 under fasted condition in period 2, followed by single oral dose of peposertib tablet (Treatment B) on Day 15 under fed condition in period 3. There will be washout period of 7 days between each treatment period.

Drug: Peposertib

Part 1: Peposertib Treatment Sequence C-B-A

EXPERIMENTAL

Participants will receive oral suspension dose of peposertib (Treatment C) on Day 1 under fasted condition in period 1, followed by single oral dose of peposertib tablet (Treatment B) on Day 8 under fed condition in period 2, followed by single oral dose of peposertib tablet (Treatment A) on Day 15 under fasted condition in period 3. There will be washout period of 7 days between each treatment period.

Drug: Peposertib

Part 2: Peposertib Treatment Sequence A-B

EXPERIMENTAL

Participants will receive single oral dose of peposertib tablet (Treatment A) on Day 1 under fasted condition in period 1, followed by single oral dose of peposertib tablet (Treatment B) on Day 8 under fed condition in period 2. There will be washout period of 7 days between each treatment period.

Drug: Peposertib

Part 2: Peposertib: Treatment Sequence B-A

EXPERIMENTAL

Participants will receive single oral dose of peposertib tablet (Treatment B) on Day 1 under fed condition in period 1, followed by single oral dose of peposertib tablet (Treatment A) on Day 8 under fasted condition in period 2. There will be washout period of 7 days between each treatment period.

Drug: Peposertib

Interventions

Peposertib DRUG

Participants will receive single oral dose of Peposertib tablet under fasting (Treatment A) or fed (Treatment B) conditions.

Also known as: MSC2490484A, M3814

Part 1: Peposertib Treatment Sequence A-C-B; Part 1: Peposertib Treatment Sequence B-A-C; Part 1: Peposertib Treatment Sequence B-C-A; Part 1: Peposertib Treatment Sequence C-B-A; Part 1: Peposertib: Treatment Sequence A-B-C; Part 1: Peposertib: Treatment Sequence C-A-B; Part 2: Peposertib Treatment Sequence A-B; Part 2: Peposertib: Treatment Sequence B-A

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring
• Participants are nonsmoker for at least 6 months prior to Screening
• Participants have a body weight greater than 50 kilogram (kg) and a body mass index within the range 18.5 to 30.0 kilogram per meter square (inclusive) at Screening
• Male participants are refrain from donating sperm plus either abstain from any activity that allows for exposure to ejaculate
• Female participants are not pregnant or breastfeeding

You may not qualify if:

• History of clinically relevant renal, cardiovascular, pulmonary disease, or endocrinology disorder at Screening
• History of clinically relevant gastrointestinal disease, in particular pancreatic disease, cholecystitis, liver diseases or hepatic dysfunction at Screening
• History of psychiatric or relevant neurological disorders (example, depression, epilepsy) at Screening
• History of relevant skin and mucosal diseases (rash, mucositis) at Screening
• Presence or history of any serious allergy (requiring hospitalization or prolonged systemic treatment) at Screening
• Any planned radiologic assessments during the study conduct phase
• Participants who are not able or willing to eat the entire study meals.

Sponsors & Collaborators

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

Study Sites (2)

Nuvisan GmbH

Gauting, Germany

Location

Nuvisan GmbH

Neu-Ulm, Germany

Location

Related Publications (1)

• Becker A, Krebs-Brown A, Vetter C, Reuter T, Rodriguez-Gutierrez A, You X, Lissy M. Phase I crossover study of DNA-protein kinase inhibitor peposertib in healthy volunteers: Effect of food and pharmacokinetics of an oral suspension. Clin Transl Sci. 2023 Dec;16(12):2628-2639. doi: 10.1111/cts.13657. Epub 2023 Oct 31.

  PMID: 37905356 DERIVED

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Interventions

peposertib

Study Officials

• Medical Responsible

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 11, 2021
• Study Start: January 14, 2021
• Primary Completion: March 3, 2021
• Study Completion: March 3, 2021
• Last Updated: May 12, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)