Evaluation of Safety and Tolerability of BI 894416 in Patients With Mild Asthma

NCT03971539 | Completed Phase 1 Results

• 2 other identifiers: 1371-00082019-000805-60
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

In both parts, the primary comparisons of interest are between the percentage of patients with drug-related adverse events at each dose and placebo during single and multiple dosing regimens. Based on these, the primary trial objective is to assess safety and tolerability of BI 894416 at each dose. Secondary measures of interest are the geometric means of BI 894416 plasma AUC0-∞ and Cmax after single dose in SRD part and AUC0-8 and Cmax after single dose as well as AUCτ,ss and Cmax,ss after 7 days multiple dosing in MRD part. The objective is to assess the pharmacokinetics of BI 894416 following single and multiple administration.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Treatment-emergent Adverse Events Related to BI 894416

  Percentage of patients with treatment-emergent adverse events (AEs) related to BI 894416.

  From start of treatment till the end of trial, up to 30 days.

Secondary Outcomes (7)

• AUC0-∞ (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) of BI 894416 (SRD Part)

  3 hours before and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72 and 96 hours following treatment.

• Cmax (Maximum Measured Concentration of the Analyte in Plasma) of BI 894416 (SRD Part)

  3 hours before and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72 and 96 hours following treatment.

• AUC0-8 (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 8 Hours) of BI 894416 After the First Dose (MRD Part)

  5 minutes before and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours following first dose (day 1).

• Cmax (Maximum Measured Concentration of the Analyte in Plasma) of BI 894416 After the First Dose (MRD Part)

  5 minutes before and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 23.92 hours following first dose (day 1).

• AUCtau,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State) of BI 894416 After the Last Dose (MRD Part)

  5 minutes before and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 96 hours following last dose (day 9).

Study Arms (9)

SRD part: Placebo

PLACEBO COMPARATOR

Single rising dose (SRD) part: Placebo film-coated tablet matching BI 894416 taken once orally with 240 milliliter of water after an overnight fast of at least 10 hours.

Drug: Placebo

SRD part: 75 mg BI 894416

EXPERIMENTAL

Single rising dose (SRD) part: 75 milligram (mg) BI 894416 film-coated tablet taken once orally with 240 milliliter of water after an overnight fast of at least 10 hours.

Drug: BI 894416; Drug: Placebo

SRD part: 125 mg BI 894416

EXPERIMENTAL

Single rising dose (SRD) part: 125 milligram (mg) BI 894416 film-coated tablet taken once orally with 240 milliliter of water after an overnight fast of at least 10 hours.

Drug: BI 894416

SRD part: 170 mg BI 894416

EXPERIMENTAL

Single rising dose (SRD) part: 170 milligram (mg) BI 894416 film-coated tablet taken once orally with 240 milliliter of water after an overnight fast of at least 10 hours.

Drug: BI 894416

MRD part: Placebo

PLACEBO COMPARATOR

Multiple rising dose (MRD) part: Placebo film-coated tablet matching BI 894416 taken for 9 days orally with 240 milliliter of water. Administration of Placebo at Day 1 and Day 9 once daily in the morning (q.d.) and at Day 2 to Day 8 three times daily at an interval of 8 hours (t.i.d.). Morning dose to be taken after an overnight fast of at least 10 hours, afternoon dose to be taken after fasting for 2 hours.

Drug: Placebo

MRD part: 10 mg BI 894416

EXPERIMENTAL

Multiple rising dose (MRD) part: 10 milligram (mg) BI 894416 film-coated tablet taken for 9 days orally with 240 milliliter of water. Administration of BI 894416 at Day 1 and Day 9 once daily in the morning (q.d.) and at Day 2 to Day 8 three times daily at an interval of 8 hours (t.i.d.). Morning dose to be taken after an overnight fast of at least 10 hours, afternoon dose to be taken after fasting for 2 hours.

