HealthyPhase 1NCT02028780

Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BI 655075 (Idarucizumab) Administered Alone or With Dabigatran Etexilate in Japanese Healthy Subjects

A Phase 1 study testing Idarucizumab and dabigatran in people with Healthy, run by Boehringer Ingelheim at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The primary objective is to investigate the safety, tolerability and pharmacokinetics of BI 655075 following intravenous administration of single rising doses of BI 655075 when administered alone and after administration of dabigatran. Read more about this study

Who is it for?: Ages 20 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Idarucizumab and dabigatran
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 80 participants
Where: 1 siteJapan
Study dates: Jan 2014to Aug 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 45 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

1. Healthy Japanese male subjects

Who cannot join

1. Any relevant deviation from healthy conditions

Trial locations and contacts

1 site in 1 country.

Japan1 site

1321.5.00001 Boehringer Ingelheim Investigational Site
Sumida-ku, Tokyo

Other trials in Japan

About this study

Official title: Randomised, Double-blind Within Dose Groups, Placebo-controlled Phase I Trial in Healthy Japanese Male Volunteers to Investigate Safety, Tolerability and Pharmacokinetics of Different Doses of BI 655075 (Part 1) and to Explore the Effective Dose of BI 655075 to Reverse Dabigatran Anticoagulant Activity (Part 2).

Conditions: Healthy
Being tested: Placebo to dose, Idarucizumab, Placebo to Idarucizumab, dabigatran

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Placebo to doseDrug
placebo
IdarucizumabDrug
short infusion
Placebo to IdarucizumabDrug
Placebo to Idarucizumab
dabigatranDrug
2 capsules dabigatran
IdarucizumabDrug
short infusion

Study groups in NCT02028780
Study group	Role	What they receive
Idarucizumab single doses	Experimental	different infusion durations Receives: Drug: Placebo to dose; Drug: Idarucizumab
Idarucizumab with dabigatran	Experimental	short infusion with 2 capsules dabigatran Receives: Drug: Idarucizumab; Drug: Placebo to Idarucizumab; Drug: dabigatran

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Subjects With Drug-related Adverse Events in Part 1 and Part 2
Percentage of subjects with drug-related adverse events in Part 1 and Part 2.
Measured: From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)

Secondary outcomes (7)

