M7583 Relative Bioavailability of Tablet Compared to Powder-in-capsule

NCT03297983 | Completed Phase 1

• 2 other identifiers: MS200662-00172017-001674-41
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I study consisting of 2 parts: Part 1 aims to investigate the relative bioavailability of tablet formulation (test treatment) and Powder in capsule (PiC) formulation (reference treatment) of M7583 under fasted conditions. The aim of Part 2 is to determine and compare the single dose Pharmacokinetic (PK) profile of M7583 tablet under fasted and fed conditions to assess the food effect.

Conditions

Healthy

Keywords

M7583; Healthy Subjects; Cross-over

Outcome Measures

Primary Outcomes (3)

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concnetration (AUC0-t) of M7583

  pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period

• Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of M7583

  pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period

• Maximum Observed Drug Concentration (Cmax) of M7583

  pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period

Secondary Outcomes (12)

• Occurrence of Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

  Up to Week 6

• Occurrence of Subjects With TEAEs by Severity According to Qualitative Toxicity Scale Selected From National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  Up to Week 6

• Number of Subjects with Clinically Significant Change From Baseline in Laboratory Tests, Vital Sign and 12-lead Electrocardiogram (ECG) Findings

  Up to Week 6

• Time to Reach the Maximum Plasma Concentration (tmax) of M7583

  pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period

• Terminal Rate Constant (λz) of M7583

  pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period

Study Arms (2)

First M7583 Tablet:Fasted, Then PiC:Fasted, Then Tablet:Fed

EXPERIMENTAL

Drug: M7583

First M7583 PiC:Fasted, Then Tablet:Fasted, Then Tablet:Fed

EXPERIMENTAL

Drug: M7583

Interventions

M7583 DRUG

Subject will receive either M7583 PiC or M7583 tablet formulation orally under fasted conditions in part 1 followed by M7583 tablet formulation under fed condition in part 2 of the study.

First M7583 PiC:Fasted, Then Tablet:Fasted, Then Tablet:Fed; First M7583 Tablet:Fasted, Then PiC:Fasted, Then Tablet:Fed

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adult males and females between 18 and 55 years of age (inclusive) with total body weight between 50.0 and 100.0 kilogram (kg) (inclusive) and body mass index (BMI) between 19.0 and 30.0 kilogram per meter square (kg/m2) (inclusive) at the time of the Screening examination.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding.
• Females must have a negative serum pregnancy test at Screening visit and at Day -1 before randomization/first dosing.
• Men must agree to use a barrier method (specifically, male condom with or without spermicide) and to have their female partners use a highly effective method of contraception during the treatment period, and for at least 3 months after the last IMP administration. Men must also refrain from donating sperm during this period.
• Healthy as assessed by the Investigator with no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection or disease that would pose a risk to subject safety or interfere with the trial evaluation, procedures, or completion.
• Stable non-smokers for at least 3 months preceding Screening.
• Must agree not to consume any alcohol during the treatment period of the trial.
• Able and willing to give written informed consent and has signed the appropriate written informed consent form, approved by the Investigator's Independent Ethics Committee (IEC), prior to the performance of any trial activities.

You may not qualify if:

• History of clinically relevant disease of any organ system, that may interfere with the objectives of the trial or provide a risk to the health of the subject.
• 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.
• 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 subject and/or outcome of the trial per the Investigator's discretion.
• History of alcoholism or drug abuse within 2 years prior to Screening and the subject is unwilling to abstain from alcohol and drug of abuse during the trial
• Consumption of an average weekly intake of greater than (\>) 14 drinks/week for males or \> 7 drinks/week for females. One drink is equivalent to (12 g alcohol) = 5 ounces (150 milliliter (mL)) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of 40 Vol% distilled spirits.
• Positive for drugs of abuse, nicotine/cotinine or alcohol at Screening or at admission.
• Supine systolic blood pressure \> 140 mmHg or less than (\<) 90 mmHg, diastolic blood pressure \> 90 mmHg or \<50 and pulse rate \>100 or ≤ 50 bpm, at admission.
• Lead ECG showing a QTcF \> 450 ms, PQ \> 200ms, or QRS \> 120 ms or other clinically relevant abnormal findings

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Nuvisan GmbH

Neu-Ulm, Bavaria, 89231, Germany

Location

Study Officials

• Medical Responsible

  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: September 27, 2017
• First Posted: September 29, 2017
• Study Start: October 9, 2017
• Primary Completion: December 6, 2017
• Study Completion: December 6, 2017
• Last Updated: July 23, 2018

Record last verified: 2018-07

Locations

DE (1)