Healthy
Conditions
Brief summary
The main objective of this trial is to select a formulation principle (tablet vs. capsule) and to optimize the identified extended release formulation of BI 894416, if needed.
Interventions
DRUGBI 894416 Reference Formulation
R1 - 60 milligram (6 x 10 milligram tablets) BI 894416 Reference Formulation, immediate release (IR) tablets taken orally with 240 mL of water after an overnight fast of at least 10 hours.
DRUGBI 894416 Formulation A2
T1 - One single dose of 62.5 milligram (1 tablet) BI 894416 Formulation A2, extended release (ER) tablet (fast release rate, FRR) taken orally with 240 mL of water after an overnight fast of at least 10 hours.
DRUGBI 894416 Formulation C2
T2 - One single dose of 62.5 milligram (1 tablet) BI 894416 Formulation C2, extended release (ER) tablet (slow release rate, SRR) taken orally with 240 mL of water after an overnight fast of at least 10 hours. and T5 - One single dose of 62.5 milligram (1 tablet) BI 894416 Formulation C2, extended release (ER) tablet (slow release rate, SRR) taken orally with 240 mL of water following a high-fat high-calorie breakfast.
DRUGBI 894416 Formulation D2
T3 - One single dose of 62.5 milligram (1 capsule) BI 894416 Formulation D2, extended release (ER) capsule (fast release rate, FRR) taken orally with 240 mL of water after an overnight fast of at least 10 hours.
DRUGBI 894416 Formulation F2
T4 - One single dose of 62.5 milligram (1 capsule) BI 894416 Formulation F2, extended release (ER) capsule (slow release rate, SRR) taken orally with 240 mL of water after an overnight fast of at least 10 hours. and T6 - One single dose of 62.5 milligram (1 capsule) BI 894416 Formulation F2, extended release (ER) capsule (slow release rate, SRR) taken orally with 240 mL of water following a high-fat high-calorie breakfast.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male 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 tests * Age of 18 to 55 years (inclusive) at the time of signing informed consent * Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive) as measured at screening * Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation * Subjects who are sexually active must use, with their partner, highly effective contraception from the time of administration of trial medication until 30 days after administration of trial medication. Adequate methods are: * Condoms plus use of hormonal contraception by the female partner that started at least 2 months prior to administration of trial medication (e.g., implants, injectables, combined oral or vaginal contraceptives, intrauterine device) or * Condoms plus surgical sterilization (vasectomy at least 1 year prior to enrolment) or * Condoms plus surgically sterilised partner (including hysterectomy) or * Condoms plus intrauterine device or * Condoms plus partner of non-childbearing potential (including homosexual men) Subjects are required to use condoms to prevent unintended exposure of the partner (both, male and female) to the study drug via seminal fluid. Male subjects should use a condom throughout the study and for 30 days after last Investigational Medicinal Product (IMP) administration. 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 Male subjects should not donate sperm for the duration of the study and for at least 30 days after last IMP administration
Exclusion criteria
* Any finding in the medical examination (including Blood pressure (BP), Pulse rate (PR), Electrocardiogram (ECG), physical and neurological examination) 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 40 to 90 mmHg, or pulse rate outside the range of 40 to 100 bpm at screening and pre-dose of first period * 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). Inactive hayfever is permitted. * 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 90 days of planned first administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered * Smoker (unless the subject quit smoking for at least 3 months prior to first planned administration of trial medication) as demonstrated by a positive urine cotinine test; this includes also the use of e-cigarettes and nicotine replacement products * Alcohol abuse (consumption of more than 21 units per week) or positive alcohol breath test * 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) or any other relevant ECG finding at screening and predose * 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 * History of relevant neurological disorder affecting the peripheral or central nervous system (this includes but is not limited to: stroke, epilepsy, inflammatory or atrophic diseases affecting the nervous system, cluster headache or any cancer of the nervous system). Febrile seizures in childhood or adolescence, recovered carpal tunnel syndrome, recovered uncomplicated meningitis, recovered herpes zoster, tension headache, occasional benign tics (e.g. due to stress) or minor par- or dysesthesia (e.g. as a side effect of prior blood withdrawal) do not constitute a history of relevant neurological disorder. * History of immunological disease, except allergy not relevant to the trial (such as mild hay fever or dust mite allergy) and except asthma in childhood or adolescence * History of cancer (other than successfully treated basal cell carcinoma) * Liver enzymes (ALT, AST, GGT, AP) above upper limit of normal at the screening examination * Within 10 days prior to administration of trial medication, use of any drug that could reasonably inhibit platelet aggregation or coagulation (e.g., acetylsalicylic acid) * Male subjects with Woman of child bearing potential (WOCBP) partner who are unwilling to use male contraception (condom or sexual abstinence) from time point of first administration of trial medication until 30 days after the last administration of trial medication * Subjects with pregnant or lactating partners
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours before and 0.33, 0.66, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24, 34, 48, 58 and 72 hours following drug administration. | Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours before and 0.33, 0.66, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24, 34, 48, 58 and 72 hours following drug administration. | Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). |
Countries
United Kingdom
Participant flow
Recruitment details
Formulation selection and subsequent optimization of two different oral formulations of BI 894416 in healthy male subjects (open-label, randomised, single-dose study in two parts; trial part 1: five-period crossover design with an additional sixth period in a fixed sequence; (optional) trial part 2: three-period crossover followed by a two-period crossover design), trial part 2 was not performed.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| T3-R1-T1-T4-T2-T5 (Sequence I+T5) Sequence I+T5, with treatments in the following order: T3-R1-T1-T4-T2-T5 with a washout period of at least 4 days between treatments. All test treatments (T1-T6) were one single dose of 62.5 milligram. R1 and T1-T4: taken orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. T5-T6: taken orally with 240 mL of water following a high-fat high-calorie breakfast.
Reference (R1): 60 milligram (mg) (6 x 10 mg tablets) BI 894416 Reference Formulation, immediate release (IR) tablets.
Test 1 (T1): 1 tablet BI 894416 Formulation A2, extended release (ER) tablet (fast release rate, FRR).
Test 2 (T2): 1 tablet BI 894416 Formulation C2, ER tablet (slow release rate, SRR).
Test 3 (T3): 1 capsule BI 894416 Formulation D2, ER capsule (FRR). Test 4 (T4): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). Test 5 (T5): 1 tablet BI 894416 Formulation C2, ER tablet (SRR). Test 6 (T6): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). | 2 |
| T3-R1-T1-T4-T2-T6 (Sequence I+T6) Sequence I+T6, with treatments in the following order: T3-R1-T1-T4-T2-T6 with a washout period of at least 4 days between treatments. All test treatments (T1-T6) were one single dose of 62.5 milligram. R1 and T1-T4: taken orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. T5-T6: taken orally with 240 mL of water following a high-fat high-calorie breakfast.
Reference (R1): 60 milligram (mg) (6 x 10 mg tablets) BI 894416 Reference Formulation, immediate release (IR) tablets.
Test 1 (T1): 1 tablet BI 894416 Formulation A2, extended release (ER) tablet (fast release rate, FRR).
Test 2 (T2): 1 tablet BI 894416 Formulation C2, ER tablet (slow release rate, SRR).
Test 3 (T3): 1 capsule BI 894416 Formulation D2, ER capsule (FRR). Test 4 (T4): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). Test 5 (T5): 1 tablet BI 894416 Formulation C2, ER tablet (SRR). Test 6 (T6): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). | 2 |
| T2-T1-T3-R1-T4-T5 (Sequence II+T5) Sequence II+T5, with treatments in the following order: T2-T1-T3-R1-T4-T5with a washout period of at least 4 days between treatments. All test treatments (T1-T6) were one single dose of 62.5 milligram. R1 and T1-T4: taken orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. T5-T6: taken orally with 240 mL of water following a high-fat high-calorie breakfast.
