HealthyPhase 1NCT03979820

A Study in Healthy People to Test How Combining BI 1467335 and Tyramine Affects Blood Pressure

A Phase 1 study testing BI 1467335, Phenelzine sulfate and Tyramine in people with Healthy, run by Boehringer Ingelheim at 1 site in Netherlands.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The main objective of the study is investigate the effect of escalating doses of oral tyramine on systolic blood pressure (SBP) at baseline and following an oral treatment with BI 1467335 up to 39 days at a low or high dose once daily compared to placebo and phenelzine (Nardil®) as positive control. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: BI 1467335, Phenelzine sulfate and Tyramine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 53 participants
Where: 1 siteNetherlands
Study dates: 31 Jul 2019to 8 Apr 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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)

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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.

Who cannot join

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)

Show all 30Show fewer

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

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

PRA Health Sciences Onderzoekscentrum Martini
Groningen, 9728 NZ

Other trials in Netherlands

About this study

Official title: 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)

Conditions: Healthy
Being tested: BI 1467335, Placebo, Phenelzine sulfate, Tyramine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BI 1467335Drug
Film-coated tablet
PlaceboDrug
Film-coated tablet
Phenelzine sulfateDrug
Film-coated tablet
TyramineDrug
Capsules

Study groups in NCT03979820
Study group	Role	What they receive
10 mg BI 1467335/10 mg BI 1467335 + Tyramine	Experimental	Not described Receives: Drug: BI 1467335; Drug: Tyramine
15 mg BI 1467335/15 mg BI 1467335 + Tyramine	Experimental	Not described Receives: Drug: BI 1467335; Drug: Tyramine
Phenelzine/Phenelzine + Tyramine	Active comparator	Not described Receives: Drug: Phenelzine sulfate; Drug: Tyramine
Placebo/Placebo + Tyramine	Placebo comparator	Not described Receives: Drug: Placebo; Drug: Tyramine

What is being measured

The primary outcome is the main question the study is designed to answer.

Tyramine Sensitivity Factor (TSF)
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.
Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Jul 20198 Apr 2020

First posted7 Jun 2019
Study start31 Jul 2019
Primary completion8 Apr 2020
Study completion8 Apr 2020

Why it stopped: Study discontinued - testing of highest dose obsolete

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 53 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03979820
Sponsor's protocol ID: 1386.16
Other IDs: 2018-003965-32, 2018
Status last verified: Mar 2021
First submitted: 6 Jun 2019
Last updated: 4 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: 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/

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 4 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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)
ClinicalTrials.gov ID: NCT03979820
Acronym / sponsor ID: 1386.16
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study discontinued - testing of highest dose obsolete
Enrolment: 53 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 31 Jul 2019 (actual)
Primary completion: 8 Apr 2020 (actual)
Study completion: 8 Apr 2020 (actual)
First posted: 7 Jun 2019 (actual)
Results: Posted 4 Jun 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
10 mg BI 1467335/10 mg BI 1467335 + Tyramine	Experimental	Drug: BI 1467335, Drug: Tyramine
15 mg BI 1467335/15 mg BI 1467335 + Tyramine	Experimental	Drug: BI 1467335, Drug: Tyramine
Phenelzine/Phenelzine + Tyramine	Active comparator	Drug: Phenelzine sulfate, Drug: Tyramine
Placebo/Placebo + Tyramine	Placebo comparator	Drug: Placebo, Drug: Tyramine

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (10 listed)

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:

Key exclusion criteria (30 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BI 1467335Film-coated tablet	Drug	10 mg BI 1467335/10 mg BI 1467335 + Tyramine, 15 mg BI 1467335/15 mg BI 1467335 + Tyramine
PlaceboFilm-coated tablet	Drug	Placebo/Placebo + Tyramine
Phenelzine sulfateFilm-coated tablet	Drug	Phenelzine/Phenelzine + Tyramine
TyramineCapsules	Drug	10 mg BI 1467335/10 mg BI 1467335 + Tyramine, 15 mg BI 1467335/15 mg BI 1467335 + Tyramine, Phenelzine/Phenelzine + Tyramine, Placebo/Placebo + Tyramine

Primary outcome

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).
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.

Results and safety

Results posted to the registry on 4 Jun 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo/Placebo + Tyramine	13	7
Phenelzine/Phenelzine + Tyramine	14	14
10 mg BI 1467335/10 mg BI 1467335 + Tyramine	16	15
15 mg BI 1467335/15 mg BI 1467335 + Tyramine	10	0

Primary outcome: 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).. Geometric least squares mean (Standard Error). Unit: Ratio of tyramine dose

Measure	Placebo/Placebo + Tyramine n = 7	Phenelzine/Phenelzine + Tyramine n = 14	10 mg BI 1467335/10 mg BI 1467335 + Tyramine n = 14
Value	0.98 (1.25)	5.31 (1.17)	1.20 (1.17)

Placebo/Placebo + Tyramine vs Phenelzine/Phenelzine + Tyramine: Ratio of geometric mean TSFs: 544.36 (90% CI 340.57 to 870.09), ANOVA
Placebo/Placebo + Tyramine vs 10 mg BI 1467335/10 mg BI 1467335 + Tyramine: Ratio of geometric mean TSFs: 123.22 (90% CI 77.09 to 196.95), ANOVA

Population analysed: Per protocol analysis set (PPS): This analysis set included all participants in the TS who provided at least one endpoint that was defined as primary and was not excluded due to a protocol violation relevant. Descriptive and model-based analyses of the primary endpoint were based on the PPS. Participants of the arms "15 mg BI 1467335/15 mg BI 1467335 + Tyramine" and "Placebo/Placebo + Tyramine" who could not complete the tyramine steady state challenge were excluded from the analysis.

Adverse events

Time frame: Tyramine screening: From Day -11 to time of first administration of BI 1467335, placebo or phenelzine Day 1, up to 11 days. Placebo, 10 mg BI 1467335, 15 mg BI 1467335: From Day 1 to Day 29, up to 28 days. Phenelzine: From Day 1 to Day 8, up to 7 days. Placebo + Tyramine, 10 mg BI 1467335 + Tyramine, 15 mg BI 1467335 + Tyramine: From Day 29 up to End of trial (EoT), up to 23 days. Phenelzine +Tyramine: From Day 8 until EoT, up to 24 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tyramine Screening	0 of 53 (0%)	39 of 53 (73.6%)	0 of 53
Placebo	0 of 13 (0%)	9 of 13 (69.2%)	0 of 13
Phenelzine	0 of 14 (0%)	11 of 14 (78.6%)	0 of 14
10 mg BI 1467335	0 of 16 (0%)	8 of 16 (50%)	0 of 16
15 mg BI 1467335	0 of 10 (0%)	7 of 10 (70%)	0 of 10
Placebo + Tyramine	0 of 9 (0%)	8 of 9 (88.9%)	0 of 9
Phenelzine + Tyramine	0 of 14 (0%)	14 of 14 (100%)	0 of 14
10 mg BI 1467335 + Tyramine	1 of 15 (6.7%)	10 of 15 (66.7%)	0 of 15
15 mg BI 1467335 + Tyramine	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6

Limitations and caveats (from the sponsor): The sponsor decided to permanently discontinue the trial on 14 April 2020 due to lock down of the trial site enforced by the Covid-19 pandemic. Therefore some of the planned analysis were not performed due to lack of data.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: No. 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/

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BI 1467335, Phenelzine sulfate and Tyramine in people with Healthy, run by Boehringer Ingelheim at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03979820.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2021.