Trial Outcomes & Findings for 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 (NCT NCT02126826)

NCT ID: NCT02126826

Last Updated: 2019-03-25

Results Overview

Percentage of subjects with drug related adverse events (AEs)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

58 participants

Primary outcome timeframe

From first drug administration until 3 days after last drug administration, 15 days

Results posted on

2019-03-25

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo HV Healthy volunteers (HV) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	50mg BI 1026706 HV Healthy volunteers (HV) received 50mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 HV Healthy volunteers (HV) received 100mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	300mg BI 1026706 HV Healthy volunteers (HV) received 300mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	Placebo OA Patients with osteoarthritis (OA) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	200mg BI 1026706 OA Patients with osteoarthritis received 200mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 BID OA Patients with osteoarthritis received oral administration of 100mg BI 1026706 tablets twice daily (BID) on days 2 to 11 and once daily on days 1 and 12.
Overall Study STARTED	9	9	9	9	5	9	8
Overall Study COMPLETED	9	9	9	8	5	9	8
Overall Study NOT COMPLETED	0	0	0	1	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo HV Healthy volunteers (HV) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	50mg BI 1026706 HV Healthy volunteers (HV) received 50mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 HV Healthy volunteers (HV) received 100mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	300mg BI 1026706 HV Healthy volunteers (HV) received 300mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	Placebo OA Patients with osteoarthritis (OA) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	200mg BI 1026706 OA Patients with osteoarthritis received 200mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 BID OA Patients with osteoarthritis received oral administration of 100mg BI 1026706 tablets twice daily (BID) on days 2 to 11 and once daily on days 1 and 12.
Overall Study Withdrawal by Subject	0	0	0	1	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo HV n=9 Participants Healthy volunteers (HV) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	50mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 50mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 100mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	300mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 300mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	Placebo OA n=5 Participants Patients with osteoarthritis (OA) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	200mg BI 1026706 OA n=9 Participants Patients with osteoarthritis received 200mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 BID OA n=8 Participants Patients with osteoarthritis received oral administration of 100mg BI 1026706 tablets twice daily (BID) on days 2 to 11 and once daily on days 1 and 12.	Total n=58 Participants Total of all reporting groups
Age, Continuous	48.3 Years STANDARD_DEVIATION 9.6 • n=5 Participants	43.6 Years STANDARD_DEVIATION 5.3 • n=7 Participants	50.1 Years STANDARD_DEVIATION 11.8 • n=5 Participants	48.7 Years STANDARD_DEVIATION 8.8 • n=4 Participants	50.2 Years STANDARD_DEVIATION 10.8 • n=21 Participants	49.8 Years STANDARD_DEVIATION 8.4 • n=10 Participants	58.1 Years STANDARD_DEVIATION 4.9 • n=115 Participants	49.7 Years STANDARD_DEVIATION 9.2 • n=24 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	3 Participants n=21 Participants	2 Participants n=10 Participants	5 Participants n=115 Participants	28 Participants n=24 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	2 Participants n=21 Participants	7 Participants n=10 Participants	3 Participants n=115 Participants	30 Participants n=24 Participants

PRIMARY outcome

Timeframe: From first drug administration until 3 days after last drug administration, 15 days

Population: Treated set (TS)

Percentage of subjects with drug related adverse events (AEs)

Outcome measures

Outcome measures
Measure	Placebo HV n=9 Participants Healthy volunteers (HV) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	50mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 50mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 100mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	300mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 300mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	Placebo OA n=5 Participants Patients with osteoarthritis (OA) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	200mg BI 1026706 OA n=9 Participants Patients with osteoarthritis received 200mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 BID OA n=8 Participants Patients with osteoarthritis received oral administration of 100mg BI 1026706 tablets twice daily (BID) on days 2 to 11 and once daily on days 1 and 12.
Percentage of Subjects With Drug Related Adverse Events	22.2 Percentage of participants	22.2 Percentage of participants	11.1 Percentage of participants	66.7 Percentage of participants	60.0 Percentage of participants	55.6 Percentage of participants	37.5 Percentage of participants

SECONDARY outcome

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

Population: Pharmacokinetic set (PKS) which included all patients and healthy subjects in the TS who provided at least 1 PK endpoint value without relevant protocol deviations with respect to the evaluation of PK endpoints.

Maximum measured concentration of the analyte in plasma (Cmax)

Outcome measures

Outcome measures
Measure	Placebo HV n=9 Participants Healthy volunteers (HV) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	50mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 50mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 HV n=8 Participants Healthy volunteers (HV) received 100mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	300mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 300mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	Placebo OA n=8 Participants Patients with osteoarthritis (OA) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	200mg BI 1026706 OA Patients with osteoarthritis received 200mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 BID OA Patients with osteoarthritis received oral administration of 100mg BI 1026706 tablets twice daily (BID) on days 2 to 11 and once daily on days 1 and 12.
Maximum Measured Concentration (Cmax)	423 nmol/L Geometric Coefficient of Variation 31.2	1010 nmol/L Geometric Coefficient of Variation 25.3	1600 nmol/L Geometric Coefficient of Variation 54.3	1730 nmol/L Geometric Coefficient of Variation 36.1	578 nmol/L Geometric Coefficient of Variation 53.6	—	—

SECONDARY outcome

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.