Reference (R1): 60 milligram (mg) (6 x 10 mg tablets) BI 894416 Reference Formulation, immediate release (IR) tablets.
Test 1 (T1): 1 tablet BI 894416 Formulation A2, extended release (ER) tablet (fast release rate, FRR).
Test 2 (T2): 1 tablet BI 894416 Formulation C2, ER tablet (slow release rate, SRR).
Test 3 (T3): 1 capsule BI 894416 Formulation D2, ER capsule (FRR). Test 4 (T4): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). Test 5 (T5): 1 tablet BI 894416 Formulation C2, ER tablet (SRR). Test 6 (T6): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). | 2 |
| T2-T1-T3-R1-T4-T6 (Sequence II+T6) Sequence II+T6, with treatments in the following order: T2-T1-T3-R1-T4-T6 with a washout period of at least 4 days between treatments. All test treatments (T1-T6) were one single dose of 62.5 milligram. R1 and T1-T4: taken orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. T5-T6: taken orally with 240 mL of water following a high-fat high-calorie breakfast.
Reference (R1): 60 milligram (mg) (6 x 10 mg tablets) BI 894416 Reference Formulation, immediate release (IR) tablets.
Test 1 (T1): 1 tablet BI 894416 Formulation A2, extended release (ER) tablet (fast release rate, FRR).
Test 2 (T2): 1 tablet BI 894416 Formulation C2, ER tablet (slow release rate, SRR).
Test 3 (T3): 1 capsule BI 894416 Formulation D2, ER capsule (FRR). Test 4 (T4): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). Test 5 (T5): 1 tablet BI 894416 Formulation C2, ER tablet (SRR). Test 6 (T6): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). | 3 |
| T4-T3-R1-T2-T1-T5 (Sequence III+T5) Sequence III+T5, with treatments in the following order: T4-T3-R1-T2-T1-T5 with a washout period of at least 4 days between treatments. All test treatments (T1-T6) were one single dose of 62.5 milligram. R1 and T1-T4: taken orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. T5-T6: taken orally with 240 mL of water following a high-fat high-calorie breakfast.
Reference (R1): 60 milligram (mg) (6 x 10 mg tablets) BI 894416 Reference Formulation, immediate release (IR) tablets.
Test 1 (T1): 1 tablet BI 894416 Formulation A2, extended release (ER) tablet (fast release rate, FRR).
Test 2 (T2): 1 tablet BI 894416 Formulation C2, ER tablet (slow release rate, SRR).
Test 3 (T3): 1 capsule BI 894416 Formulation D2, ER capsule (FRR). Test 4 (T4): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). Test 5 (T5): 1 tablet BI 894416 Formulation C2, ER tablet (SRR). Test 6 (T6): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). | 2 |
| T4-T3-R1-T2-T1-T6 (Sequence III+T6) Sequence III+T6, with treatments in the following order: T4-T3-R1-T2-T1-T6 with a washout period of at least 4 days between treatments. All test treatments (T1-T6) were one single dose of 62.5 milligram. R1 and T1-T4: taken orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. T5-T6: taken orally with 240 mL of water following a high-fat high-calorie breakfast.
Reference (R1): 60 milligram (mg) (6 x 10 mg tablets) BI 894416 Reference Formulation, immediate release (IR) tablets.
Test 1 (T1): 1 tablet BI 894416 Formulation A2, extended release (ER) tablet (fast release rate, FRR).
Test 2 (T2): 1 tablet BI 894416 Formulation C2, ER tablet (slow release rate, SRR).
