Trial Outcomes & Findings for Study to Investigate the Pharmacokinetics (PK) and Pharmacodynamics (PD) of Idarucizumab in Chinese Healthy Male and Female Volunteers Who Had Taken Dabigatran Etexilate and Whose Plasma Concentrations of Dabigatran Were at or Close to Steady State (NCT NCT03086356)
NCT ID: NCT03086356
Last Updated: 2019-03-08
Results Overview
Cmax, maximum measured concentration of idarucizumab in plasma
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
12 participants
Primary outcome timeframe
-0.017, 0.083, 0.167, 0.317, 0.417, 0.45, 0.583, 0.917, 1.417, 2.083, 3.083, 4.083, 6.083, 10.083, 12.083, 24.083, 48.083, 72.083 hours (h)
Results posted on
2019-03-08
Participant Flow
This was a single-centre, open-label trial in 1 group of healthy volunteers. The trial included a 2-week treatment period during which the subjects were hospitalised at the trial site and a follow-up period of approximately 3 months.
Healthy male and female volunteers, aged ≥18 and ≤45 years, body weight ≥50 kilograms (kg) with a Body Mass Index (BMI) in the range from ≥19 to \<24 kilogram per square meter (kg/m2) were included in the trial.
Participant milestones
| Measure |
Dabigatran Etexilate+Idarucizumab
During the first part of the treatment period, dabigatran etexilate was administered alone. All subjects received 220 milligram (mg) dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 1 to 3) and a single 220 mg dose on Day 4. During the second part of the treatment period, after a washout period of 3 days, subjects again received dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 8 to 10) and a single 220 mg dose on Day 11. Idarucizumab (solution for infusion) 2 short infusions of 2.5 grams (g) each, with a 15 minute (min) interval was administered intravenously approximately 2 hours (h) after the last dabigatran etexilate administration.
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
TS
Baseline characteristics by cohort
| Measure |
Dabigatran Etexilate+Idarucizumab
n=12 Participants
During the first part of the treatment period, dabigatran etexilate was administered alone. All subjects received 220 milligram (mg) dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 1 to 3) and a single 220 mg dose on Day 4. During the second part of the treatment period, after a washout period of 3 days, subjects again received dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 8 to 10) and a single 220 mg dose on Day 11. Idarucizumab (solution for infusion) 2 short infusions of 2.5 grams (g) each, with a 15 minute (min) interval was administered intravenously approximately 2 hours (h) after the last dabigatran etexilate administration.
|
|---|---|
|
Age, Continuous
|
35.6 years
STANDARD_DEVIATION 5.8 • n=5 Participants • TS
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants • TS
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
Asian
|
12 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants • TS
|
PRIMARY outcome
Timeframe: -0.017, 0.083, 0.167, 0.317, 0.417, 0.45, 0.583, 0.917, 1.417, 2.083, 3.083, 4.083, 6.083, 10.083, 12.083, 24.083, 48.083, 72.083 hours (h)Population: Pharmacokinetic set (PKS): The PKS included all subjects of the Treated set (TS) who had at least one Pharmacokinetic (PK) parameter analysed.
Cmax, maximum measured concentration of idarucizumab in plasma
Outcome measures
| Measure |
Dabigatran Etexilate+Idarucizumab
n=12 Participants
During the first part of the treatment period, dabigatran etexilate was administered alone. All subjects received 220 milligram (mg) dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 1 to 3) and a single 220 mg dose on Day 4. During the second part of the treatment period, after a washout period of 3 days, subjects again received dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 8 to 10) and a single 220 mg dose on Day 11. Idarucizumab (solution for infusion) 2 short infusions of 2.5 grams (g) each, with a 15 minute (min) interval was administered intravenously approximately 2 hours (h) after the last dabigatran etexilate administration.
|
|---|---|
|
Maximum Measured Concentration of Idarucizumab in Plasma (Cmax)
|
30900 nanomoles (nmol) per litre (L)
Geometric Coefficient of Variation 9.86
|
PRIMARY outcome
Timeframe: Day 4 and day 11Population: Pharmacodynamic set (PDS): The PDS included all subjects in the TS who provided at least one evaluable pre-dose and one on-treatment PD observation after the start of dabigatran administration.