Drug: BI 894416

MRD part: 25 mg BI 894416

EXPERIMENTAL

Multiple rising dose (MRD) part: 25 milligram (mg) BI 894416 film-coated tablet taken for 9 days orally with 240 milliliter of water. Administration of BI 894416 at Day 1 and Day 9 once daily in the morning (q.d.) and at Day 2 to Day 8 three times daily at an interval of 8 hours (t.i.d.). Morning dose to be taken after an overnight fast of at least 10 hours, afternoon dose to be taken after fasting for 2 hours.

Drug: BI 894416

MRD part: 50 mg BI 894416

EXPERIMENTAL

Multiple rising dose (MRD) part: 50 milligram (mg) BI 894416 film-coated tablet taken for 9 days orally with 240 milliliter of water. Administration of BI 894416 at Day 1 and Day 9 once daily in the morning (q.d.) and at Day 2 to Day 8 three times daily at an interval of 8 hours (t.i.d.). Morning dose to be taken after an overnight fast of at least 10 hours, afternoon dose to be taken after fasting for 2 hours.

Drug: BI 894416

MRD part: 60 mg BI 894416

EXPERIMENTAL

Multiple rising dose (MRD) part: 60 milligram (mg) BI 894416 film-coated tablet taken for 9 days orally with 240 milliliter of water. Administration of BI 894416 at Day 1 and Day 9 once daily in the morning (q.d.) and at Day 2 to Day 8 three times daily at an interval of 8 hours (t.i.d.). Morning dose to be taken after an overnight fast of at least 10 hours, afternoon dose to be taken after fasting for 2 hours.

Drug: BI 894416

Interventions

BI 894416 DRUG

BI 894416 film-coated tablet.

MRD part: 10 mg BI 894416; MRD part: 25 mg BI 894416; MRD part: 50 mg BI 894416; MRD part: 60 mg BI 894416; SRD part: 125 mg BI 894416; SRD part: 170 mg BI 894416; SRD part: 75 mg BI 894416

Placebo DRUG

Placebo film-coated tablet matching BI 894416.

MRD part: Placebo; SRD part: 75 mg BI 894416; SRD part: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. Medication washout and medication restrictions according to protocol are allowed only after informed consent is obtained.
• Male patients aged at least 18 years but not more than 55 years at the time of informed consent.
• Men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
• Pre-bronchodilator clinic measured FEV1 of ≥ 70% of predicted normal at the screening visit (Visit 1). Calculations will be based on Global Lung Function Initiative (GLI) formula
• A diagnosis of asthma, diagnosed by a physician.
• Patients should be non-smokers or ex-smokers who stopped smoking at least 12 weeks prior to screening and are expected to be able to not smoke for the duration of the study.
• Patients must be able to perform all trial related procedures including pulmonary function tests, nasal brushings.
• BMI of 18.5 to 32 kg/m2 (incl.)
• For MRD part: Patients are allowed to be on stable inhaled low dose corticosteroid (please refer to GINA guidelines) for at least 4 weeks prior to screening.

You may not qualify if:

• Any finding in the medical examination (including BP, PR, echocardiography and echocardiography stress test or ECG and including the neurological examination) is deviating from normal and judged 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 50 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 judged as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular (stress), 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 other than BI 894416 has been administered within 60 days or 5 half-lives (whichever is greater) prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug. In case of planned participation in the MRD part in this trial the previous participation in one dose group of the SRD part is allowed if BI 894416 has been administered more than 21 days prior to planned administration of BI 894416 in the MRD part. (Participation in an SRD dose group after the patient has participated in the MRD part is not allowed.)
• Alcohol abuse (consumption of more than 24 g per day)
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Fraunhofer ITEM

Hanover, 30625, Germany

Location

Related Links

• Related Info

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Limitations and Caveats

The planned last two dose level in the single rising dose (SRD) part and the last dose in the multiple rising dose (MRD) part were not used as the predicted exposure exceeded the limits predefined in the clinical trial protocol.

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: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2019
• First Posted: June 3, 2019
• Study Start: July 15, 2019
• Primary Completion: October 26, 2020
• Study Completion: October 26, 2020
• Last Updated: August 21, 2023
• Results First Posted: August 21, 2023

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)