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
Condition: Osteoarthritis
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Intervention: BI 1026706; Placebo to BI 1026706
Intervention description: Multiple Rising Doses (oral solution, tablet); Multiple Rising Doses (oral solution / tablet, identical to active treatment)
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 58.0
Sex: All
Minimum age: 35 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      -  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
    

Eligibility criteria:

        Inclusion criteria:

          1. 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

          2. 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

          3. For OA patients: American Rheumatism Association (ARA) functional class I, II, or III

          4. 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

          5. 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.

          6. Age 35 to 65 years (inclusive)

          7. BMI (Body Mass Index) 18.5 to 33 kg/m2 (inclusive)

          8. Signed and dated written informed consent prior to admission to the study in
             accordance with GCP and local legislation

          9. 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:

          1. Any finding in the medical examination (including Blood Pressure, Pulse Rate or
             electrocardiogram) deviating from normal and judged clinically relevant by the
             investigator

          2. Repeated measurement of systolic blood pressure greater than 140 mm Hg or diastolic
             blood pressure greater than 90 mm Hg

          3. Any laboratory value outside the reference range that the investigator considers to be
             of clinical relevance

          4. Any evidence of a concomitant disease judged clinically relevant by the investigator

          5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,
             immunological or hormonal disorders

          6. Surgery of the gastrointestinal tract that could interfere with kinetics of the study
             drug(s)

          7. Diseases of the central nervous system (such as epilepsy), other neurological
             disorders or psychiatric disorders