Relative Bioavailability of a Single Oral Dose of BI 425809 When Administered Alone or in Combination With Multiple Oral Doses of Itraconazole in Healthy Male Subjects

Relative Bioavailability of a Single Oral Dose of BI 425809 When Administered Alone or in Combination With Multiple Oral Doses of Itraconazole in Healthy Male Subjects (an Open-label, Two-period, Fixed-sequence Trial)

To investigate whether and to what extent co-administration of multiple doses of itraconazole affect single dose pharmacokinetics of BI 425809 in healthy male subjects

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BI 425809; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany
    • 1346.10.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

• Healthy male subjects according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
• Age of 18 to 50 years (incl.)
• Body mass index (BMI) of 18.5 to 29.9 kg/m2 (incl.)
• Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation

Exclusion criteria:

• Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator
• Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 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 judged as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and 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
• Chronic or relevant acute infections
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
• Intake of drugs with a long half-life (more than 24 h) within 30 days or less than 10 halflives of the respective drug prior to administration of trial medication
• Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval
• Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication
• Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
• Inability to refrain from smoking on specified trial days
• Alcohol abuse (consumption of more than 30 g per day)
• Drug abuse or positive drug screening
• Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
• Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
• Inability to comply with dietary regimen of trial site
• A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening
• A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
• Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
• Male subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until two month after the trial completion. Acceptable methods of contraception comprise barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive for at least two month prior trial participation)
• Known fructose intolerance, glucose-galactose malabsorption, or saccharose-isomaltase deficiency
• History of relevant liver diseases such as disturbance of liver function, jaundice, drug induced liver injury, Dubin-Johnson syndrome, Rotor syndrome, or liver tumours
• Liver enzymes (ALT, AST, GGT) above upper limit of normal at the screening examination

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reference; single dose BI 425809	Drug: BI 425809; single dose BI 425809 tablet; Other Names: Iclepertin
Experimental: Test; multiple doses of Itraconazole + single dose BI 425809	Drug: BI 425809; single dose BI 425809 tablet; Other Names: Iclepertin; Drug: Itraconazole; multiple doses of Itraconazole capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-167 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 167 h)	8 days postdose
Cmax (maximum measured concentration of the analyte in plasma)	15 days postdose

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)	15 days postdose

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

General Publications

• Desch M, Wunderlich G, Goettel M, Goetz S, Liesenfeld KH, Chan TS, Rosenbrock H, Sennewald R, Link J, Keller S, Wind S. Effects of Cytochrome P450 3A4 Induction and Inhibition on the Pharmacokinetics of BI 425809, a Novel Glycine Transporter 1 Inhibitor. Eur J Drug Metab Pharmacokinet. 2022 Jan;47(1):91-103. doi: 10.1007/s13318-021-00723-y. Epub 2021 Oct 29.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: January 15, 2015
• First Submitted That Met QC Criteria: January 15, 2015
• First Posted (Estimated): January 21, 2015

Study Record Updates

• Last Update Posted (Actual): September 20, 2024
• Last Update Submitted That Met QC Criteria: September 19, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Nootropic Agents; 14-alpha Demethylase Inhibitors; Itraconazole; BI 425809
• Other Study ID Numbers: 1346.10; 2014-004855-29 (EudraCT Number: EudraCT)