For diluted thrombin time: AUEC above,2-12 (area after subtraction of baseline area from area under the effect curve over the time interval from 2 - 12) on day 4 and day 11. The standard deviation (SD) presented is actually the percentage coefficient of variation (CV %)
Outcome measures
| Measure |
Dabigatran Etexilate+Idarucizumab
n=12 Participants
During the first part of the treatment period, dabigatran etexilate was administered alone. All subjects received 220 milligram (mg) dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 1 to 3) and a single 220 mg dose on Day 4. During the second part of the treatment period, after a washout period of 3 days, subjects again received dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 8 to 10) and a single 220 mg dose on Day 11. Idarucizumab (solution for infusion) 2 short infusions of 2.5 grams (g) each, with a 15 minute (min) interval was administered intravenously approximately 2 hours (h) after the last dabigatran etexilate administration.
|
|---|---|
|
For Diluted Thrombin Time: Area After Subtraction of Baseline Area From Area Under the Effect Curve Over the Time Interval From 2 - 12 Hours (AUEC Above,2-12) on Day 4 and Day 11
Day 4
|
8.23 hours
Standard Deviation 32.0
|
|
For Diluted Thrombin Time: Area After Subtraction of Baseline Area From Area Under the Effect Curve Over the Time Interval From 2 - 12 Hours (AUEC Above,2-12) on Day 4 and Day 11
Day 11
|
0.118 hours
Standard Deviation 140
|
PRIMARY outcome
Timeframe: -0.017, 0.083, 0.167, 0.317, 0.417, 0.45, 0.583, 0.917, 1.417, 2.083, 3.083, 4.083, 6.083, 10.083, 12.083, 24.083, 48.083, 72.083 hours (h)Population: PKS
AUC0-∞, area under the concentration-time curve of idarucizumab in plasma over the time interval from 0 extrapolated to infinity
Outcome measures
| Measure |
Dabigatran Etexilate+Idarucizumab
n=12 Participants
During the first part of the treatment period, dabigatran etexilate was administered alone. All subjects received 220 milligram (mg) dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 1 to 3) and a single 220 mg dose on Day 4. During the second part of the treatment period, after a washout period of 3 days, subjects again received dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 8 to 10) and a single 220 mg dose on Day 11. Idarucizumab (solution for infusion) 2 short infusions of 2.5 grams (g) each, with a 15 minute (min) interval was administered intravenously approximately 2 hours (h) after the last dabigatran etexilate administration.
|
|---|---|
|
Area Under the Concentration-time Curve of Idarucizumab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
|
44200 nanomoles (nmol)*hours (h) per litre (L)
Geometric Coefficient of Variation 10.1
|
PRIMARY outcome
Timeframe: 0-2 h, 2-6 h, 6-10 h, 10-12 h,12-14h, 14-26 h, 26-50 h, 50-74 h after drug administration of dabigatran etexilate on Day 4Population: PKS
Ae0-72, amount of idarucizumab eliminated in urine over the time interval from 0 to 72 h. As per the protocol, day is counted as "Day 1 = 0:00"
Outcome measures
| Measure |
Dabigatran Etexilate+Idarucizumab
n=12 Participants
During the first part of the treatment period, dabigatran etexilate was administered alone. All subjects received 220 milligram (mg) dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 1 to 3) and a single 220 mg dose on Day 4. During the second part of the treatment period, after a washout period of 3 days, subjects again received dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 8 to 10) and a single 220 mg dose on Day 11. Idarucizumab (solution for infusion) 2 short infusions of 2.5 grams (g) each, with a 15 minute (min) interval was administered intravenously approximately 2 hours (h) after the last dabigatran etexilate administration.
|
|---|---|
|
Amount of Idarucizumab Eliminated in Urine Over the Time Interval From 0 to 72 Hours (h) (Ae0-72)
|
35.3 micromole (μmol)
Geometric Coefficient of Variation 57.1
|
SECONDARY outcome
Timeframe: 0-2 h, 2-6 h, 6-10 h, 10-12 h,12-14h, 14-26 h, 26-50 h, 50-74 h after drug administration of dabigatran etexilate on Day 4 and Day 11.Population: PKS
For sum dabigatran: Ae0-74,ss (amount of the analyte excreted in urine at steady state over the time interval 0-74) on day 4 and day 11 if feasible. As per the protocol, day is counted as "Day 1 = 0:00"
Outcome measures
| Measure |
Dabigatran Etexilate+Idarucizumab
n=12 Participants
During the first part of the treatment period, dabigatran etexilate was administered alone. All subjects received 220 milligram (mg) dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 1 to 3) and a single 220 mg dose on Day 4. During the second part of the treatment period, after a washout period of 3 days, subjects again received dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 8 to 10) and a single 220 mg dose on Day 11. Idarucizumab (solution for infusion) 2 short infusions of 2.5 grams (g) each, with a 15 minute (min) interval was administered intravenously approximately 2 hours (h) after the last dabigatran etexilate administration.
