CompletedNCT03297983Updated Jul 23, 2018

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

A Phase 1 interventional study of M7583 in Healthy, sponsored by Merck KGaA, Darmstadt, Germany. Completed at 1 site in Germany. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-07-23.

Sponsored by Merck KGaA, Darmstadt, Germany · Phase 1, Interventional, and Other

Phase: Phase 1
Study type: Interventional
Enrollment: 18
Allocation: Randomized
Ages: 18 Years to 55 Years
Sex: All

Study 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 studied

Healthy

Keywords

M7583
Healthy Subjects
Cross-over

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

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.

Exclusion criteria

Exclusion Criteria:

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.
12-Lead ECG showing a QTcF > 450 ms, PQ > 200ms, or QRS > 120 ms or other clinically relevant abnormal findings

Study design

Phase: Phase 1
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 18 participants (actual)

Study arms

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

Interventions

DrugM7583
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.

What researchers measure

Primary outcomes

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

Occurrence of Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: 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
Time frame: Up to Week 6
Number of Subjects with Clinically Significant Change From Baseline in Laboratory Tests, Vital Sign and 12-lead Electrocardiogram (ECG) Findings
Time frame: Up to Week 6
Time to Reach the Maximum Plasma Concentration (tmax) of M7583
Time frame: 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
Time frame: 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
Apparent Terminal Half-life (t1/2) of M7583
Time frame: 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
Total Body Clearance of Drug From Plasma Following Oral Administration (CL/f) of M7583
Time frame: 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
Apparent Volume of Distribution (Vz/f) of M7583
Time frame: 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 M7583 Plasma Concentration-time Curve From Time Zero to 24 hours After Dosing (AUC0-24h)
Time frame: 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
Percentage of AUC0-∞ Obtained by Extrapolation (%AUCextra) of M7583
Time frame: 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
Relative Bioavailability of M7583 Tablet versus M7583 PIC (Frel,T/P)
Time frame: 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
Relative Bioavailability of M7583 Tablet Administered 30 Minutes After a Standard Breakfast Versus Tablet Administered After an Overnight Fast (Frel,Fed/Fasted)
Time frame: 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 locations

1 site

Nuvisan GmbH
Neu-Ulm, Bavaria 89231, Germany

Registry details

Key details

Study ID: NCT03297983
Lead sponsor: Merck KGaA, Darmstadt, Germany
Responsible party: Sponsor
First posted: Sep 29, 2017
Start date: Oct 9, 2017
Primary completion: Dec 6, 2017
Completion: Dec 6, 2017
Last update: Jul 23, 2018

Study contacts

Medical Responsible

study director · Merck KGaA, Darmstadt, Germany

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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