Open-label, randomised, 4 parallel-group, Phase I clinical trial to investigate BI 456906 occupancy of Glucagon receptors in liver and Glucagon-like Peptide 1 receptors in pancreas in comparison with semaglutide after administration of radiolabeled tracer in male and female subjects with obesity using PET and MRI

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 30

Inclusion Criteria

1. 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
2. Age of 18 to 65 years (inclusive)
3. BMI of >=30 and <=40 kg/m2 and body weight >=70 kg and <=150 kg.
4. Signed and dated written informed consent prior to admission to the study,
in accordance with GCP and local legislation
5. Women of childbearing potential (WOCBP) 1 must be willing and able to use
two forms of effective contraception where at least one form is a highly
effective method of birth control per ICH M3 (R2) that result in a low failure
rate of less than 1% per year when used consistently and correctly. A list of
contraception methods meeting these criteria is provided in the subject
information (Section 4.2.2.3).

Exclusion Criteria

Subjects will not be allowed to participate if any of the following general
criteria apply:
1. Any finding in the medical examination (including BP, PR or ECG) deviating
from normal and assessed as clinically relevant by the investigator
2. Resting heart rate >100 beats per minute (bpm) and/or systolic blood
pressure >=160 mmHg and/or diastolic blood pressure >=95 mmHg at screening
3. Any laboratory value outside the reference range that the investigator
considers to be of clinical relevance. Subjects with the following abnormal
values are not eligible for the trial participation:
- LDL >160 mg/dL (4.15 mmol/L)
- total cholesterol >240 mg/dL (6.22 mmol/L)
- triglyceride >200 mg/dL (2.26 mmol/L)
- blood glucose >126 mg/dl (7 mmol/L) fasting and/or HbA1c >6.5%
4. Any evidence of a concomitant disease assessed as clinically relevant by the
investigator. Subjects with type 1 and type 2 diabetes mellitus are not
eligible for the trial
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,
immunological or hormonal disorders assessed as clinically relevant by the
investigator
6. Diseases of the central nervous system (including but not limited to any
kind of seizures), and other relevant neurological or psychiatric disorders
7. History of relevant orthostatic hypotension, fainting spells, or blackouts
8. Personal or family history of medullary thyroid carcinoma or multiple
endocrine neoplasia syndrome type 2, manifest hypo- or hyperthyroidism at Visit
1
9. Calcitonin >=100 pg/mL (29.26 pmol/L) at screening
10. Any suicidal behaviour or history of major depressive disorder requiring
inpatient treatment or escalation of care in the past 2 years before
randomization, any suicidal ideation of type 4 or 5 in the C-SSRS in the past 3
months prior to Visit 1
11. Chronic or relevant acute infections
12. History of chronic or acute pancreatitis or elevation of serum
lipase/amylase >2x ULN
13. History of relevant allergy or hypersensitivity (including allergy to the
trial medication or its excipients) according to investigator's assessment
14. Use of prescription or over-the counter drugs within 30 days of planned
administration of trial medication that might reasonably influence the results
of the trial including drugs known to significantly prolong the QT/QTcF
interval; please refer to Section 4.2.2
15. Intake of an investigational drug in another clinical trial within 60 d of
planned administration of investigational drug in the current trial, or
concurrent participation in another clinical trial in which investigational
drug is administered
16. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day) and
inability to refrain from smoking on specified trial days
17. Ongoing chronic alcohol use or drug abuse other than the ones described in
Table 5.2.3: 2, that in the investigator*s opinion, makes the subject an
unreliable trial subject or unlikely to complete the trial
18. Blood donation of more than 500 mL within 30 d of planned administration of
trial medication or intended blood donation during the trial
19. Intention to perform excessive physical activities within one week prior to
the administration of trial medication or during the trial
20. Inability to comply with the dietary regimen of the trial site
21. A marked baseline p

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoint:<br /><br>· Percentage of glucagon receptors occupancy in the liver using PET imaging at<br /><br>End of Treatment visit (EOT).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secundary endpoints:<br /><br>· Percentage of glucagon-like Peptide 1 receptor occupancy in the pancreas<br /><br>using PET imaging at EOT visit.</p><br>