Test 3 (T3): 1 capsule BI 894416 Formulation D2, ER capsule (FRR). Test 4 (T4): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). Test 5 (T5): 1 tablet BI 894416 Formulation C2, ER tablet (SRR). Test 6 (T6): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). | 2 |
| T1-T4-T2-T3-R1-T5 (Sequence IV+T5) Sequence IV+T5, with treatments in the following order: T1-T4-T2-T3-R1-T5 with a washout period of at least 4 days between treatments. All test treatments (T1-T6) were one single dose of 62.5 milligram. R1 and T1-T4: taken orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. T5-T6: taken orally with 240 mL of water following a high-fat high-calorie breakfast.
Reference (R1): 60 milligram (mg) (6 x 10 mg tablets) BI 894416 Reference Formulation, immediate release (IR) tablets.
Test 1 (T1): 1 tablet BI 894416 Formulation A2, extended release (ER) tablet (fast release rate, FRR).
Test 2 (T2): 1 tablet BI 894416 Formulation C2, ER tablet (slow release rate, SRR).
Test 3 (T3): 1 capsule BI 894416 Formulation D2, ER capsule (FRR). Test 4 (T4): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). Test 5 (T5): 1 tablet BI 894416 Formulation C2, ER tablet (SRR). Test 6 (T6): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). | 3 |
| T1-T4-T2-T3-R1-T6 (Sequence IV+T6) Sequence IV+T6, with treatments in the following order: T1-T4-T2-T3-R1-T6 with a washout period of at least 4 days between treatments. All test treatments (T1-T6) were one single dose of 62.5 milligram. R1 and T1-T4: taken orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. T5-T6: taken orally with 240 mL of water following a high-fat high-calorie breakfast.
Reference (R1): 60 milligram (mg) (6 x 10 mg tablets) BI 894416 Reference Formulation, immediate release (IR) tablets.
Test 1 (T1): 1 tablet BI 894416 Formulation A2, extended release (ER) tablet (fast release rate, FRR).
Test 2 (T2): 1 tablet BI 894416 Formulation C2, ER tablet (slow release rate, SRR).
Test 3 (T3): 1 capsule BI 894416 Formulation D2, ER capsule (FRR). Test 4 (T4): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). Test 5 (T5): 1 tablet BI 894416 Formulation C2, ER tablet (SRR). Test 6 (T6): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). | 3 |
| R1-T2-T4-T1-T3-T5 (Sequence V+T5) Sequence V+T5, with treatments in the following order: R1-T2-T4-T1-T3-T5 with a washout period of at least 4 days between treatments. All test treatments (T1-T6) were one single dose of 62.5 milligram. R1 and T1-T4: taken orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. T5-T6: taken orally with 240 mL of water following a high-fat high-calorie breakfast.
Reference (R1): 60 milligram (mg) (6 x 10 mg tablets) BI 894416 Reference Formulation, immediate release (IR) tablets.
Test 1 (T1): 1 tablet BI 894416 Formulation A2, extended release (ER) tablet (fast release rate, FRR).
Test 2 (T2): 1 tablet BI 894416 Formulation C2, ER tablet (slow release rate, SRR).
Test 3 (T3): 1 capsule BI 894416 Formulation D2, ER capsule (FRR). Test 4 (T4): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). Test 5 (T5): 1 tablet BI 894416 Formulation C2, ER tablet (SRR). Test 6 (T6): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). | 2 |
| R1-T2-T4-T1-T3-T6 (Sequence V+T6) Sequence V+T6, with treatments in the following order: R1-T2-T4-T1-T3-T6with a washout period of at least 4 days between treatments. All test treatments (T1-T6) were one single dose of 62.5 milligram. R1 and T1-T4: taken orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. T5-T6: taken orally with 240 mL of water following a high-fat high-calorie breakfast.
Reference (R1): 60 milligram (mg) (6 x 10 mg tablets) BI 894416 Reference Formulation, immediate release (IR) tablets.
Test 1 (T1): 1 tablet BI 894416 Formulation A2, extended release (ER) tablet (fast release rate, FRR).
