Effect of Food on Peposertib PK

Study Overview
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Brief Summary
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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.

Official Title
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Phase I, Open-Label, Randomized, Single-Dose Study With Crossover Design to Investigate the Effect of Food on the PK of Peposertib Tablet Formulation and to Investigate the PK of Peposertib Administered as Oral Suspension of Disintegrated Tablets

Conditions
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Healthy

Intervention / Treatment
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* Drug: Peposertib
* Drug: Peposertib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Other protocol defined inclusion criteria could apply Exclusion Criteria: 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. Other protocol defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Peposertib: Treatment Sequence A-B-C<br>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<br>* Participants will receive single oral dose of Peposertib tablet under fasting (Treatment A) or fed (Treatment B) conditions.<br>* Other names: M3814;Drug: Peposertib<br>* Participants will receive oral suspension dose of peposertib tablets under fasted condition (Treatment C) in either period 1, 2 or 3 of part 1.<br>* Other names: M3814;|
| Experimental: Part 1: Peposertib Treatment Sequence A-C-B<br>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<br>* Participants will receive single oral dose of Peposertib tablet under fasting (Treatment A) or fed (Treatment B) conditions.<br>* Other names: M3814;Drug: Peposertib<br>* Participants will receive oral suspension dose of peposertib tablets under fasted condition (Treatment C) in either period 1, 2 or 3 of part 1.<br>* Other names: M3814;|
| Experimental: Part 1: Peposertib Treatment Sequence B-A-C<br>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<br>* Participants will receive single oral dose of Peposertib tablet under fasting (Treatment A) or fed (Treatment B) conditions.<br>* Other names: M3814;Drug: Peposertib<br>* Participants will receive oral suspension dose of peposertib tablets under fasted condition (Treatment C) in either period 1, 2 or 3 of part 1.<br>* Other names: M3814;|
| Experimental: Part 1: Peposertib Treatment Sequence B-C-A<br>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<br>* Participants will receive single oral dose of Peposertib tablet under fasting (Treatment A) or fed (Treatment B) conditions.<br>* Other names: M3814;Drug: Peposertib<br>* Participants will receive oral suspension dose of peposertib tablets under fasted condition (Treatment C) in either period 1, 2 or 3 of part 1.<br>* Other names: M3814;|
| Experimental: Part 1: Peposertib: Treatment Sequence C-A-B<br>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<br>* Participants will receive single oral dose of Peposertib tablet under fasting (Treatment A) or fed (Treatment B) conditions.<br>* Other names: M3814;Drug: Peposertib<br>* Participants will receive oral suspension dose of peposertib tablets under fasted condition (Treatment C) in either period 1, 2 or 3 of part 1.<br>* Other names: M3814;|
| Experimental: Part 1: Peposertib Treatment Sequence C-B-A<br>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<br>* Participants will receive single oral dose of Peposertib tablet under fasting (Treatment A) or fed (Treatment B) conditions.<br>* Other names: M3814;Drug: Peposertib<br>* Participants will receive oral suspension dose of peposertib tablets under fasted condition (Treatment C) in either period 1, 2 or 3 of part 1.<br>* Other names: M3814;|
| Experimental: Part 2: Peposertib Treatment Sequence A-B<br>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<br>* Participants will receive single oral dose of Peposertib tablet under fasting (Treatment A) or fed (Treatment B) conditions.<br>* Other names: M3814;|
| Experimental: Part 2: Peposertib: Treatment Sequence B-A<br>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<br>* Participants will receive single oral dose of Peposertib tablet under fasting (Treatment A) or fed (Treatment B) conditions.<br>* Other names: M3814;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Number of participants with clinically significant change from baseline in laboratory parameters, vital signs and 12-Lead electrocardiogram (ECG) findings will be reported. | Part 1: up to 21 days; Part 2: up to 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peposertib, Pharmacokinetics, Relative Bioavailability