HealthyPhase 1NCT04672954

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

A Phase 1 study testing 2.5 milligram (mg) BI 474121, 10 milligram (mg) BI 474121 and 20 milligram (mg) BI 474121 in people with Healthy, run by Boehringer Ingelheim at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 Read more about this study

Who is it for?: Ages 18 to 65 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: 2.5 milligram (mg) BI 474121, 10 milligram (mg) BI 474121 and 20 milligram (mg) BI 474121
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 24 participants
Where: 1 siteNetherlands
Study dates: 7 Jan 2021to 1 Jul 2021
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
Men only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

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)

Show all 9Show fewer

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

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

Centre Human Drug Research
Leiden, 2333 CL

Other trials in Netherlands

About this study

Official title: Pharmacokinetics and Pharmacodynamic Effects of Different Single Oral Doses of BI 474121 in Healthy Male Subjects

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
Being tested: Placebo, 2.5 milligram (mg) BI 474121, 10 milligram (mg) BI 474121, 20 milligram (mg) BI 474121, 40 milligram (mg) BI 474121

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
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 474121Drug
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 474121Drug
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 474121Drug
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 474121Drug
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.

Study groups in NCT04672954
Study group	Role	What they receive
Placebo	Placebo comparator	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. Receives: Drug: Placebo
2.5 milligram (mg) BI 474121	Experimental	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. Receives: Drug: 2.5 milligram (mg) BI 474121
10 milligram (mg) BI 474121	Experimental	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. Receives: Drug: 10 milligram (mg) BI 474121
20 milligram (mg) BI 474121	Experimental	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. Receives: Drug: 20 milligram (mg) BI 474121
40 milligram (mg) BI 474121	Experimental	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. Receives: Drug: 40 milligram (mg) BI 474121

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Exposure-related Change From Baseline (Calculated as Ratio) of Cyclic Guanosine Monophosphate (cGMP) in Cerebrospinal Fluid (CSF)
Maximum exposure-related change from baseline (calculated as ratio) of cyclic guanosine monophosphate (cGMP) in Cerebrospinal fluid (CSF). In subjects treated with BI 474121 this is the maximum cGMP value measured within 1 hour (h) prior and 4 h post BI 474121 Maximum measured concentration (Cmax) in CSF. For subjects treated with placebo, this is the maximum cGMP value measured within 1 h prior to and 4 h after the median BI 474121 tmax (time from (last) dosing to the maximum measured concentration of the analyte) in CSF of the BI 474121 treated subjects. Baseline cGMP concentration was calculated as the arithmetic mean of all pre-dose measurements above Lower limit of quantification (LLOQ) obtained in that subject. The maximum exposure-related change from baseline in cGMP in CSF was explored using an analysis of covariance (ANCOVA) model on the logarithmic scale. Maximum exposure related cGMP: Ratio [maximum cGMP / baseline cGMP].
Measured: 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.
Maximum Measured Concentration (Cmax) Ratio of BI 474121 in Cerebrospinal Fluid (CSF) Compared to Plasma
Maximum measured concentration (Cmax) ratio of BI 474121 in CSF compared to plasma. Mixed effects model: random effect 'subject nested within treatment', fixed effect, treatment, substance and their interaction' (for estimation of overall group effect the model was run without interaction term). Cmax was log transformed (natural logarithm) prior to fitting the model. Difference between expected means for log(CSF)- log(plasma) was estimated by difference in the corresponding least square means (point estimate) and two-sided 90% CI based on the t-distribution were computed. Quantities were back-transformed to the original scale to give an point estimator and interval estimate. Ratio = CSF (T) / plasma (R).
Plasma: Within 3 hours (h) before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 24, 34, 48 and 72 h following drug administration.
CSF: Within approximately 2, 1, and 0.17 h before and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 and 24 h following drug administration.
Measured: Up to 72 hours, see endpoint description for detailed sampling scheme.

