Phase 1
Completed N=24
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
Healthy
Source: ClinicalTrials.gov NCT04672954 ↗
Enrolled (actual)
24
Serious AEs
0.0%
Results posted
Mar 2024
Primary outcomePrimary: Maximum Exposure-related Change From Baseline (Calculated as Ratio) of Cyclic Guanosine Monophosphate (cGMP) in Cerebrospinal Fluid (CSF) — NA; NA; NA; NA maximum change from baseline cGMP ratio — p=0.3941
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
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Exposure-related Change From Baseline (Calculated as Ratio) of Cyclic Guanosine Monophosphate (cGMP) in Cerebrospinal Fluid (CSF) |
NA; NA; NA; NA; NA | 0.3941 |
| PRIMARY Maximum Measured Concentration (Cmax) Ratio of BI 474121 in Cerebrospinal Fluid (CSF) Compared to Plasma |
9.49; 7.88; 9.89; 8.42; 8.96 | — |
| SECONDARY Maximum Measured Concentration (Cmax) of BI 474121 in Plasma |
22.0; 87.2; 137; 278 | — |
| SECONDARY Maximum Measured Concentration (Cmax) of BI 474121 in Cerebrospinal Fluid (CSF) |
2.09; 6.87; 13.6; 23.5 | — |
| SECONDARY Time From Dosing to Maximum Measured BI 474121 Concentrations in Plasma (Tmax) |
4.00; 1.50; 2.01; 4.00 | — |
| SECONDARY Time From Dosing to Maximum Measured BI 474121 Concentrations in CSF (Tmax) |
2.03; 2.03; 3.02; 4.03 | — |
| SECONDARY Maximum Measured Exposure-related cGMP Concentration in Cerebrospinal Fluid (CSF) |
7.51; 9.54; 10.7; 7.36; 11.1 | — |
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
- Further exclusion criteria apply
Data sourced from ClinicalTrials.gov (NCT04672954). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.