|
|---|---|
|
For Sum Dabigatran: Amount of the Analyte Excreted in Urine at Steady State Over the Time Interval 0-74 Hours (Ae0-74,ss ) on Day 4 and Day 11
Day 4
|
11700 μg (microgram)
Geometric Coefficient of Variation 30.0
|
|
For Sum Dabigatran: Amount of the Analyte Excreted in Urine at Steady State Over the Time Interval 0-74 Hours (Ae0-74,ss ) on Day 4 and Day 11
Day 11
|
11000 μg (microgram)
Geometric Coefficient of Variation 41.8
|
SECONDARY outcome
Timeframe: Day 4: 74h, 74.5h, 75h, 76h, 78h, 80h, 84h; Day 11: 242h, 242.083h, 242.25h, 242.333h 243.333h, 244h, 246h, 248h, 252hPopulation: PKS
For unbound sum dabigatran: AUC 2-12,ss (Area under the concentration-time curve of the dabigatran in plasma at steady state over the time interval 2 hours-12 hours). As per the protocol, day is counted as "Day 1 = 0:00".
Outcome measures
| Measure |
Dabigatran Etexilate+Idarucizumab
n=12 Participants
During the first part of the treatment period, dabigatran etexilate was administered alone. All subjects received 220 milligram (mg) dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 1 to 3) and a single 220 mg dose on Day 4. During the second part of the treatment period, after a washout period of 3 days, subjects again received dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 8 to 10) and a single 220 mg dose on Day 11. Idarucizumab (solution for infusion) 2 short infusions of 2.5 grams (g) each, with a 15 minute (min) interval was administered intravenously approximately 2 hours (h) after the last dabigatran etexilate administration.
|
|---|---|
|
For Unbound Sum Dabigatran: Area Under the Concentration-time Curve of the Dabigatran in Plasma at Steady State Over the Time Interval 2 Hours-12 Hours
Day 4
|
1270 nanograms*hours/ milliliter
Geometric Coefficient of Variation 37.0
|
|
For Unbound Sum Dabigatran: Area Under the Concentration-time Curve of the Dabigatran in Plasma at Steady State Over the Time Interval 2 Hours-12 Hours
Day 11
|
11.6 nanograms*hours/ milliliter
Geometric Coefficient of Variation 44.3
|
Adverse Events
Dabigatran Etexilate+Idarucizumab
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Dabigatran Etexilate+Idarucizumab
n=12 participants at risk
During the first part of the treatment period, dabigatran etexilate was administered alone. All subjects received 220 milligram (mg) dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 1 to 3) and a single 220 mg dose on Day 4. During the second part of the treatment period, after a washout period of 3 days, subjects again received dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 8 to 10) and a single 220 mg dose on Day 11. Idarucizumab (solution for infusion) 2 short infusions of 2.5 grams (g) each, with a 15 minute (min)interval was administered intravenously approximately 2 hours (h) after the last dabigatran etexilate administration.
|
|---|---|
|
Vascular disorders
Haematoma
|
8.3%
1/12 • Adverse events from the first intake of treatment until the end of treatment visit; up to 23 days
|
|
Gastrointestinal disorders
Diarrhoea
|
8.3%
1/12 • Adverse events from the first intake of treatment until the end of treatment visit; up to 23 days
|
|
Investigations
Albumin urine present
|
100.0%
12/12 • Adverse events from the first intake of treatment until the end of treatment visit; up to 23 days
|
|
Investigations
Alpha 1 microglobulin increased
|
100.0%
12/12 • Adverse events from the first intake of treatment until the end of treatment visit; up to 23 days
|
|
Investigations
Protein urine present
|
91.7%
11/12 • Adverse events from the first intake of treatment until the end of treatment visit; up to 23 days
|
|
Investigations
Activated partial thromboplastin time prolonged
|
83.3%
10/12 • Adverse events from the first intake of treatment until the end of treatment visit; up to 23 days
|
|
Investigations
Urine electrophoresis abnormal
|
83.3%
10/12 • Adverse events from the first intake of treatment until the end of treatment visit; up to 23 days
|
|
Investigations
Prothrombin level decreased
|
33.3%
4/12 • Adverse events from the first intake of treatment until the end of treatment visit; up to 23 days
|
|
Investigations
Blood triglycerides increased
|
8.3%
1/12 • Adverse events from the first intake of treatment until the end of treatment visit; up to 23 days
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER