Influence of Fluvoxamine on the Pharmacokinetics of BI 409306

Influence of Fluvoxamine on the Pharmacokinetics of BI 409306 After Oral Administration (Randomized, Open-label, Two-treatment, Two-sequence, Two-period Crossover Study)

To investigate the influence of fluvoxamine on the pharmacokinetics of BI 409306

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BI 409306; Drug: BI 409306; Drug: Fluvoxamine

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

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany
    • 1289.35.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Healthy male or female 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.)
• 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

• Male or female subjects who meet any of the following criteria starting from screening until 30 days after trial completion regarding adequate contraception:

  • Non-hormonal intra-uterine device in combination with condom
  • Sexually abstinent
  • Surgically sterilised (including hysterectomy)
  • A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
  • Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of FSH above 40 U/L and estradiol below 30 ng/L is confirmatory)

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 100 to 140 mmHg, diastolic blood pressure outside the range of 60 to 90 mmHg, or pulse rate outside the range of 50 to 85 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 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
• Current smoker or ex-smoker who quit smoking less than 30 days prior to screening
• Alcohol abuse (consumption of more than 20 g per day for females and 30 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 repeatedly greater than 470 ms in females) 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
• History of major bleeding events (e.g. gastric bleeding, intracranial haemorrhage) based on the investigator's judgement
• Intake of drugs that may interfere with fluvoxamine such as monoamine oxidase inhibitors, and tizanidine.
• Intake of hormonal contraception or ovary hormone replacement therapy in female subjects
• Subjects with a medical history of suicidal behaviour
• History of increased intraocular pressure
• Positive pregnancy test, pregnancy or plans to become pregnant within 30 days after study completion
• Lactation period

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reference Treatment (pilot phase); BI 409306 low dose	Drug: BI 409306; low single dose; Drug: BI 409306; medium or high dose
Experimental: Test Treatment (pilot phase); Fluvoxamin and low dose of BI 409306	Drug: BI 409306; low single dose; Drug: BI 409306; medium or high dose; Drug: Fluvoxamine; single dose
Experimental: Reference Treatment (main phase); BI 409306 medium or high dose	Drug: BI 409306; low single dose; Drug: BI 409306; medium or high dose
Experimental: Test Treatment (main phase); Fluvoxamin and medium or high dose of BI 40930	Drug: BI 409306; low single dose; Drug: BI 409306; medium or high dose; Drug: Fluvoxamine; single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point	up to 72 hours
Maximum measured concentration of the analyte in plasma	up to 72 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity	up to 72 hours

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2016
• Primary Completion (Actual): October 17, 2016
• Study Completion (Actual): October 25, 2016

Study Registration Dates

• First Submitted: July 29, 2016
• First Submitted That Met QC Criteria: July 29, 2016
• First Posted (Estimate): August 2, 2016

Study Record Updates

• Last Update Posted (Actual): June 15, 2017
• Last Update Submitted That Met QC Criteria: June 14, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Anti-Anxiety Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Phosphodiesterase Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluvoxamine; BI 409306
• Other Study ID Numbers: 1289.35; 2016-000752-10 (EudraCT Number: EudraCT)