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: Fluvoxamine; Drug: BI 409306 - Powder for oral solution (PfOS); Drug: BI 409306 - film coated tablet

• 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 50 years (Adult)
• Accepts Healthy Volunteers: Yes

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: 3 mg BI 409306 [R1]/3 mg BI 409306 + 100 mg Fluvoxamine [T1]; The subjects were administered 3 milligram [mg] BI 409306 Powder for Oral Solution [PfOS] single dose for one day in the pilot phase, taken as 6 mL of 0.5 mg/mL BI 409306 solved in 5 mg/mL [milliLiter] tartaric acid orally with 240 mL of water after an overnight fast of at least 10h, followed by 3 mg BI 409306 PfOS single dose for one day together with 100 mg Fluvoxamine [Fevarin®] film-coated tablet once daily orally with 240 mL of water after an overnight fast of at least 10h. Prior to the combined treatment, Fluvoxamine was given for 3 days: 50 mg twice daily on Day -3, followed by 100 mg bid on Day -2 and Day -1. There was a washout of at least 3 days after administration of BI 409306 in R1.	Drug: Fluvoxamine; Fluvoxamine; Other Names: Fevarin®; Drug: BI 409306 - Powder for oral solution (PfOS); BI 409306 - Powder for oral solution (PfOS)
Experimental: 3 mg BI 409306 + 100 mg Fluvoxamine [T1]/3 mg BI 409306 [R1]; The subjects were administered 3 mg BI 409306 PfOS single dose for one day in the pilot phase together with 100 mg Fluvoxamine [Fevarin®] film-coated tablet once daily orally with 240 mL of water after an overnight fast of at least 10h, followed by 3 mg BI 409306 PfOS single dose for one day orally with 240 mL of water after an overnight fast of at least 10h. Prior to the combined treatment, Fluvoxamine was given for 3 days: 50 mg twice daily on Day -3, followed by 100 mg bid on Day -2 and Day -1. There was a washout of at least 6 days after combined administration of BI 409306 and Fluvoxamine in T1.	Drug: Fluvoxamine; Fluvoxamine; Other Names: Fevarin®; Drug: BI 409306 - Powder for oral solution (PfOS); BI 409306 - Powder for oral solution (PfOS)
Experimental: 10 mg BI 409306 [R2]/10 mg BI 409306 + 100 mg Fluvoxamine [T2]; The subjects were administered 10 mg BI 409306 film-coated tablet single dose for one day in the main phase orally with 240 mL of water after an overnight fast of at least 10h, followed by 10 mg BI 409306 film-coated tablet single dose for one day together with 100 mg Fluvoxamine [Fevarin®] film-coated tablet once daily orally with 240 mL of water after an overnight fast of at least 10h. Prior to the combined treatment, Fluvoxamine was given for 3 days: 50 mg twice daily on Day -3, followed by 100 mg bid on Day -2 and Day -1. There was a washout of at least 3 days after administration of BI 409306 in R2.	Drug: Fluvoxamine; Fluvoxamine; Other Names: Fevarin®; Drug: BI 409306 - film coated tablet; BI 409306 - film coated tablet
Experimental: 10 mg BI 409306 + 100 mg Fluvoxamine [T2]/10 mg BI 409306 [R2]; The subjects were administered 10 mg BI 409306 film-coated tablet single dose for one day in the main phase together with 100 mg Fluvoxamine [Fevarin®] film-coated tablet once daily orally with 240 mL of water after an overnight fast of at least 10h, followed by 10 mg BI 409306 single dose film-coated tablet for one day orally with 240 mL of water after an overnight fast of at least 10h. Prior to the combined treatment, Fluvoxamine was given for 3 days: 50 mg twice daily on Day -3, followed by 100 mg bid on Day -2 and Day -1. There was a washout of at least 6 days after combined administration of BI 409306 and Fluvoxamine in T2.	Drug: Fluvoxamine; Fluvoxamine; Other Names: Fevarin®; Drug: BI 409306 - film coated tablet; BI 409306 - film coated tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	This outcome measured the area under the concentration-time curve of BI 409306 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) in the main phase of the trial (10mg BI 409306 + 100 mg Fluvoxamine (T2) and 10 mg BI 409306 (R2)), as defined in the clinical trial protocol. The statistical model used for the analysis of the endpoint was an ANOVA (Analysis of Variance) model. This model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.	-2:00h (hours: minutes) before drug administration and 0:20h, 0:30h, 0:45h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration.
Maximum Measured Concentration of BI 409306 in Plasma (Cmax)	This outcome measure presents the maximum measured concentration of BI 409306 in plasma in the main phase of the trial (10mg BI 409306 + 100 mg Fluvoxamine (T2) and 10 mg BI 409306 (R2)), as defined in the clinical trial protocol. The statistical model used for the analysis of the endpoint was an ANOVA (Analysis of Variance) model. This model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.	-2:00h (hours: minutes) before drug administration and 0:20h, 0:30h, 0:45h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity)	This outcome measure presents AUC0-infinity (area under the concentration-time curve of BI 409306 in plasma over the time interval from 0 extrapolated to infinity) in the main phase of the trial (10mg BI 409306 + 100 mg Fluvoxamine (T2) and 10 mg BI 409306 (R2)), as defined in the clinical trial protocol. The statistical model used for the analysis of the endpoint was an ANOVA (Analysis of Variance) model. This model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.	-2:00h (hours: minutes) before drug administration and 0:20h, 0:30h, 0:45h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration.

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Related Info

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 (Estimated): August 2, 2016

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

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; 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; Selective Serotonin Reuptake Inhibitors; Fluvoxamine; BI 409306
• Other Study ID Numbers: 1289.35; 2016-000752-10 (EudraCT Number: EudraCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD 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. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to:

https://www.mystudywindow.com/msw/datatransparency

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No