Ae0-74,ss on Days 4 and 11 for Sum Dabigatran (Part II)
Amount of analyte eliminated in urine at steady state from the time point 0 hours to time point 74 hours.
Measured: 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.
AUC2-12,ss on Days 4 and 11 for Unbound Sum Dabigatran (Part II).
Area under the concentration-time curve of the dabigatran in plasma at steady state over the time interval 2 hours-12 hours.
Time Frame: For dose group 5 to 7 (Day 1 to 3-Part-I):74hours (h), 74.5h, 75h, 76h, 78h, 80h, 82h, 84h, For dose group 8 (Day 1 to 3-Part-I): 74h, 74.5h, 75h, 76h, 78h, 80h, 82h, 84h and For dose group 5-7 (Day11 to Day13-Part II):242h, 242.167h, 242.5h, 243h, 244h,246h, 248h, 250h, 252h. For dose group 8 (Day11 to Day13-Part II):242h, 242.083h, 242.25h, 242.333h, 243.333h, 244h, 246h, 248h, 252h.
Measured: Day 4 (Part I) and Day 11 (Part II). Time frame are provided in detail in the Description section
Cmax for Idarucizumab in the Part I & Part II.
Maximum measured concentration of the analyte in plasma for idarucizumab Time frame: For dose group 1 to 3 (Day 1 to 3-Part-I): predose, 0 (end of infusion), 0.033h, 0.083h, 0.167h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h. For dose group 4 (Day 1 to 3-Part-I): predose, -0.5h, 0 (end of infusion), 0.033h, 0.083h, 0.167h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 48h. For dose group 5-7 (Day11 to Day13-Part II): predose, 242h (end of infusion), 242.033h, 242.083h, 242.167h, 242.25h, 242.5h, 242.75h, 243h, 243.5h, 244h, 244.5h, 245h, 246h, 248h, 250h, 252h, 254h, 258h, 266h, 290h.For dose group 8 (day11 to Day13-Part II): predose, 242h (end of infusion), 242.083h, 242.25h, 242.333h, 242.367h, 242.5h, 242.833h, 243.333h, 244h, 245h, 246h, 248h, 252h, 254h, 266h, 290h, 314h.
Measured: Day 1 to 3 (Part I) and Day 11 to 13 (Part II); Time frame are provided in detail in the Description section
AUC0-inf for Idarucizumab in the Part I & Part II.
Area under the concentration-time curve of the analyte in plasma for idarucizumab over the time interval from 0 extrapolated to infinity.
Time frame: For dose group 1 to 3 (Day 1 to 3-Part-I): predose, 0 (end of infusion), 0.033h, 0.083, 0.167h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h. For dose group 4 (Day 1 to 3-Part-I): predose, -0.5h, 0 (end of infusion), 0.033h, 0.083h, 0.167h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 48h. For dose group 5-7 (Day11 to Day13-Part II): predose, 242h (end of infusion), 242.033h, 242.083h, 242.167h, 242.25h, 242.5h, 242.75h, 243h, 243.5h, 244h, 244.5h, 245h, 246h, 248h, 250h, 252h, 254h, 258h, 266h, 290h.For dose group 8 (day11 to Day13-Part II): predose, 242h (end of infusion), 242.083h, 242.25h, 242.333h, 242.367h, 242.5h, 242.833h, 243.333h, 244h, 245h, 246h, 248h, 252h, 254h, 266h, 290h, 314h.
Measured: Day 1 to 3 (Part I) and Day 11 to 13 (Part II); Time frame are provided in detail in the Description section
Ae0-72 for Idarucizumab in the Part I & Part II.
Amount of idarucizumab eliminated in urine over the time interval 0-72. Time frame: For dose groups 1 to 3 (day1 to day4-Part-1):0-4 h, 4-8 h, 8-12 h, 12-24 h, 24-48 h, 48-72 h. For dose groups 5 to 7 (day 11 to day14-Part-II): 0-4 h, 4-8 h, 8-10 h, 10-12 h,12-24 h, 24-48 h, and 48-72 h. For dose groups 8 (day11 to day14-Part-II): 0-4h, 4-8 h, 8-10 h, 10-24 h, 24-48 h, 48-72 h.
Measured: Day 1 to 4 (Part I) and Day 11 to 14 (Part II); Time frame are provided in detail in the Description section
Ae0-73 for the Dose Group 4 in the Part I
Amount of the analyte excreted in urine over the time interval 0-73
Measured: For dose group 4 (day1 to day4-Part-1): 0-7h, 7-13h, 13-25h, 25-49h, 49-73h
AUEC2-12
Area under the effect curve over the time interval from 2 to 12h, AUEC2-12 on Days 4 and 11 for diluted thrombin time (dTT).
For dose groups 5 to 7(day4-Part-II): 74h, 74.5h, 75h, 76h, 78h, 80h, 82h, 84h on day 4. For dose groups 5 to 7(day11-Part-II): 242h, 242.083h, 242.167h, 242.5h, 243h, 244h, 246h, 248h, 250h, 252h. For dose groups 8(day4-Part-II): 74.5 h, 78 h, 84 h on day 4. For dose groups 8(day11-Part-II): 242h, 242.083h,242.25h, 242.333h, 243.333h, 244h, 246h, 248h, 252h on day 11.
AUEC is calculated by multiplying the ratio (Value at each time point/Ebase, unit of Vaue is [s] and Ebase is value [s] at baseline) by time. Therefore, Unit for AUEC2-12 is [h].
Measured: Day 4 and Day 11 (Part II); Time frame are provided in detail in the Description section

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2014Aug 2014

First posted7 Jan 2014 (estimated)
Study startJan 2014
Primary completionAug 2014
Study completionAug 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Enrolment: 80 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02028780
Sponsor's protocol ID: 1321.5
Status last verified: Jan 2016
First submitted: 6 Jan 2014
Last updated: 11 Feb 2016
Results posted: Yes, on ClinicalTrials.gov

Publications

Yasaka M, Ikushima I, Harada A, Imazu S, Taniguchi A, Norris S, Gansser D, Stangier J, Schmohl M, Reilly PA. Safety, pharmacokinetics and pharmacodynamics of idarucizumab, a specific dabigatran reversal agent in healthy Japanese volunteers: a randomized study. Res Pract Thromb Haemost. 2017 Aug 5;1(2):202-215. doi: 10.1002/rth2.12029. eCollection 2017 Oct.
PubMed 30046691
Norris S, Ramael S, Ikushima I, Haazen W, Harada A, Moschetti V, Imazu S, Reilly PA, Lang B, Stangier J, Glund S. Evaluation of the immunogenicity of the dabigatran reversal agent idarucizumab during Phase I studies. Br J Clin Pharmacol. 2017 Aug;83(8):1815-1825. doi: 10.1111/bcp.13269. Epub 2017 Apr 6.
PubMed 28230262

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 11 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomised, Double-blind Within Dose Groups, Placebo-controlled Phase I Trial in Healthy Japanese Male Volunteers to Investigate Safety, Tolerability and Pharmacokinetics of Different Doses of BI 655075 (Part 1) and to Explore the Effective Dose of BI 655075 to Reverse Dabigatran Anticoagulant Activity (Part 2).
ClinicalTrials.gov ID: NCT02028780
Acronym / sponsor ID: 1321.5
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 80 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Jan 2014
Primary completion: Aug 2014 (actual)
Study completion: Aug 2014 (actual)
First posted: 7 Jan 2014 (estimated)
Results: Posted 11 Feb 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Number of arms: 2

