Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 1026706 in Male and Female Healthy Subjects and Patients With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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To investigate the safety and tolerability of BI 1026706 in male and female healthy subjects and osteoarthritis (OA) patients following oral administration of repeated rising doses To explore the pharmacokinetics after multiple rising doses of BI 1026706 in male and female healthy subjects and OA patients The assessment of pharmacodynamics in OA patients

Official Title
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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 1026706 in Male and Female Healthy Subjects and Patients With Osteoarthritis of the Knee (Randomised, Double-blind, Placebo-controlled Within the Dose Groups, Clinical Phase I)

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: BI 1026706
* Drug: Placebo to BI 1026706


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Males or females without any clinically relevant medical disorders according to the investigator's assessment, as based on the following: a complete medical history including a physical examination, vital signs (blood pressure, pulse rate), 12-lead electrocardiogram, and clinical laboratory tests For OA patients: Evidence of OA of the knee by radiography or by magnetic resonance tomography (Kellgren-Lawrence grade 1, 2, or 3; excluding grades 0 and 4) of the knee (tibiofemoral joint only) within the last 5 years consistent with the clinical diagnosis of osteoarthritis of the knee according to American College of Rheumatology (ACR) guidelines For OA patients: American Rheumatism Association (ARA) functional class I, II, or III For OA patients: Average pain in the index knee over the previous 48 hours greater than or equal to 4 on the 11-item Likert scale at two time points: 1) at screening (if not on analgesic medication) or after 3 days of wash-out of analgesic medication, and 2) in the evening prior to randomisation For OA patients: Presence of bothersome OA related pain for most days within the last month prior to screening at the investigator's discretion, or pain requiring analgesic treatment on more than 3 days per week during the last month prior to screening. Age 35 to 65 years (inclusive) BMI (Body Mass Index) 18.5 to 33 kg/m2 (inclusive) Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation Females who meet any of the following criteria from at least 30 days before the first study drug administration and until 30 days after trial completion: using adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral contraceptives, intrauterine device (IUD) sexually abstinent have 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 simultaneous levels of FSH (Follicle Stimulating Hormon) above 40 U/L and estradiol below 30 ng/L is confirmatory) Exclusion criteria: Any finding in the medical examination (including Blood Pressure, Pulse Rate or electrocardiogram) deviating from normal and judged clinically relevant by the investigator Repeated measurement of systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg Any laboratory value outside the reference range that the investigator considers to be of clinical relevance Any evidence of a concomitant disease judged clinically relevant by the investigator Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of the gastrointestinal tract that could interfere with kinetics of the study drug(s) Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo to BI 1026706<br>Multiple Rising Doses Placebo to BI 1026706 | Drug: Placebo to BI 1026706<br>* Multiple Rising Doses (oral solution / tablet, identical to active treatment)<br>|
| Experimental: BI 1026706<br>Multiple Rising Doses BI 1026706 | Drug: BI 1026706<br>* Multiple Rising Doses (oral solution, tablet)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Drug Related Adverse Events | Percentage of subjects with drug related adverse events (AEs) | From first drug administration until 3 days after last drug administration, 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Measured Concentration (Cmax) | Maximum measured concentration of the analyte in plasma (Cmax) | 1 hour (h) 30 minutes (min) before first drug admin and 10min, 20min, 30min, 45min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 14h and 23h 55min after first drug admin | 
| Time From Dosing to Maximum Measured Concentration (Tmax) | Time from dosing to maximum measured concentration of the analyte in plasma (Tmax) | 1 hour (h) 30 minutes (min) before first drug admin and 10min, 20min, 30min, 45min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 14h and 23h 55min after first drug admin. | 
| Area Under the Concentration-time Curve Over the Time Interval From 0 Extrapolated to 24h (AUC0-24) | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 24 hours (h) (AUC0-24). | 1 hour (h) 30 minutes (min) before first drug admin and 10min, 20min, 30min, 45min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 14h and 23h 55min after first drug admin | 
| Area Under the Concentration-time Curve Over the Time Interval From 0 Extrapolated to 12h (AUC0-12) | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 12 hours (h) (AUC0-12). | 1 hour (h) 30 minutes (min) before first drug admin and 10min, 20min, 30min, 45min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h and 12h after first drug admin | 
| Maximum Measured Concentration at Steady-state (Cmax,ss) | Maximum measured concentration of the analyte in plasma at steady-state over a uniform dosing interval τ (Cmax,ss). | 5 minutes (min) before drug admin on day 12 and 10min, 20min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 14h and 24h after drug admin on day 12 | 
| Time From Last Dosing to Maximum Measured Concentration at Steady-state (Tmax,ss) | Time from last dosing to maximum concentration of the analyte in plasma at steady-state (Tmax,ss). | 5 minutes (min) before drug admin on day 12 and 10min, 20min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 14h and 24h after drug admin on day 12 | 
| Area Under the Concentration-time Curve at Steady-state (AUCτ,ss) | Area under the concentration-time curve of the analyte in plasma at steady-state over a uniform dosing interval τ (AUCτ,ss). | 5 minutes (min) before drug admin on day 12 and 10min, 20min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 14h and 24h after drug admin on day 12 |