Test 2 (T2): 1 tablet BI 894416 Formulation C2, ER tablet (slow release rate, SRR).
Test 3 (T3): 1 capsule BI 894416 Formulation D2, ER capsule (FRR). Test 4 (T4): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). Test 5 (T5): 1 tablet BI 894416 Formulation C2, ER tablet (SRR). Test 6 (T6): 1 capsule BI 894416 Formulation F2, ER capsule (SRR). | 3 |
| Total | 24 |
Baseline characteristics
| Characteristic | T3-R1-T1-T4-T2-T5 (Sequence I+T5) | T3-R1-T1-T4-T2-T6 (Sequence I+T6) | T2-T1-T3-R1-T4-T5 (Sequence II+T5) | T2-T1-T3-R1-T4-T6 (Sequence II+T6) | T4-T3-R1-T2-T1-T5 (Sequence III+T5) | T4-T3-R1-T2-T1-T6 (Sequence III+T6) | T1-T4-T2-T3-R1-T5 (Sequence IV+T5) | T1-T4-T2-T3-R1-T6 (Sequence IV+T6) | R1-T2-T4-T1-T3-T5 (Sequence V+T5) | R1-T2-T4-T1-T3-T6 (Sequence V+T6) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 35.5 years STANDARD_DEVIATION 17.7 | 37.0 years STANDARD_DEVIATION 0 | 29.5 years STANDARD_DEVIATION 7.8 | 30.3 years STANDARD_DEVIATION 4 | 39.0 years STANDARD_DEVIATION 8.5 | 31.5 years STANDARD_DEVIATION 2.1 | 30.0 years STANDARD_DEVIATION 8.2 | 43.3 years STANDARD_DEVIATION 13.2 | 25.0 years STANDARD_DEVIATION 4.2 | 25.3 years STANDARD_DEVIATION 5.9 | 32.6 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 22 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 11 | 0 / 13 |
| other Total, other adverse events | 1 / 24 | 1 / 24 | 3 / 24 | 2 / 24 | 2 / 24 | 3 / 11 | 2 / 13 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 11 | 0 / 13 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
Time frame: Within 3 hours before and 0.33, 0.66, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24, 34, 48, 58 and 72 hours following drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This analysis set included all subjects who were randomised, received at least one dose of trial medication and who provided at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference 1 - BI 894416 Reference Formulation Tablet, Fasted | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 9800 hour*nanomol/Liter | Geometric Coefficient of Variation 30.6 |
| Test 1 - BI 894416 Fast Release Rate (FRR) Tablet, Fasted | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 8260 hour*nanomol/Liter | Geometric Coefficient of Variation 29.6 |
| Test 2 - BI 894416 Slow Release Rate (SRR) Tablet, Fasted | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 7030 hour*nanomol/Liter | Geometric Coefficient of Variation 31.7 |
| Test 3 - BI 894416 Fast Release Rate (FRR) Capsule, Fasted | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 9100 hour*nanomol/Liter | Geometric Coefficient of Variation 33.3 |
| Test 4 - BI 894416 Slow Release Rate (SRR) Capsule, Fasted | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 7430 hour*nanomol/Liter | Geometric Coefficient of Variation 35.8 |
| Test 5 - BI 894416 Slow Release Rate (SRR) Tablet, Fed | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 9680 hour*nanomol/Liter | Geometric Coefficient of Variation 31.1 |
| Test 6 - BI 894416 Slow Release Rate (SRR) Capsule, Fed | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 8930 hour*nanomol/Liter | Geometric Coefficient of Variation 24.8 |
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale, including effects accounting for 'sequence', 'subjects nested within sequences', 'period', and 'treatment' (formulation). The effect 'subjects within sequences' was to be considered as random, while the other effects were to be considered as fixed.90% CI: [80.3, 91.7]
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale, including effects accounting for 'sequence', 'subjects nested within sequences', 'period', and 'treatment' (formulation). The effect 'subjects within sequences' was to be considered as random, while the other effects were to be considered as fixed.90% CI: [68, 77.6]
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale, including effects accounting for 'sequence', 'subjects nested within sequences', 'period', and 'treatment' (formulation). The effect 'subjects within sequences' was to be considered as random, while the other effects were to be considered as fixed.90% CI: [86.5, 98.8]
