A Study to Test How Well Healthy Men and Women Tolerate Different Doses of BI 706321

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Midazolam; Drug: Placebo; Drug: BI 703621

Study type: Interventional

Funder types: Industry

Identifiers

NCT04241458

2019-004351-36 (EudraCT Number)

1425-0002

Details and patient eligibility

About

The main objectives of this trial are to investigate safety, tolerability and pharmacokinetics (PK) of BI 706321 in healthy male and female subjects following oral administration of multiple rising doses for 14 days.

Enrollment: 39 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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), temperature), 12-lead electrocardiogram (ECG), and clinical laboratory tests
• Age of 18 to 55 years (inclusive, at screening)
• Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive, at screening)
• Signed and dated written informed consent prior to admission to the study, in accordance with GCP and local legislation

Exclusion criteria

• Any finding in the medical examination (including BP, PR, temperature or 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 45 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
• 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 30 days (or 5 half-lives (whichever longer)) of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered
• Smoker of more than 10 cigarettes or 3 cigars or 3 pipes per day
• Inability to refrain from smoking while in-house stay
• Alcohol abuse (consumption of more than 20 g per day for females and 30 g per day for males), and unwillingness/inability to refrain from intake of alcoholic beverages from 48 hours prior to the trial medication administration and until Day 7 post trial medication administration.
• 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
• ALT (alanine transaminase), AST (aspartate transaminase), or creatinine exceed upper limit of normal range at screening, confirmed by a repeat test
• hemoglobin (Hb), platelets and neutrophils below lower limit of normal range at screening, confirmed by a repeat test
• Positive result for human immunoinsufficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection at screening.
• History of tuberculosis (TB) or positive finding in interferon-gamma release assay (IGRA).

Female subjects will not be allowed to participate, if any of the following apply:

• Not surgically sterilised or not postmenopausal, defined as at least 1 year of spontaneous amenorrhea without an alternative medical cause (in questionable cases a blood sample with simultaneous levels of FSH above 30 U/L and estradiol below 20 ng/L is confirmatory)
• Positive pregnancy test
• Lactation

Male subjects will not be allowed to participate, if any of the following apply:

- Male subjects with women of childbearing potential (WOCBP) partner who are unwilling to use male contraception (condom or sexual abstinence) from time point of administration of trial medication until 30 days thereafter. Sperm donation is not allowed from the time point of drug administration until 30 days thereafter.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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39 participants in 5 patient groups, including a placebo group

2 mg BI 706321

Experimental group

Description:

Subjects were orally administered a single daily dose of 2 x 1 capsule of 1 milligrams (mg) of BI 706321 on Day 1 and from Day 6 to 19. The trial medication was administered with about 240 millilitres (mL) of water after an overnight fast of at least 10 hours (h).

Treatment:

Drug: BI 703621

5 mg BI 706321

Experimental group

Description:

Subjects were orally administered a single daily dose of 1 capsule of 5 milligrams (mg) of BI 706321 on Day 1 and from Day 6 to 19. The trial medication was administered with about 240 millilitres (mL) of water after an overnight fast of at least 10 hours (h).

Treatment:

Drug: BI 703621

8 mg BI 706321 + 75 ug midazolam

Experimental group

Description:

Subjects were orally administered a single daily dose of 1 capsule of 5 milligrams (mg) and 3 capsules of 1 mg of BI 706321 on Day 1 and from Day 6 to 19. Subjects were also orally administered a single daily dose of 1.5 millilitres (mL) (75 micrograms) of Midazolam solution on Day -1 and Day 19. The trial medication was administered with about 240 mL of water after an overnight fast of at least 10 hours (h).

Treatment:

Drug: BI 703621

Drug: Midazolam

10 mg BI 706321+ 75 ug midazolam

Experimental group

Description:

Subjects were orally administered a single daily dose of 2 capsules of 5 milligrams (mg) of BI 706321 on Day 1 and from Day 6 to 19. Subjects were also orally administered a single daily dose of 1.5 millilitres (mL) (75 micrograms) of Midazolam solution on Day -1 and Day 19. The trial medication was administered with about 240 mL of water after an overnight fast of at least 10 hours (h).

Treatment:

Drug: BI 703621

Drug: Midazolam

Placebo

Placebo Comparator group

Description:

Subjects were orally administered a single daily dose of matching placebo to BI 706321 capsules on Day 1 and from Day 6 to 19. Three out of the seven subjects were also orally administered a single daily dose of 1.5 millilitres (mL) (75 micrograms) of Midazolam solution on Day -1 and Day 19. The trial medication was administered with about 240 millilitres (mL) of water after an overnight fast of at least 10 hours (h).

Treatment:

Drug: Placebo