A Study in Healthy Men and Women to Test How Well Different Doses of BI 1323495 Are Tolerated

NCT04107805 | Completed Phase 1 Results

• 2 other identifiers: 1405-00022018-004238-13
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this trial is to investigate the safety and tolerability of BI 1323495 in healthy subjects following bid oral administration of multiple rising doses, each over an 11 day treatment period. Secondary objectives are the exploration of the pharmacokinetics (PK) including dose proportionality (only for Part 1) as well as attainment of steady state. This includes exploration of a therapeutic exposure range, a range not adequately achieved in the single-rising dose trial 1405-0001.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Treatment-emergent Drug-related Adverse Events (AEs)

  Percentage of participants with treatment-emergent drug-related Adverse Events (AEs) is reported. Percentages are calculated using total number of subjects per treatment as the denominator.

  Midazolam alone: From administration of midazolam on Day -1 until first administration of BI 1323495 on Day 1, up to 24 hours. All others: From first administration until 7 days after the last administration of BI 1323495, up to 18 days.

Secondary Outcomes (5)

• Area Under the Concentration-time Curve of BI 1323495 in Plasma Over a Time Interval of 12 h After Administration of the First Dose (AUC0-12)

  Within 3 hours before and 20 minutes (min), 40 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, and 12h after the first administration of BI 1323495 on Day 1.

• Only for Once Daily (qd) Dosing Group: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over a Uniform Dosing Interval of 24 h After Administration of the First Dose (AUC0-24)

  Within 3 hours before and 20 minutes (min), 40 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24 h after administration of BI 1323495 on Day 1.

• Maximum Measured Concentration of BI 1323495 in Plasma After the First Dose (Cmax)

  Within 3 hours before and 20 minutes (min), 40 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24h* after the first administration of BI 1323495 on Day 1. * Applicable only for the 120 mg BI 1323495 qd EM arm.

• Area Under the Concentration-time Curve of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss)

  Within 3 hours before and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24h* after the last administration of BI 1323495 on Day 11. * Applicable only for the 120 mg BI 1323495 qd EM arm.

• Maximum Measured Concentration of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)

  Within 3 hours before and 20 min, 40 min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24h* after the last drug administration of BI 1323495 on Day 11. * Applicable only for the 120 mg BI 1323495 qd EM arm.

Study Arms (9)

10 mg BI 1323495 bid EM

EXPERIMENTAL

Drug: BI 1323495

10 mg BI 1323495 bid PM

EXPERIMENTAL

Drug: BI 1323495

30 mg BI 1323495 bid EM

EXPERIMENTAL

Drug: BI 1323495

30 mg BI 1323495 bid PM

EXPERIMENTAL

Drug: BI 1323495

70 mg BI 1323495 bid + Midazolam EM

EXPERIMENTAL

Drug: BI 1323495; Drug: Midazolam

120 mg BI 1323495 bid + Midazolam EM

EXPERIMENTAL

Drug: BI 1323495; Drug: Midazolam

120 mg BI 1323495 qd EM

EXPERIMENTAL

Drug: BI 1323495

150 mg BI 1323495 bid + Midazolam EM

EXPERIMENTAL

Drug: BI 1323495; Drug: Midazolam

Placebo/Placebo+ Midazolam

EXPERIMENTAL

Drug: Placebo; Drug: Midazolam

Interventions

BI 1323495 DRUG

Tablet

10 mg BI 1323495 bid EM; 10 mg BI 1323495 bid PM; 120 mg BI 1323495 bid + Midazolam EM; 120 mg BI 1323495 qd EM; 150 mg BI 1323495 bid + Midazolam EM; 30 mg BI 1323495 bid EM; 30 mg BI 1323495 bid PM; 70 mg BI 1323495 bid + Midazolam EM

Placebo DRUG

Tablet

Placebo/Placebo+ Midazolam

Midazolam DRUG

Oral administration

120 mg BI 1323495 bid + Midazolam EM; 150 mg BI 1323495 bid + Midazolam EM; 70 mg BI 1323495 bid + Midazolam EM; Placebo/Placebo+ Midazolam

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (Blood Pressure (BP), PR), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
• Age of 18 to 70 years (inclusive)
• 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
• For Part I: Subjects genotyped as UGT2B17 extensive metabolizers, i.e., carrying at least one functional allele of the UGT2B17 gene (\*1/\*1 or \*1/\*2).
• For Part II: Subjects genotyped as UGT2B17 poor metabolizers, i.e., carrying no functional allele of the UGT2B17 gene (\*2/\*2)
• Male or female subjects:
• For 'female subjects not of childbearing potential' at least one of the following criteria must be fulfilled:
• Permanently sterile (permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy)
• Postmenopausal, defined as at least 1 year of spontaneous amenorrhea without an alternative medical cause (in questionable cases a blood sample with FSH above 40 U/L and estradiol below 30 ng/L is confirmatory)
• Female subjects of childbearing potential must use a highly effective contraception method from at least 30 days before the first administration of trial medication until 14 days after trial completion

You may not qualify if:

• Any finding in the medical examination (including Blood Pressure (BP), PR, or Electrocardiogram (ECG)) deviating from normal and assessed as clinically relevant by the investigator. In particular 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) at screening
• 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; safety laboratory screening evaluation can be repeated a maximum of two times
• Any evidence of a concomitant disease assessed as clinically relevant by the investigator or at risk of requiring concomitant drug therapy, e.g., gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorder, 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 cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients); mild seasonal allergy adequately managed by topic administration of drugs to eyes or nose is not excluded
• Subjects with a documented active malignancy, or malignancy for which the subject has undergone resection, radiation therapy, or drug therapy (e.g., cytostatic, protein kinase inhibitor, or immune checkpoint inhibitor therapy), within the last 5 years.
• Subjects who have been previously randomised in this study.
• 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, or within 5 half-lives of the investigational drug (whichever is longer), of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered
• Major surgery (major according to the investigator's assessment) performed within 6 weeks prior to randomisation or planned within 3 months after screening, e.g. hip replacement.
• Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day), also inability to refrain from smoking during in-house confinement
• Alcohol abuse (consumption of more than 20 g per day for females and 30 g per day for males) or any other 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Fraunhofer ITEM

Hanover, 30625, Germany

Location

Related Links

• Related Info

MeSH Terms

Interventions

Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2019
• First Posted: September 27, 2019
• Study Start: November 4, 2019
• Primary Completion: March 5, 2021
• Study Completion: March 26, 2021
• Last Updated: February 22, 2024
• Results First Posted: February 22, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)