A Study in Healthy Men and Women Who Are Either Between 18 - 45 Years or Between 65 - 80 Years to Test How Different Doses of BI 474121 Are Tolerated

NCT04537897 | Completed Phase 1 Results

• 2 other identifiers: 1411-00022020-001003-17
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The main objectives of this trial are to investigate safety and tolerability of BI 474121 in healthy male and female young and elderly subjects following oral administration of multiple rising doses per day over 14 days.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Drug-related Adverse Events

  Percentage of participants with drug-related adverse events is reported. Medical judgment were used to determine the relationship between study medication and the adverse events, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history.

  For Midazolam: From first dose of midazolam (on Day -1) until first dose of BI 474121/Placebo, up to 1 day. Other groups: From first dose of BI 474121/Placebo until last dose+7 days of residual effect period, up to 21 days.

Secondary Outcomes (10)

• Area Under the Concentration-time Curve of BI 474121 in Plasma From 0 to 24h (AUC0-24) After First Dose

  Within 1 hour (h) before and at 15 minutes (min), 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 23h45min after first dose of BI 474121.

• Maximum Measured Concentration of BI 474121 in Plasma (Cmax) After First Dose

  Within 1 hour (h) before and at 15 minutes (min), 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 23h45min after first dose of BI 474121.

• Area Under the Concentration-time Curve of BI 474121 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss)

  Within 15 minutes (min) before and at 15 min, 30min, 1hour (h), 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h after administration of BI 474121 on Day 14.

• Maximum Measured Concentration of BI 474121 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)

  Within 15 minutes (min) before and at 15 min, 30min, 1hour (h), 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h after administration of BI 474121 on Day 14.

• Maximum Measured Concentration of Midazolam in Plasma (Cmax) - Day -1

  Within 1 hour (h) 30 minutes (min) before and at 15min, 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 23h after the administration of Midazolam on Day -1.

Study Arms (9)

BI 474121 2.5mg (Part A)

EXPERIMENTAL

Young participants administered 1 tablet of 2.5 milligrams (mg) BI 474121 orally once daily over a treatment period of 14 days. On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily.

Drug: BI 474121; Drug: Midazolam

BI 474121 5mg (Part A)

EXPERIMENTAL

Young participants administered 2 tablets of 2.5 mg BI 474121 orally once daily (daily dose: 5 mg) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.

Drug: BI 474121

BI 474121 10mg (Part A)

EXPERIMENTAL

Young participants administered 1 tablet of 10 milligrams (mg) BI 474121 orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days. On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h).

Drug: BI 474121; Drug: Midazolam

BI 474121 20mg (Part A)

EXPERIMENTAL

Young participants administered 2 tablets of 10 milligrams (mg) BI 474121 orally once daily (daily dose: 20 mg) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days. On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h).

Drug: BI 474121; Drug: Midazolam

BI 474121 30mg (Part A)

EXPERIMENTAL

Young participants administered 3 tablets of 10 milligrams (mg) BI 474121 orally once daily (daily dose: 30 mg) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days. On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h).

Drug: BI 474121; Drug: Midazolam

Placebo (Part A)

PLACEBO COMPARATOR

Young participants administered matching placebo to part A once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days. On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) for placebo participants matched to 2.5mg BI, 10mg BI, 20mg BI, and 30mg BI groups.

Drug: BI 474121; Drug: Midazolam; Drug: Placebo

Placebo (Part B)

PLACEBO COMPARATOR

Elderly participants administered matching placebo to part B once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days

Drug: Placebo

BI 474121 5mg (Part B)

EXPERIMENTAL

Elderly participants administered 2 tablets of 2.5 mg BI 474121 orally once daily (daily dose: 5 mg) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.

Drug: BI 474121

BI 474121 10mg (Part B)

EXPERIMENTAL

Elderly participants administered 1 tablet of 10 milligrams (mg) BI 474121 orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.

Drug: BI 474121

Interventions

BI 474121 DRUG

BI474121

BI 474121 10mg (Part A); BI 474121 10mg (Part B); BI 474121 2.5mg (Part A); BI 474121 20mg (Part A); BI 474121 30mg (Part A); BI 474121 5mg (Part A); BI 474121 5mg (Part B); Placebo (Part A)

Midazolam DRUG

Midazolam

BI 474121 10mg (Part A); BI 474121 2.5mg (Part A); BI 474121 20mg (Part A); BI 474121 30mg (Part A); Placebo (Part A)

Placebo DRUG

Placebo

Placebo (Part A); Placebo (Part B)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
• Age of 18 to 45 years (inclusive) for young or 65 to 80 years (inclusive) for elderly healthy volunteers
• BMI of 18.5 to 29.9 kg/m2 (inclusive)
• Signed and dated written informed consent prior to admission to the study, in accordance with GCP and local legislation

You may not qualify if:

• Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
• Repeated measurement of systolic blood pressure outside the range of 100 to 140 mm Hg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Any evidence of a concomitant disease assessed as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
• Diseases of the central nervous system (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
• A positive Poly-chain reaction (PCR) test for SARS-CoV-2 and clinical symptoms suggestive for this disease at screening or on Day -3

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

CRS Clinical Research Services Mannheim GmbH

Mannheim, 68167, Germany

Location

Related Links

• Related Info

MeSH Terms

Interventions

Midazolam

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: August 31, 2020
• First Posted: September 3, 2020
• Study Start: October 6, 2020
• Primary Completion: October 7, 2021
• Study Completion: October 7, 2021
• Last Updated: March 8, 2024
• Results First Posted: March 8, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)