Secondary outcomes (5)

Maximum Measured Concentration (Cmax) of BI 474121 in Plasma
Maximum measured concentration (Cmax) of BI 474121 in plasma.
Measured: 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.
Maximum Measured Concentration (Cmax) of BI 474121 in Cerebrospinal Fluid (CSF)
Maximum measured concentration (Cmax) of BI 474121 in Cerebrospinal fluid (CSF).
Measured: 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.
Time From Dosing to Maximum Measured BI 474121 Concentrations in Plasma (Tmax)
Time from dosing to maximum measured BI 474121 concentrations in plasma (tmax).
Measured: 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.
Time From Dosing to Maximum Measured BI 474121 Concentrations in CSF (Tmax)
Time from dosing to maximum measured BI 474121 concentrations in CSF (tmax).
Measured: 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.
Maximum Measured Exposure-related cGMP Concentration in Cerebrospinal Fluid (CSF)
Maximum measured exposure-related cGMP concentration in CSF. In subjects treated with BI 474121 this is the maximum cGMP value measured within 1 hour (h) prior and 4 h post BI 474121 Maximum measured concentration (Cmax) in CSF. For subjects treated with placebo, this is the maximum cGMP value measured within 1 h prior to and 4 h after the median BI 474121 tmax (time from (last) dosing to the maximum measured concentration of the analyte) in CSF of the BI 474121 treated subjects.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Jan 20211 Jul 2021

First posted17 Dec 2020
Study start7 Jan 2021
Primary completion1 Jul 2021
Study completion1 Jul 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
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.
Masking: Single blind
Who is masked: Participant
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04672954
Sponsor's protocol ID: 1411-0013
Other IDs: 2020-002321-28
Status last verified: Jul 2023
First submitted: 14 Dec 2020
Last updated: 8 Mar 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1\. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing

Publications

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.
PubMed 38880932

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacokinetics and Pharmacodynamic Effects of Different Single Oral Doses of BI 474121 in Healthy Male Subjects
ClinicalTrials.gov ID: NCT04672954
Acronym / sponsor ID: 1411-0013
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 7 Jan 2021 (actual)
Primary completion: 1 Jul 2021 (actual)
Study completion: 1 Jul 2021 (actual)
First posted: 17 Dec 2020 (actual)
Results: Posted 8 Mar 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 5
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.

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboPlacebo 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	Experimental	Drug: 2.5 milligram (mg) BI 4741212.5 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	Experimental	Drug: 10 milligram (mg) BI 47412110 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	Experimental	Drug: 20 milligram (mg) BI 47412120 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	Experimental	Drug: 40 milligram (mg) BI 47412140 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.

Who may qualify

Ages: 18 to 65 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboPlacebo 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.	Drug	Placebo
2.5 milligram (mg) BI 4741212.5 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.	Drug	2.5 milligram (mg) BI 474121
10 milligram (mg) BI 47412110 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.	Drug	10 milligram (mg) BI 474121
20 milligram (mg) BI 47412120 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.	Drug	20 milligram (mg) BI 474121
40 milligram (mg) BI 47412140 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.	Drug	40 milligram (mg) BI 474121

Primary outcome

Maximum Exposure-related Change From Baseline (Calculated as Ratio) of Cyclic Guanosine Monophosphate (cGMP) in Cerebrospinal Fluid (CSF)
Time frame: 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.
Maximum exposure-related change from baseline (calculated as ratio) of cyclic guanosine monophosphate (cGMP) in Cerebrospinal fluid (CSF). In subjects treated with BI 474121 this is the maximum cGMP value measured within 1 hour (h) prior and 4 h post BI 474121 Maximum measured concentration (Cmax) in CSF. For subjects treated with placebo, this is the maximum cGMP value measured within 1 h prior to and 4 h after the median BI 474121 tmax (time from (last) dosing to the maximum measured concentration of the analyte) in CSF of the BI 474121 treated subjects. Baseline cGMP concentration was calculated as the arithmetic mean of all pre-dose measurements above Lower limit of quantification (LLOQ) obtained in that subject. The maximum exposure-related change from baseline in cGMP in CSF was explored using an analysis of covariance (ANCOVA) model on the logarithmic scale. Maximum exposure related cGMP: Ratio [maximum cGMP / baseline cGMP].
Maximum Measured Concentration (Cmax) Ratio of BI 474121 in Cerebrospinal Fluid (CSF) Compared to Plasma
Time frame: Up to 72 hours, see endpoint description for detailed sampling scheme.
Maximum measured concentration (Cmax) ratio of BI 474121 in CSF compared to plasma. Mixed effects model: random effect 'subject nested within treatment', fixed effect, treatment, substance and their interaction' (for estimation of overall group effect the model was run without interaction term). Cmax was log transformed (natural logarithm) prior to fitting the model. Difference between expected means for log(CSF)- log(plasma) was estimated by difference in the corresponding least square means (point estimate) and two-sided 90% CI based on the t-distribution were computed. Quantities were back-transformed to the original scale to give an point estimator and interval estimate. Ratio = CSF (T) / plasma (R). Plasma: Within 3 hours (h) before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 24, 34, 48 and 72 h following drug administration. CSF: Within approximately 2, 1, and 0.17 h before and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 and 24 h following drug administration.

