Relative Bioavailability of BI 1467335 Tablet and Oral Solution, and Food Effect on Tablet in Healthy Male Subjects

Relative Bioavailability of a BI 1467335 Tablet Compared to a BI 1467335 Oral Solution and the Effect of Food on the Bioavailability of the Tablet Following Oral Administration (a Randomised, Open-label, Single Dose, Three-way Crossover Trial in Healthy Male Subjects)

The primary objective of this trial is to investigate the relative bioavailability of BI 1467335, given as film-coated tablet compared to BI 1467335, given as oral solution. This assessment will be performed under fasted conditions. Furthermore, the effect of food on relative bioavailability of the tablet formulation of BI 1467335 will be investigated.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: BI 1467335 (Treatment A); Drug: BI 1467335 (Treatment B); Drug: BI 1467335 (Treatment C)

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany, 88397
    • Humanpharmakologisches Zentrum Biberach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects according to the investigators assessment, 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 55 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 Good Clinical Practice (GCP) and local legislation

• Willingness to comply with contraception requirements. Subjects who are sexually active, must use, with their female partner, adequate contraception throughout the study and until one month after the last administration of trial medication. Adequate methods are:

  • Sexual abstinence or
  • A vasectomy performed at least 1 year prior to screening in combination with a barrier method (condom or diaphragm) or
  • Surgical sterilisation (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subjects female partner or
  • The use of condoms, if the female partner uses in addition an adequate contraception method, e.g., intrauterine device (IUD), hormonal contraception (e.g. implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first drug administration, or barrier method (e.g. diaphragm with spermicide) Unprotected sexual intercourse with a pregnant female partner is not allowed throughout the study and until one month after the last administration of trial medication.

Exclusion Criteria:

• Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (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 beats per minute (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)
• Use of drugs within 30 days prior to administration of trial medication, if that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation)
• Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication or current participation in another trial involving administration of investigational drug
• 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 7 days 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, hypokalaemia, 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

In addition, the following trial-specific exclusion criteria apply:

- Cataract in the medical history

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 1467335 (Treatment A); Tablet under fasted conditions	Drug: BI 1467335 (Treatment A)
Experimental: BI 1467335 (Treatment B); Oral solution under fasted conditions	Drug: BI 1467335 (Treatment B)
Experimental: BI 1467335 (Treatment C); Tablet under fed conditions	Drug: BI 1467335 (Treatment C)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-tz of BI 1467335	This outcome measure presents AUC0-tz [area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to the last quantifiable data point].	At -1:00h [hours (h): minutes (min)] before drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 and 24:00 h:min after drug administration.
Cmax of BI 1467335	This outcome measure presents the maximum measured concentration of BI 1467335 in plasma (Cmax of BI 1467335).	At -1:00h [hours (h): minutes (min)] before drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 and 24:00 h:min after drug administration.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2017
• Primary Completion (Actual): March 15, 2017
• Study Completion (Actual): April 10, 2017

Study Registration Dates

• First Submitted: December 19, 2016
• First Submitted That Met QC Criteria: December 19, 2016
• First Posted (Estimate): December 21, 2016

Study Record Updates

• Last Update Posted (Actual): June 7, 2021
• Last Update Submitted That Met QC Criteria: May 11, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 1386.17; 2016-001534-97 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No