Drug-drug Interaction (DDI) With a P-gp Inhibitor, Organic Anion Transporting Polypeptide OATP-inhibitor, Food Effect

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03116893
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 4
• Actual Duration (Months): 1.4
• Patients Per Site Per Month: 10.9

Study Details

Study Description

Brief Summary

The primary objective of this trial is to investigate the relative bioavailability of BI 685509 given alone under fasted conditions (Reference, R) compared to the intake after a high fat, high caloric breakfast (Test 1, T1), to combined administration with itraconazole under fasted conditions (Test 2, T2) and to combined administration with rifampin under fasted conditions (Test 3, T3).

The secondary objective is the evaluation and comparison of several pharmacokinetic parameters between the treatments.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: BI 685509 After Standardised Breakfast; Drug: Itraconazole; Drug: Rifampin; Drug: BI 685509 Fasted Conditions	Phase 1

Detailed Description

BI 685509 is a substrate of the drug transporters P-gp and Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1/OATP1B3). Inhibition of these transport proteins may result in an increased drug exposure which might impact the safety of the patients. Therefore this trial should investigate whether and to what extent the inhibition of P-gp (mediated by itraconazole) and the inhibition of OATP1B1/OATP1B3 (mediated by rifampin) affects kinetics of BI 685509. Itraconazole and rifampin are recommended probe drugs to test in-vivo inhibition of P-gp and OATP1B1/OATP1B3.

Furthermore the food effect will be investigated in this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of P-gp Inhibition, OATP-inhibition and Food on the Kinetics of a Single Oral Dose BI 685509 in Healthy Male Subjects
• Actual Study Start Date: Apr 19, 2017
• Actual Primary Completion Date: May 31, 2017
• Actual Study Completion Date: May 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Reference Treatment BI 685509 given alone, fasted	Drug: BI 685509 Fasted Conditions; BI 685509, given alone
Experimental: Treatment 1 BI 685509, given alone, after a high fat, high calorie breakfast	Drug: BI 685509 After Standardised Breakfast; High-fat high calorie breakfast
Experimental: Treatment 2 BI 685509, given together with itraconazole, fasted	Drug: Itraconazole; Administration of itraconazole together with BI 685509
Experimental: Treatment 3 BI 685509, given together with rifampicin, fasted	Drug: Rifampin; Administration of rifampicin together with BI 685509

Outcome Measures

Primary Outcome Measures

1. AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) [4 Days]

   AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)

2. Cmax (maximum measured concentration of the analyte in plasma) [4 Days]

   Cmax (maximum measured concentration of the analyte in plasma)

Secondary Outcome Measures

1. AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) [4 Days]

   AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

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 100 to 140 mmHg, diastolic blood pressure outside the range of 60 to 90 mmHg, or pulse rate outside the range of 45 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)

• Use of drugs within 30 days prior to administration of trial medication if that might reasonably influence the results of the trial (incl. Time between start of the Q-wave and the end of the T-wave in an electrocardiogram/ corrected QT interval [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

• 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 24 g per day for males)

• 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 in males or any other relevant Electrocardiogram [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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Humanpharmakologisches Zentrum Biberach	Biberach		Germany	88397

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT03116893
• Other Study ID Numbers: 1366-0010; 2016-003310-27
• First Posted: Apr 17, 2017
• Last Update Posted: Jun 7, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Itraconazole; Rifampin

Study Results

No Results Posted as of Jun 7, 2017