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

Healthy Clinical Trial

Official title:

Safety, Tolerability and Pharmacokinetics of Multiple Rising Oral Doses of BI 474121 in Young and Elderly Healthy Male and Female Subjects (Double-blind, Randomised, Placebo-controlled, Parallel Group Design) and Evaluation of Midazolam Interaction in Young Healthy Male and Female Subjects (Nested, Open, Fixed-sequence, Intra-individual Comparison)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04537897
• Other study ID #: 1411-0002
• Secondary ID: 2020-001003-17
• Status: Completed
• Phase: Phase 1
• Start date: October 6, 2020
• Est. completion date: October 7, 2021

Study information

• Verified date: July 2023
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: October 7, 2021
• Est. primary completion date: October 7, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Further exclusion criteria apply

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• BI 474121
BI474121
• Midazolam
Midazolam
• Placebo
Placebo

Locations

Country	Name	City	State
Germany	CRS Clinical Research Services Mannheim GmbH	Mannheim

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Area Under the Concentration-time Curve of BI 474121 in Plasma From 0 to 24h (AUC0-24) After First Dose	The area under the concentration-time curve of BI 474121 in plasma from 0 to 24h (AUC0-24) after first dose is reported.	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.
Secondary	Maximum Measured Concentration of BI 474121 in Plasma (Cmax) After First Dose	The maximum measured concentration of BI 474121 in plasma (Cmax) after first dose is reported.	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.
Secondary	Area Under the Concentration-time Curve of BI 474121 in Plasma at Steady State Over a Uniform Dosing Interval t (AUCt,ss)	The area under the concentration-time curve of BI 474121 in plasma at steady state over a uniform dosing interval t (dosing interval = 24 hours) (AUCt,ss) is reported.	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.
Secondary	Maximum Measured Concentration of BI 474121 in Plasma at Steady State Over a Uniform Dosing Interval t (Cmax,ss)	The maximum measured concentration of BI 474121 in plasma at steady state over a uniform dosing interval t (dosing interval = 24 hours) (Cmax,ss) is reported.	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.
Secondary	Maximum Measured Concentration of Midazolam in Plasma (Cmax) - Day -1	The maximum measured concentration of Midazolam in plasma (Cmax) on Day -1 is reported.	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.
Secondary	Maximum Measured Concentration of Midazolam in Plasma (Cmax) - Day 1	The Maximum measured concentration of Midazolam in plasma (Cmax) on Day 1 is reported.	Within 1 hour (h) before and at 15 minutes (min), 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 23h45min after administration of Midazolam on Day 1.
Secondary	Maximum Measured Concentration of Midazolam in Plasma (Cmax) - Day 14	The Maximum measured concentration of Midazolam in plasma (Cmax) on Day 14 is reported.	Within 15 minutes (min) before and at 15min, 30min, 1hour (h), 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h after administration of Midazolam on Day 14.
Secondary	Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) - Day -1	The area under the concentration-time curve of Midazolam in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) on Day -1 is reported.	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.
Secondary	Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) - Day 1	The Area under the concentration-time curve of Midazolam in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) on Day 1 is reported.	Within 1 hour (h) before and at 15 minutes (min), 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 23h45min after administration of Midazolam on Day 1.
Secondary	Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) - Day 14	The Area under the concentration-time curve of Midazolam in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) on Day 14 is reported.	Within 15 minutes (min) before and at 15min, 30min, 1hour (h), 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h after administration of Midazolam on Day 14.

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