Clinical trial NCT04672954: 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
Official title: Pharmacokinetics and Pharmacodynamic Effects of Different Single Oral Doses of BI 474121 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2020-12-17
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial is designed to have three parts. Part 1: single-blind, randomized, placebo-controlled. Part 2: open-label, non-randomized. Part 3: open-label, randomized.
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Maximum Exposure-related Change From Baseline (Calculated as Ratio) of Cyclic Guanosine Monophosphate (cGMP) in Cerebrospinal Fluid (CSF)
timeFrame: Within approximately 2, 1, and 0.17 hours before and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 and 24 hours following drug administration.
measure: Maximum Measured Concentration (Cmax) Ratio of BI 474121 in Cerebrospinal Fluid (CSF) Compared to Plasma
timeFrame: Up to 72 hours, see endpoint description for detailed sampling scheme.
Secondary outcomes:
measure: Maximum Measured Concentration (Cmax) of BI 474121 in Plasma
timeFrame: Within 3 hours before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 24, 34, 48 and 72 hours following drug administration.
measure: Maximum Measured Concentration (Cmax) of BI 474121 in Cerebrospinal Fluid (CSF)
timeFrame: Within approximately 2, 1, and 0.17 hours before and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 and 24 hours following drug administration.
measure: Time From Dosing to Maximum Measured BI 474121 Concentrations in Plasma (Tmax)
timeFrame: Within 3 hours before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 24, 34, 48 and 72 hours following drug administration.
measure: Time From Dosing to Maximum Measured BI 474121 Concentrations in CSF (Tmax)
timeFrame: Within approximately 2, 1, and 0.17 hours before and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 and 24 hours following drug administration.
measure: Maximum Measured Exposure-related cGMP Concentration in Cerebrospinal Fluid (CSF)
timeFrame: Within approximately 2, 1, and 0.17 hours before and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 and 24 hours following drug administration.
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Centre Human Drug Research
Study officials:
References: