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

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04537897

2020-001003-17 (EudraCT Number)

1411-0002

Details and patient eligibility

About

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.

Enrollment: 70 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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70 participants in 9 patient groups, including a placebo group

BI 474121 2.5mg (Part A)

Experimental group

Description:

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.

Treatment:

Drug: BI 474121

Drug: Midazolam

BI 474121 5mg (Part A)

Experimental group

Description:

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.

Treatment:

Drug: BI 474121

BI 474121 10mg (Part A)

Experimental group

Description:

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).

Treatment:

Drug: BI 474121

Drug: Midazolam

BI 474121 20mg (Part A)

Experimental group

Description:

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).

Treatment:

Drug: BI 474121

Drug: Midazolam

BI 474121 30mg (Part A)

Experimental group

Description:

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).

Treatment:

Drug: BI 474121

Drug: Midazolam

Placebo (Part A)

Placebo Comparator group

Description:

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.

Treatment:

Drug: BI 474121

Drug: Midazolam

Drug: Placebo

Placebo (Part B)

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

BI 474121 5mg (Part B)

Experimental group

Description:

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.

Treatment:

Drug: BI 474121

BI 474121 10mg (Part B)

Experimental group

Description:

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.

Treatment:

Drug: BI 474121