- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03979820
A Study in Healthy People to Test How Combining BI 1467335 and Tyramine Affects Blood Pressure
A Phase I Parallel Group Study in Healthy Subjects to Evaluate the Effect of Multiple Oral Doses of BI 1467335 and Phenelzine as Positive Control on Blood Pressure Response to Oral Tyramine (Double-blind, Randomised, Placebo-controlled Design for BI 1467335 Treatment Groups, Open Label for Phenelzine)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Groningen, Netherlands, 9728 NZ
- PRA Health Sciences Onderzoekscentrum Martini
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Healthy male or female 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
- Age of 18 to 45 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
Male subjects, or female subjects who meet any of the following criteria before the first administration of trial medication until 30 days after trial completion:
- Use of adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral or vaginal contraceptives, intrauterine device (in case of oral contraceptives start of contraception at least 30 days before administration of trial medication)
- Sexually abstinent
- A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
- Surgically sterilised (including hysterectomy)
- Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with levels of FSH above 33,4 U/L and estradiol below 71,6 pmol/L is confirmatory) Alternatively, true abstinence is acceptable when it is in line with the subject's preferred and usual lifestyle. If a subject is usually not sexually active but becomes active, with their partner, they must comply with the contraceptive requirements detailed above.
Exclusion Criteria:
- Any finding in the medical examination (including Blood pressure (BP), Pulse rate (PR) or Electrocardiogram (ECG)) 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 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 assessed as clinically relevant by the investigator
- 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 (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 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 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 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 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
- Use of monoamine oxidase (MAO) inhibitors within 90 days before tyramine dosing
- Use of fluoxetine within 5 weeks before tyramine dosing
- Use of over-the-counter sympathomimetic or grapefruit products within 7 days before tyramine dosing
- Subject has a known intolerability to tyramine-containing foods
- At screening, no increase of systolic blood pressure > 30 mmHg during tyramine challenge at the highest tested dose of 700 mg tyramine
Female subjects will not be allowed to participate, if any of the following apply:
- Positive pregnancy test, pregnancy, or plans to become pregnant within 30 days after study completion
- Lactation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 10 mg BI 1467335/10 mg BI 1467335 + Tyramine
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Film-coated tablet
Capsules
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Experimental: 15 mg BI 1467335/15 mg BI 1467335 + Tyramine
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Film-coated tablet
Capsules
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Active Comparator: Phenelzine/Phenelzine + Tyramine
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Capsules
Film-coated tablet
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Placebo Comparator: Placebo/Placebo + Tyramine
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Film-coated tablet
Capsules
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tyramine Sensitivity Factor (TSF)
Time Frame: At baseline (Day -11 up to Day-2) and at steady state (Day 29 up to Day 39 for the "Placebo/Placebo + Tyramine" and "10 mg BI 1467335/10 mg BI 1467335 + Tyramine" arms, Day 8 up to Day 19 for the "Phenelzine/ Phenelzine + Tyramine" arm).
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TSF was defined as ratio of the tyramine dose causing an increase of systolic blood pressure (SBP) ≥ 30 millimetre of mercury (mmHg) for at least 3 consecutive measurements (TYR30) at baseline and at steady state of BI 1467335, placebo or phenelzine.
Geometric Mean is the Geometric Least Squares Mean and is extracted from the ANOVA model that includes all treatments.
Standard error is the geometric standard error of the mean (gSE) and is extracted from the ANOVA model that includes all treatments.
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At baseline (Day -11 up to Day-2) and at steady state (Day 29 up to Day 39 for the "Placebo/Placebo + Tyramine" and "10 mg BI 1467335/10 mg BI 1467335 + Tyramine" arms, Day 8 up to Day 19 for the "Phenelzine/ Phenelzine + Tyramine" arm).
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Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Antidepressive Agents
- Monoamine Oxidase Inhibitors
- Sympathomimetics
- Adrenergic Uptake Inhibitors
- Phenelzine
- Tyramine
Other Study ID Numbers
- 1386.16
- 2018-003965-32 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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, 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). For more details refer to: http://trials.boehringer-ingelheim.com/
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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