Population: PKS

Time from dosing to maximum measured concentration of the analyte in plasma (Tmax)

Outcome measures

Outcome measures
Measure	Placebo HV n=9 Participants Healthy volunteers (HV) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	50mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 50mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 HV n=8 Participants Healthy volunteers (HV) received 100mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	300mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 300mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	Placebo OA n=8 Participants Patients with osteoarthritis (OA) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	200mg BI 1026706 OA Patients with osteoarthritis received 200mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 BID OA Patients with osteoarthritis received oral administration of 100mg BI 1026706 tablets twice daily (BID) on days 2 to 11 and once daily on days 1 and 12.
Time From Dosing to Maximum Measured Concentration (Tmax)	0.52 hours Interval 0.47 to 2.0	0.52 hours Interval 0.33 to 0.98	0.69 hours Interval 0.37 to 2.53	0.75 hours Interval 0.5 to 1.08	1.53 hours Interval 0.75 to 8.13	—	—

SECONDARY outcome

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

Population: PKS

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 24 hours (h) (AUC0-24).

Outcome measures

Outcome measures
Measure	Placebo HV n=9 Participants Healthy volunteers (HV) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	50mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 50mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 HV n=8 Participants Healthy volunteers (HV) received 100mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	300mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 300mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	Placebo OA n=8 Participants Patients with osteoarthritis (OA) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	200mg BI 1026706 OA Patients with osteoarthritis received 200mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 BID OA Patients with osteoarthritis received oral administration of 100mg BI 1026706 tablets twice daily (BID) on days 2 to 11 and once daily on days 1 and 12.
Area Under the Concentration-time Curve Over the Time Interval From 0 Extrapolated to 24h (AUC0-24)	1230 nmol*h/L Geometric Coefficient of Variation 44.9	2790 nmol*h/L Geometric Coefficient of Variation 26.7	6410 nmol*h/L Geometric Coefficient of Variation 66.2	5530 nmol*h/L Geometric Coefficient of Variation 44.9	2790 nmol*h/L Geometric Coefficient of Variation 58.5	—	—

SECONDARY outcome

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

Population: PKS

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 12 hours (h) (AUC0-12).

Outcome measures

Outcome measures
Measure	Placebo HV n=9 Participants Healthy volunteers (HV) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	50mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 50mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 HV n=8 Participants Healthy volunteers (HV) received 100mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	300mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 300mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	Placebo OA n=8 Participants Patients with osteoarthritis (OA) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	200mg BI 1026706 OA Patients with osteoarthritis received 200mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 BID OA Patients with osteoarthritis received oral administration of 100mg BI 1026706 tablets twice daily (BID) on days 2 to 11 and once daily on days 1 and 12.
Area Under the Concentration-time Curve Over the Time Interval From 0 Extrapolated to 12h (AUC0-12)	1050 nmol*h/L Geometric Coefficient of Variation 41.3	2370 nmol*h/L Geometric Coefficient of Variation 27.8	5080 nmol*h/L Geometric Coefficient of Variation 63.6	4720 nmol*h/L Geometric Coefficient of Variation 45.1	2290 nmol*h/L Geometric Coefficient of Variation 54.2	—	—

SECONDARY outcome

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

Population: PKS

Maximum measured concentration of the analyte in plasma at steady-state over a uniform dosing interval τ (Cmax,ss).

Outcome measures

Outcome measures
Measure	Placebo HV n=9 Participants Healthy volunteers (HV) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	50mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 50mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 HV n=8 Participants Healthy volunteers (HV) received 100mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	300mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 300mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	Placebo OA n=8 Participants Patients with osteoarthritis (OA) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	200mg BI 1026706 OA Patients with osteoarthritis received 200mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 BID OA Patients with osteoarthritis received oral administration of 100mg BI 1026706 tablets twice daily (BID) on days 2 to 11 and once daily on days 1 and 12.
Maximum Measured Concentration at Steady-state (Cmax,ss)	485 nmol/L Geometric Coefficient of Variation 37.4	1190 nmol/L Geometric Coefficient of Variation 26.1	1800 nmol/L Geometric Coefficient of Variation 43.3	2040 nmol/L Geometric Coefficient of Variation 27.0	723 nmol/L Geometric Coefficient of Variation 65.1	—	—

SECONDARY outcome

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

Population: PKS

Time from last dosing to maximum concentration of the analyte in plasma at steady-state (Tmax,ss).

Outcome measures

Outcome measures
Measure	Placebo HV n=9 Participants Healthy volunteers (HV) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	50mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 50mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 HV n=8 Participants Healthy volunteers (HV) received 100mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	300mg BI 1026706 HV n=9 Participants Healthy volunteers (HV) received 300mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	Placebo OA n=8 Participants Patients with osteoarthritis (OA) received a matching placebo containing quinine sulphate dehydrate, once daily for 12 days.	200mg BI 1026706 OA Patients with osteoarthritis received 200mg BI 1026706 once daily on days 1 to 12 in the form of a powder for oral solution.	100mg BI 1026706 BID OA Patients with osteoarthritis received oral administration of 100mg BI 1026706 tablets twice daily (BID) on days 2 to 11 and once daily on days 1 and 12.
Time From Last Dosing to Maximum Measured Concentration at Steady-state (Tmax,ss)	0.53 hours Interval 0.3 to 1.0	0.52 hours Interval 0.35 to 1.02	0.58 hours Interval 0.45 to 1.02	0.58 hours Interval 0.33 to 1.05	1.13 hours Interval 0.73 to 3.03	—	—

SECONDARY outcome

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

Population: PKS

Area under the concentration-time curve of the analyte in plasma at steady-state over a uniform dosing interval τ (AUCτ,ss).