A study in healthy Japanese men to test how different doses of BI 1323495 are tolerated and how itraconazole influences the amount of BI 1323495 in the blood

JRCT ID: jRCT2071200056

Registered date:25/11/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Healthy Volunteer
• Date of first enrollment: 16/11/2020
• Target sample size: 74
• Study type: Interventional

Intervention(s)

SDR Part: Single dose of BI 1323495
DDI part: Single dose of BI 1323495, after that, single dose of BI 1323495 combined with itoraconazole treatment
MD Part: Multiple doses of BI 1323495

Outcome(s)

Primary Outcome

SRD part: to assess safety and tolerability of BI 1323495 is the percentage (%) of subjects with drug-related adverse events

DDI part: Cmax and AUC0- of BI 1323495

MD part: to assess safety and tolerability of BI 1323495 is the percentage (%) of subjects with drug-related adverse events

Secondary Outcome

SRD part: Cmax, and AUC0- of BI 1323495
DDI part: AUC0-tz of BI 1323495
MD part: After the first dose: AUC0-12 and Cmax of BI 1323495
After the last dose: AUCT,ss and Cmax,ss of BI 1323495

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 45age old
• Gender: Male

Include criteria

1. Healthy male subjects according to the assessment of the investigator, as based on a complete medical history, including a medical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
2. Japanese ethnicity, according to the following criteria:
- born in Japan, have lived outside of Japan <10 years, and have parents and grandparents who are Japanese
3. Age of 20 to 45 years (inclusive) at screening
4. BMI of 18.5 to 25.0 kg/m2 (inclusive) at screening
5. Signed and dated written informed consent prior to admission to the trial, in accordance with Good Clinical Practice (GCP) and local legislation
6. Subjects who agree to minimize the risk of making their partner pregnant by fulfilling any of the following criteria starting from the first administration of trial medication until 90 days after last administration of trial medication
- Use of adequate contraception, any of the following methods plus condom: intrauterine device, combined oral contraceptives that started at least 2 months prior to the first drug administration.
- Vasectomized (vasectomy at least 1 year prior to enrolment)
- Surgical sterilization (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subject's female partner
7. Subjects genotyped as UGT2B17 poor metabolizers, i.e. carrying allele of UGT2B17 gene (2/2) (DDI and MD part only)

Exclude criteria

1.Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
2.Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 40 to 90 mmHg, or pulse rate outside the range of 40 to 99 bpm
3.Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
4.Any evidence of a concomitant disease assessed as clinically relevant by the investigator
5.Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
6.Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
7.Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
8.History of relevant orthostatic hypotension, fainting spells, or blackouts
9.Chronic or relevant acute infections (Subjects who were positives to Hepatitis B surface antigen, Hepatitis B surface antibody, Hepatitis B core antibody, Hepatitis C antibodies, HIV-1 and HIV-2 antigen and/or antibody, T-SPOT and Syphilis test)
10.History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
11.Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/QTc interval prolongation)
12.Intake of an investigational drug in another clinical trial within 3 months (4 months for new active ingredients) of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered
13.Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
14.Inability to refrain from smoking on specified trial days
15.Alcohol abuse (consumption of more than 30 g per day for males)
16.Drug abuse or positive drug screening
17.Blood donation of more than 400 mL within 12 weeks or 200 mL within 30 days or plasma donation within 2 weeks prior to administration or intended blood donation during the trial
18.Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial
19.Inability to comply with the dietary regimen of the trial site
20.A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms in males) or any other relevant ECG finding at screening
21.A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome)
22.Subject is assessed as unsuitable for inclusion by the investigator, for instance, because the subject is not considered able to understand and comply with trial requirements, or has a condition that would not allow safe participation in the trial
23.History of disease that affects the present situation
24.Current or history of relevant kidney, urinary tract diseases or abnormalities (e.g. nephrolithiasis, hydronephrosis, acute or chronic nephritis, renal injury, renal failure)
25.Estimated glomerular filtration rate according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula < 80 mL/min at screening
26.Within 10 days prior to administration of trial medication, use of any drug that could reasonably inhibit platelet aggregation or coagulation (e.g. acetylsalicylic acid)
27.History of drug induced liver injury
28.Liver enzymes (ALT, AST, Gamma-Glutamyl Transferase [GGT]) above upper limit of normal at the screening examination
29. Known relevant immunodeficiency, as judged by the investigator
30.History and/or presence of tuberculosis; positive result for interferon gamma release assay (IGRA) (i.e. T-SPOT), or history of pneumococcal infection
31.Axillary temperature of more than 37.7oC on Day -1
32.Subjects who have received live or live-attenuated vaccine in the 4 weeks prior to dosing
33.C-reactive protein above upper limit of laboratory reference range at screening

Related Information

• Primary Sponsor: Katakabe Tetsuya