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

NCT03979820 | Terminated Phase 1 Results

• 2 other identifiers: 1386.162018-003965-32
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• 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.

  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).

Study Arms (4)

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

Interventions

BI 1467335 DRUG

Film-coated tablet

10 mg BI 1467335/10 mg BI 1467335 + Tyramine; 15 mg BI 1467335/15 mg BI 1467335 + Tyramine

Placebo DRUG

Film-coated tablet

Placebo/Placebo + Tyramine

Phenelzine sulfate DRUG

Film-coated tablet

Phenelzine/Phenelzine + Tyramine

Tyramine DRUG

Capsules

10 mg BI 1467335/10 mg BI 1467335 + Tyramine; 15 mg BI 1467335/15 mg BI 1467335 + Tyramine; Phenelzine/Phenelzine + Tyramine; Placebo/Placebo + Tyramine

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

PRA Health Sciences Onderzoekscentrum Martini

Groningen, 9728 NZ, Netherlands

Location

Related Links

• Related Info

MeSH Terms

Interventions

Phenelzine; Tyramine

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Biogenic Monoamines; Biogenic Amines; Amines

Limitations and Caveats

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.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: June 7, 2019
• Study Start: July 31, 2019
• Primary Completion: April 8, 2020
• Study Completion: April 8, 2020
• Last Updated: June 4, 2021
• Results First Posted: June 4, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)