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Trial record 17 of 333 for:    DABIGATRAN

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

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ClinicalTrials.gov Identifier: NCT03086356
Recruitment Status : Completed
First Posted : March 22, 2017
Results First Posted : March 8, 2019
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy Volunteers
Interventions Drug: Dabigatran etexilate
Drug: Idarucizumab
Enrollment 12
Recruitment Details 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.
Pre-assignment Details

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.

Arm/Group Title Dabigatran Etexilate+Idarucizumab
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 12
Completed 12
Not Completed 0
Arm/Group Title Dabigatran Etexilate+Idarucizumab
Hide Arm/Group Description 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 Number of Baseline Participants 12
Hide Baseline Analysis Population Description
Treated set (TS): The TS included all subjects who received at least 1 infusion of idarucizumab.
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants
35.6  (5.8)
[1]
Measure Description: Age at the time of informed consent
[2]
Measure Analysis Population Description: TS
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Female
6
  50.0%
Male
6
  50.0%
[1]
Measure Analysis Population Description: TS
Race (NIH/OMB)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
American Indian or Alaska Native
0
   0.0%
Asian
12
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
0
   0.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
[1]
Measure Description: Ethnicity is not reported in this trial
[2]
Measure Analysis Population Description: TS
1.Primary Outcome
Title Maximum Measured Concentration of Idarucizumab in Plasma (Cmax)
Hide Description Cmax, maximum measured concentration of idarucizumab in plasma
Time Frame -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)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic set (PKS): The PKS included all subjects of the Treated set (TS) who had at least one Pharmacokinetic (PK) parameter analysed.
Arm/Group Title Dabigatran Etexilate+Idarucizumab
Hide Arm/Group Description:
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 Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanomoles (nmol) per litre (L)
30900
(9.86%)
2.Primary Outcome
Title 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
Hide Description

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 %)

Time Frame Day 4 and day 11
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Dabigatran Etexilate+Idarucizumab
Hide Arm/Group Description:
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 Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: hours
Day 4 8.23  (32.0)
Day 11 0.118  (140)
3.Primary Outcome
Title Area Under the Concentration-time Curve of Idarucizumab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Hide Description AUC0-∞, area under the concentration-time curve of idarucizumab in plasma over the time interval from 0 extrapolated to infinity
Time Frame -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)
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Dabigatran Etexilate+Idarucizumab
Hide Arm/Group Description:
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 Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanomoles (nmol)*hours (h) per litre (L)
44200
(10.1%)
4.Primary Outcome
Title Amount of Idarucizumab Eliminated in Urine Over the Time Interval From 0 to 72 Hours (h) (Ae0-72)
Hide Description

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"

Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Dabigatran Etexilate+Idarucizumab
Hide Arm/Group Description:
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 Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micromole (μmol)
35.3
(57.1%)
5.Secondary Outcome
Title 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
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Dabigatran Etexilate+Idarucizumab
Hide Arm/Group Description:
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 Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg (microgram)
Day 4
11700
(30.0%)
Day 11
11000
(41.8%)
6.Secondary Outcome
Title 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
Hide Description

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".

Time Frame Day 4: 74h, 74.5h, 75h, 76h, 78h, 80h, 84h; Day 11: 242h, 242.083h, 242.25h, 242.333h 243.333h, 244h, 246h, 248h, 252h
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Dabigatran Etexilate+Idarucizumab
Hide Arm/Group Description:
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 Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms*hours/ milliliter
Day 4
1270
(37.0%)
Day 11
11.6
(44.3%)
Time Frame Adverse events from the first intake of treatment until the end of treatment visit; up to 23 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dabigatran Etexilate+Idarucizumab
Hide Arm/Group Description 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.
All-Cause Mortality
Dabigatran Etexilate+Idarucizumab
Affected / at Risk (%)
Total   0/12 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Dabigatran Etexilate+Idarucizumab
Affected / at Risk (%)
Total   0/12 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dabigatran Etexilate+Idarucizumab
Affected / at Risk (%)
Total   12/12 (100.00%) 
Gastrointestinal disorders   
Diarrhoea  1  1/12 (8.33%) 
Investigations   
Albumin urine present  1  12/12 (100.00%) 
Alpha 1 microglobulin increased  1  12/12 (100.00%) 
Protein urine present  1  11/12 (91.67%) 
Activated partial thromboplastin time prolonged  1  10/12 (83.33%) 
Urine electrophoresis abnormal  1  10/12 (83.33%) 
Prothrombin level decreased  1  4/12 (33.33%) 
Blood triglycerides increased  1  1/12 (8.33%) 
Vascular disorders   
Haematoma  1  1/12 (8.33%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03086356     History of Changes
Other Study ID Numbers: 1321.6
First Submitted: March 16, 2017
First Posted: March 22, 2017
Results First Submitted: September 12, 2018
Results First Posted: March 8, 2019
Last Update Posted: March 8, 2019