This Study Tests How Healthy Men Tolerate Different Doses of BI 730357 and How the Metabolism of Midazolam is Affected by BI 730357

NCT03279978 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 1407-00022017-001653-14
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

Phase Ib evaluation of the safety, tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) properties of Multiple Rising Dose (MRD) administration of BI 730357 to healthy volunteers for up to 28 days.

Conditions

Healthy; Psoriasis

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Drug-related Adverse Events (AEs)

  Number of subjects with drug-related Adverse Events (AEs) assessed by the investigator.

  From first drug administration until 7 days after last dose, up to 21 days (for 25, 50 and 100 mg dose groups) and up to 35 days (for 200 and 400 mg dose groups)

Secondary Outcomes (4)

• Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1)

  -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h and 23.5h after first dosing on Day1.

• Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax)

  -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h and 23.5h after first dosing on Day1.

• Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration.

  Day 14 and Day 28 (Please refer description for the time frame in detail)

• Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss)

  Day 14 and Day 28 (Please refer description for the time frame in detail)

Study Arms (10)

BI 730357 25 mg fast

EXPERIMENTAL

Subjects were orally administered BI 730357 25 mg, film-coated tablet once daily over 14 days after a fasting period of at least 6 hours

Drug: BI 730357

Placebo fast

PLACEBO COMPARATOR

Subjects were orally administered matching Placebo to BI 730357, film-coated tablet after a fasting period of at least 6 hours.

Drug: Placebo

Placebo fed

PLACEBO COMPARATOR

Subjects were orally administered matching Placebo to BI 730357, film-coated tablet after the intake of a standard continental breakfast.

Drug: Placebo

BI 730357 50 mg fast

EXPERIMENTAL

Subjects were orally administered BI 730357 50 mg, film-coated tablet once daily over 14 days after a fasting period of at least 6 hours.

Drug: BI 730357

BI 730357 50mg/Placebo

EXPERIMENTAL

Subject was orally administered mixed treatment of BI 730357 50 mg and placebo, film-coated tablet once daily over 14 days after a fasting period of at least 6 hours

Drug: BI 730357; Drug: Placebo

BI 730357 50 mg fed

EXPERIMENTAL

Subjects were orally administered BI 730357 50 mg, film-coated tablet once daily over 14 days after the intake of a standard continental breakfast.

Drug: BI 730357

BI 730357 100 mg fast

EXPERIMENTAL

Subjects were orally administered BI 730357 100 mg, film-coated tablet once daily over 14 days after a fasting period of at least 6 hours

Drug: BI 730357

BI 730357 200 mg fast

EXPERIMENTAL

Subjects were orally administered BI 730357 200 mg, film-coated tablet once daily over 28 days after a fasting period of at least 6 hours

Drug: BI 730357

BI 730357 200 mg fed

EXPERIMENTAL

Subjects were orally administered a microdose of midazolam 75 microgram (75 μg) solution for injection, orally on Day -1, and prior receiving BI 730357 on Days 3, and 14. Subjects were orally administered BI 730357 200 mg, film-coated tablet once daily over 28 days after the intake of a standard continental breakfast.

Drug: BI 730357; Drug: Midazolam

BI 730357 400 mg fed

EXPERIMENTAL

Subjects were orally administered a microdose of midazolam 75 microgram (75 μg) solution for injection, orally on Day -1, and prior receiving BI 730357 on Days 3, and 14. Subjects were orally administered BI 730357 400 mg, film-coated tablet once daily over 28 days after the intake of a standard continental breakfast.

Drug: BI 730357; Drug: Midazolam

Interventions

BI 730357 DRUG

BI 730357 film-coated tablet

BI 730357 100 mg fast; BI 730357 200 mg fast; BI 730357 200 mg fed; BI 730357 25 mg fast; BI 730357 400 mg fed; BI 730357 50 mg fast; BI 730357 50 mg fed; BI 730357 50mg/Placebo

Placebo DRUG

Placebo

BI 730357 50mg/Placebo; Placebo fast; Placebo fed

Midazolam DRUG

Once per day (QD) on Days -1, 3, and 14. Dose groups BI 730357 200 mg fed and BI 730357 400 mg fed

BI 730357 200 mg fed; BI 730357 400 mg fed

Eligibility Criteria

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

You may qualify if:

• Healthy male subjects according to the assessment of the Investigator, based on a complete medical history, physical examination, vital signs (blood pressure, pulse rate), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
• Subjects with a partner who is a woman of childbearing potential (WOCBP) must be willing to use male contraception (condom or sexual abstinence) from the first administration of trial medication until 30 days after last administration of trial medication
• Age of 18 to 45 years (incl.) at screening
• Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.) at screening
• Signed and dated written informed consent prior to admission to the study in accordance with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation

You may not qualify if:

• Any finding in the medical examination (including blood pressure, pulse rate or Electrocardiogram (ECG)) deviating from normal and judged as clinically relevant by the Investigator
• Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (bpm)
• Any laboratory value outside the reference range that the Investigator considers to be of clinical relevance
• Any evidence of a concomitant disease judged as clinically relevant by the Investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Cholecystectomy and/or surgery of the gastrointestinal tract (except appendectomy and simple hernia repair) that could interfere with the PK of the trial medication
• Diseases of the Central Nervous System (CNS) (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• Chronic or acute infections which are of relevance in the opinion of the Investigator
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
• Use of drugs within 30 days prior to administration of trial medication if that might reasonably influence the results of the trial (incl. QT/QTc (corrected QT interval) interval prolongation)
• Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug
• Tobacco usage (more than 10 cigarettes or 3 cigars or 3 pipes per day)
• Alcohol abuse (consumption of more than 30 g per day)
• Drug abuse or positive drug screening

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

CTC North GmbH & Co. KG, Hamburg

Hamburg, 20251, Germany

Location

Related Publications (1)

• Ooi QX, Kristoffersson A, Korell J, Flack M, L Plan E, Weber B. Bounded integer model-based analysis of psoriasis area and severity index in patients with moderate-to-severe plaque psoriasis receiving BI 730357. CPT Pharmacometrics Syst Pharmacol. 2023 Jun;12(6):758-769. doi: 10.1002/psp4.12948. Epub 2023 May 1.

  PMID: 36919398 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Psoriasis

Interventions

Midazolam

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 12, 2017
• Study Start: January 9, 2018
• Primary Completion: August 24, 2018
• Study Completion: August 30, 2018
• Last Updated: December 19, 2024
• Results First Posted: September 21, 2023

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)