A Study in Healthy Men to Test How Itraconazole Influences the Amount of BI 894416 in the Blood

• ClinicalTrials.gov Identifier: NCT03722173
• Recruitment Status: Completed
• First Posted: October 26, 2018
• Last Update Posted: January 10, 2019
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief Summary:

The main objective of this trial is to investigate the relative bioavailability of BI 894416 in plasma when given as oral single dose together with multiple oral doses of itraconazole (Test,T) as compared to when given alone as oral single dose (Reference, R).

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Itraconazole; Drug: BI 894416	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Relative Bioavailability of a Single Oral Dose of BI 894416 When Administered Alone or in Combination With Multiple Oral Doses of Itraconazole in Healthy Male Subjects (an Open-label, One-way Crossover Study)
• Actual Study Start Date: November 13, 2018
• Actual Primary Completion Date: December 14, 2018
• Actual Study Completion Date: December 18, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: All subjects; Period 1:Treatment R (BI 894416 alone) followed by Period 2:Treatment T (BI 894416 + itraconazole)	Drug: Itraconazole; Oral solution; Drug: BI 894416; Tablet

Outcome Measures

Primary Outcome Measures :

1. AUC0-tz (area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 to the last quantifiable data point) [ Time Frame: Up to 72 hours ]
2. Cmax (maximum measured concentration of BI 894416 in plasma) [ Time Frame: Up to 72 hours ]

Secondary Outcome Measures :

1. AUC0-∞ (area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity) [ Time Frame: Up to 72 hours ]

Eligibility Criteria

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

Criteria

Inclusion criteria:

• 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 50 years (inclusive)
• Body Mass Index (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

Exclusion criteria:

• Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG) and including the neurological examination) deviating from normal and assessed 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 45 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 assessed as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or 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 of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/QTc interval prolongation)
• Intake of an investigational drug in another clinical trial within 60 days of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered
• Smoker (unless the subject quit smoking for at least 1 year prior to first planned administration of trial medication)
• 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 of planned administration of trial medication or intended blood donation during the trial
• Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial
• Inability to comply with the dietary regimen of the 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 Torsade 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 the subject is not considered able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
• History of relevant neurological disorder affecting the peripheral or central nervous system (this includes, but is not limited to: stroke, epilepsy, inflammatory or atrophic diseases affecting the nervous system, cluster headache or any cancer of the nervous system). Febrile seizures in childhood or adolescence, recovered carpal tunnel syndrome, recovered uncomplicated meningitis, recovered herpes zoster, tension headache, occasional benign tics (e.g. due to stress) or minor par- or dysesthesia (e.g. as a side effect of prior blood withdrawal) do not constitute a history of relevant neurological disorder.
• History of immunological disease except allergy not relevant to the trial (such as mild hay fever or dust mite allergy) and except asthma in childhood or adolescence
• History of cancer (other than successfully treated basal cell carcinoma)
• 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)
• Liver enzyme (ALT, AST, gGT) values above upper limit of normal at the screening examination
• History of drug-induced liver injury
• History of heart failure, or any evidence of ventricular dysfunction in the history
• History of hereditary fructose intolerance
• Male subjects with woman of child bearing potential (WOCBP) partner who are unwilling to use male contraception (condom or sexual abstinence) from time point of first administration of trial medication until 30 days after the last administration of trial medication

Contacts and Locations

Locations

Germany

Humanpharmakologisches Zentrum Biberach

Biberach, Germany, 88397

Sponsors and Collaborators

Boehringer Ingelheim

More Information

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT03722173
• Other Study ID Numbers: 1371-0004; 2018-002728-17 ( EudraCT Number )
• First Posted: October 26, 2018
• Last Update Posted: January 10, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Plan Description

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). Requestors can use the following link http:// trials.boehringer-ingelheim.com/ to:

1. find information in order to request access to clinical study data, for listed studies.
2. request access to clinical study documents that meet criteria, and upon a signed 'Document Sharing Agreement'.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Itraconazole; Antifungal Agents; Anti-Infective Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP3A Inhibitors