5 secondary outcomes

Maximum Measured Concentration (Cmax) of BI 474121 in Plasma
Time frame: 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.
Maximum Measured Concentration (Cmax) of BI 474121 in Cerebrospinal Fluid (CSF)
Time frame: 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.
Time From Dosing to Maximum Measured BI 474121 Concentrations in Plasma (Tmax)
Time frame: 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.
Time From Dosing to Maximum Measured BI 474121 Concentrations in CSF (Tmax)
Time frame: 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.
Maximum Measured Exposure-related cGMP Concentration in Cerebrospinal Fluid (CSF)
Time frame: 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.

Results and safety

Results posted to the registry on 8 Mar 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	4	4
2.5 Milligram (mg) BI 474121	4	4
10 Milligram (mg) BI 474121	4	4
20 Milligram (mg) BI 474121	6	6
40 Milligram (mg) BI 474121	6	6

Primary outcome: Maximum Exposure-related Change From Baseline (Calculated as Ratio) of Cyclic Guanosine Monophosphate (cGMP) in Cerebrospinal Fluid (CSF)

Time frame: 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.. Geometric mean (Standard Error). Unit: maximum change from baseline cGMP ratio

Measure	Placebo n = 4	2.5 Milligram (mg) BI 474121 n = 4	10 Milligram (mg) BI 474121 n = 4	20 Milligram (mg) BI 474121 n = 6	40 Milligram (mg) BI 474121 n = 5
Value	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)

Placebo vs 2.5 Milligram (mg) BI 474121: Ratio: 1.29 (90% CI 0.78 to 2.13), p = 0.3941, ANCOVA
Placebo vs 10 Milligram (mg) BI 474121: Ratio: 1.66 (90% CI 0.99 to 2.79), p = 0.1089, ANCOVA
Placebo vs 20 Milligram (mg) BI 474121: Ratio: 1.14 (90% CI 0.71 to 1.85), p = 0.6308, ANCOVA

Population analysed: Pharmacodynamic parameter analysis set (PDS): all evaluable subjects who were entered and treated with one dose of study drug and who provided at least one evaluable pre- and post-dose measure for a pharmacodynamic endpoint.

Primary outcome: Maximum Measured Concentration (Cmax) Ratio of BI 474121 in Cerebrospinal Fluid (CSF) Compared to Plasma

Time frame: Up to 72 hours, see endpoint description for detailed sampling scheme.. Geometric mean (90% Confidence Interval). Unit: Ratio [%] Cmax CSF (T) / Cmax Plasma (R)

Measure	2.5 Milligram (mg) BI 474121 n = 4	10 Milligram (mg) BI 474121 n = 4	20 Milligram (mg) BI 474121 n = 6	40 Milligram (mg) BI 474121 n = 5	Overall BI 474121 n = 19
Value	9.49 (8.27 to 10.89)	7.88 (6.86 to 9.04)	9.89 (8.84 to 11.07)	8.42 (7.45 to 9.53)	8.96 (8.37 to 9.59)

Population analysed: Pharmacokinetic parameter analysis set (PKS): This set includes all subjects who were entered and treated with one dose of study drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events: day of drug administration + 7 days, up to 7 days. All-cause mortality: day of drug administration till trial completion date, up to 14 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 4 (0%)	4 of 4 (100%)	0 of 4
2.5 Milligram (mg) BI 474121	0 of 4 (0%)	4 of 4 (100%)	0 of 4
10 Milligram (mg) BI 474121	0 of 4 (0%)	4 of 4 (100%)	0 of 4
20 Milligram (mg) BI 474121	0 of 6 (0%)	6 of 6 (100%)	0 of 6
40 Milligram (mg) BI 474121	0 of 6 (0%)	6 of 6 (100%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38880932van 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.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 2.5 milligram (mg) BI 474121, 10 milligram (mg) BI 474121 and 20 milligram (mg) BI 474121 in people with Healthy, run by Boehringer Ingelheim at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Exposure-related Change From Baseline (Calculated as Ratio) of Cyclic Guanosine Monophosphate (cGMP) in Cerebrospinal Fluid (CSF) (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04672954, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2024.