Clinical trial NCT02126826: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteoarthritis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-04-30
Enrollment: 58
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Percentage of Subjects With Drug Related Adverse Events
timeFrame: From first drug administration until 3 days after last drug administration, 15 days
Secondary outcomes:
measure: Maximum Measured Concentration (Cmax)
timeFrame: 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
measure: Time From Dosing to Maximum Measured Concentration (Tmax)
timeFrame: 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.
measure: Area Under the Concentration-time Curve Over the Time Interval From 0 Extrapolated to 24h (AUC0-24)
timeFrame: 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
measure: Area Under the Concentration-time Curve Over the Time Interval From 0 Extrapolated to 12h (AUC0-12)
timeFrame: 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
measure: Maximum Measured Concentration at Steady-state (Cmax,ss)
timeFrame: 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
measure: Time From Last Dosing to Maximum Measured Concentration at Steady-state (Tmax,ss)
timeFrame: 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
measure: Area Under the Concentration-time Curve at Steady-state (AUCτ,ss)
timeFrame: 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
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: 1320.2.2 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: