A Study in Healthy Men to Test How Different Doses of BI 474121 Are Taken up and How They Influence the Amount of a Molecular Messenger (cGMP) in the Spinal Fluid

NCT ID: NCT04672954

Last Updated: 2024-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-07
• Study Completion Date: 2021-07-01

Brief Summary

The main objectives of this trial are:

• To evaluate the effect of BI 474121 on cyclic guanosine monophosphate (cGMP) levels in cerebrospinal fluid (CSF)
• To assess the exposure of BI 474121 in CSF relative to plasma
• To determine the exposure effect relationship in CSF with different oral doses of BI 474121

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Placebo

Placebo matching to 10 mg BI 474121 administered as uncoated tablets with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 1: randomised, placebo-controlled, single-blind.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matching to 10 mg BI 474121 administered as uncoated tablets with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 1: randomised, placebo-controlled, single-blind.

2.5 milligram (mg) BI 474121

2.5 mg BI 474121 administered as uncoated tablets (1 x 2.5 mg) with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 3 of the study: randomised, open-label.

Group Type: EXPERIMENTAL

2.5 milligram (mg) BI 474121

Intervention Type: DRUG

2.5 mg BI 474121 administered as uncoated tablets (1 x 2.5 mg) with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 3 of the study: randomised, open-label.

10 milligram (mg) BI 474121

10 mg BI 474121 administered as uncoated tablets (1 x 10 mg) with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 3 of the study: randomised, open-label.

Group Type: EXPERIMENTAL

10 milligram (mg) BI 474121

Intervention Type: DRUG

10 mg BI 474121 administered as uncoated tablets (1 x 10 mg) with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 3 of the study: randomised, open-label.

20 milligram (mg) BI 474121

20 mg BI 474121 administered as uncoated tablets (2 x 10 mg) with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 1 of the study: randomised, placebo-controlled, single-blind.

Group Type: EXPERIMENTAL

20 milligram (mg) BI 474121

Intervention Type: DRUG

20 mg BI 474121 administered as uncoated tablets (2 x 10 mg) with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 1 of the study: randomised, placebo-controlled, single-blind.

40 milligram (mg) BI 474121

40 mg BI 474121 administered as uncoated tablets (4 x 10 mg) with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 2 of the study: non-randomised, open-label.

Group Type: EXPERIMENTAL

40 milligram (mg) BI 474121

Intervention Type: DRUG

40 mg BI 474121 administered as uncoated tablets (4 x 10 mg) with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 2 of the study: non-randomised, open-label.

Interventions

Placebo

Placebo matching to 10 mg BI 474121 administered as uncoated tablets with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 1: randomised, placebo-controlled, single-blind.

Intervention Type: DRUG

2.5 milligram (mg) BI 474121

2.5 mg BI 474121 administered as uncoated tablets (1 x 2.5 mg) with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 3 of the study: randomised, open-label.

Intervention Type: DRUG

10 milligram (mg) BI 474121

10 mg BI 474121 administered as uncoated tablets (1 x 10 mg) with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 3 of the study: randomised, open-label.

Intervention Type: DRUG

20 milligram (mg) BI 474121

20 mg BI 474121 administered as uncoated tablets (2 x 10 mg) with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 1 of the study: randomised, placebo-controlled, single-blind.

Intervention Type: DRUG

40 milligram (mg) BI 474121

40 mg BI 474121 administered as uncoated tablets (4 x 10 mg) with 240 milliliter of water after subjects fasted overnight for at least 10 hours. This arm was part of Part 2 of the study: non-randomised, open-label.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
• Age of 18 to 65 years (inclusive)
• 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 Good Clinical Practice (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 90 to 150 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 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 assessed as clinically relevant by the investigator
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Centre Human Drug Research

Leiden, , Netherlands

Countries

Netherlands

References

van Kraaij S, Goeldner RG, Rosenbrock H, Groeneveld GJ, Kremer P, Schaible J, Zambori J, Schultheis C. Effects of the phosphodiesterase 2 inhibitor BI 474121 on central nervous system cyclic guanosine monophosphate concentrations: Translational studies. Br J Clin Pharmacol. 2024 Oct;90(10):2517-2528. doi: 10.1111/bcp.16137. Epub 2024 Jun 16.

Reference Type: DERIVED

PMID: 38880932 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.mystudywindow.com

Related Info

Other Identifiers

2020-002321-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1411-0013

Identifier Type: -

Identifier Source: org_study_id