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale, including effects accounting for 'sequence', 'subjects nested within sequences', 'period', and 'treatment' (formulation). The effect 'subjects within sequences' was to be considered as random, while the other effects were to be considered as fixed.90% CI: [71.6, 81.8]
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale, including effects accounting for 'subjects' and 'treatment'. The effect 'subjects' were to be considered as random, while the effect 'treatment' was to be considered as fixed.90% CI: [117.2, 151.9]
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale, including effects accounting for 'subjects' and 'treatment'. The effect 'subjects' were to be considered as random, while the effect 'treatment' was to be considered as fixed.90% CI: [102.3, 127.6]
Secondary
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
Time frame: Within 3 hours before and 0.33, 0.66, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24, 34, 48, 58 and 72 hours following drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This analysis set included all subjects who were randomised, received at least one dose of trial medication and who provided at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference 1 - BI 894416 Reference Formulation Tablet, Fasted | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 9780 hour*nanomol/Liter | Geometric Coefficient of Variation 30.5 |
| Test 1 - BI 894416 Fast Release Rate (FRR) Tablet, Fasted | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 8200 hour*nanomol/Liter | Geometric Coefficient of Variation 29.5 |
| Test 2 - BI 894416 Slow Release Rate (SRR) Tablet, Fasted | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 6950 hour*nanomol/Liter | Geometric Coefficient of Variation 31.8 |
| Test 3 - BI 894416 Fast Release Rate (FRR) Capsule, Fasted | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 9050 hour*nanomol/Liter | Geometric Coefficient of Variation 33.2 |
| Test 4 - BI 894416 Slow Release Rate (SRR) Capsule, Fasted | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 7310 hour*nanomol/Liter | Geometric Coefficient of Variation 36.3 |
| Test 5 - BI 894416 Slow Release Rate (SRR) Tablet, Fed | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 9600 hour*nanomol/Liter | Geometric Coefficient of Variation 30.6 |
| Test 6 - BI 894416 Slow Release Rate (SRR) Capsule, Fed | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 8850 hour*nanomol/Liter | Geometric Coefficient of Variation 24.9 |
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale, including effects accounting for 'sequence', 'subjects nested within sequences', 'period', and 'treatment' (formulation). The effect 'subjects within sequences' was to be considered as random, while the other effects were to be considered as fixed.90% CI: [80, 91.4]
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale, including effects accounting for 'sequence', 'subjects nested within sequences', 'period', and 'treatment' (formulation). The effect 'subjects within sequences' was to be considered as random, while the other effects were to be considered as fixed.90% CI: [67.4, 77.1]
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale, including effects accounting for 'sequence', 'subjects nested within sequences', 'period', and 'treatment' (formulation). The effect 'subjects within sequences' was to be considered as random, while the other effects were to be considered as fixed.90% CI: [86.3, 98.6]
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale, including effects accounting for 'sequence', 'subjects nested within sequences', 'period', and 'treatment' (formulation). The effect 'subjects within sequences' was to be considered as random, while the other effects were to be considered as fixed.90% CI: [70.6, 80.7]
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale, including effects accounting for 'subjects' and 'treatment'. The effect 'subjects' were to be considered as random, while the effect 'treatment' was to be considered as fixed.90% CI: [117.6, 153]
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale, including effects accounting for 'subjects' and 'treatment'. The effect 'subjects' were to be considered as random, while the effect 'treatment' was to be considered as fixed.90% CI: [102.9, 128.1]