Arm	Type	Receives
Idarucizumab single doses	Experimental	Drug: Placebo to dose, Drug: Idarucizumabdifferent infusion durations
Idarucizumab with dabigatran	Experimental	Drug: Idarucizumab, Drug: Placebo to Idarucizumab, Drug: dabigatranshort infusion with 2 capsules dabigatran

Who may qualify

Ages: 20 to 45 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (1 listed)

1. Healthy Japanese male subjects

Key exclusion criteria (1 listed)

1. Any relevant deviation from healthy conditions

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Placebo to doseplacebo	Drug	Idarucizumab single doses
Idarucizumabshort infusion	Drug	Idarucizumab with dabigatran
Placebo to IdarucizumabPlacebo to Idarucizumab	Drug	Idarucizumab with dabigatran
dabigatran2 capsules dabigatran	Drug	Idarucizumab with dabigatran
Idarucizumabshort infusion	Drug	Idarucizumab single doses

Primary outcome

Percentage of Subjects With Drug-related Adverse Events in Part 1 and Part 2
Time frame: From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
Percentage of subjects with drug-related adverse events in Part 1 and Part 2.

7 secondary outcomes

Ae0-74,ss on Days 4 and 11 for Sum Dabigatran (Part II)
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.
AUC2-12,ss on Days 4 and 11 for Unbound Sum Dabigatran (Part II).
Time frame: Day 4 (Part I) and Day 11 (Part II). Time frame are provided in detail in the Description section
Cmax for Idarucizumab in the Part I & Part II.
Time frame: Day 1 to 3 (Part I) and Day 11 to 13 (Part II); Time frame are provided in detail in the Description section
AUC0-inf for Idarucizumab in the Part I & Part II.
Time frame: Day 1 to 3 (Part I) and Day 11 to 13 (Part II); Time frame are provided in detail in the Description section
Ae0-72 for Idarucizumab in the Part I & Part II.
Time frame: Day 1 to 4 (Part I) and Day 11 to 14 (Part II); Time frame are provided in detail in the Description section
Ae0-73 for the Dose Group 4 in the Part I
Time frame: For dose group 4 (day1 to day4-Part-1): 0-7h, 7-13h, 13-25h, 25-49h, 49-73h
AUEC2-12
Time frame: Day 4 and Day 11 (Part II); Time frame are provided in detail in the Description section

Results and safety

Results posted to the registry on 11 Feb 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo_5m (Part I)	6	6
Placebo_1h (Part I)	2	2
BI1000mg_5m (Dose group1 - Part I)	6	6
BI2000mg_5m (Dose group2 - Part I)	6	6
BI4000mg_5m (Dose group3 - Part I)	6	6
BI8000mg_1h (Dose group4 - Part I)	6	6
DE+Placebo_5m (Part II)	9	9
DE+Placebo+Placebo (Part II)	3	3
DE+1000mg_5m (Dose group5 - Part II)	9	9
DE+2000mg_5m (Dose group6 - Part II)	9	9
DE+4000mg_5m (Dose group7 - Part II)	9	9
DE+2500mg+2500mg (Dose group8 - Part II)	9	9

Primary outcome: Percentage of Subjects With Drug-related Adverse Events in Part 1 and Part 2

Time frame: From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II). Number. Unit: Percentage of participants

Measure	Placebo_5m (Part I) n = 6	Placebo_1h (Part I) n = 2	BI1000mg_5m (Dose group1 - Part I) n = 6	BI2000mg_5m (Dose group2 - Part I) n = 6	BI4000mg_5m (Dose group3 - Part I) n = 6	BI8000mg_1h (Dose group4 - Part I) n = 6	DE+Placebo_5m (Part II) n = 9	DE+Placebo+Placebo (Part II) n = 3	DE+1000mg_5m (Dose group5 - Part II) n = 9	DE+2000mg_5m (Dose group6 - Part II) n = 9	DE+4000mg_5m (Dose group7 - Part II) n = 9	DE+2500mg+2500mg (Dose group8 - Part II) n = 9
Value	16.7	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

Population analysed: Treated set (TS)

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo_5m (Part I)	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Placebo_1h (Part I)	0 of 2 (0%)	0 of 2 (0%)	Not reported
BI1000mg_5m (Dose group1 - Part I)	0 of 6 (0%)	0 of 6 (0%)	Not reported
BI2000mg_5m (Dose group2 - Part I)	0 of 6 (0%)	0 of 6 (0%)	Not reported
BI4000mg_5m (Dose group3 - Part I)	0 of 6 (0%)	0 of 6 (0%)	Not reported
BI8000mg_1h (Dose group4 - Part I)	0 of 6 (0%)	0 of 6 (0%)	Not reported
DE+Placebo_5m (Part II)	0 of 9 (0%)	0 of 9 (0%)	Not reported
DE+Placebo+Placebo (Part II)	0 of 3 (0%)	0 of 3 (0%)	Not reported
DE+1000mg_5m (Dose group5 - Part II)	0 of 9 (0%)	0 of 9 (0%)	Not reported
DE+2000mg_5m (Dose group6 - Part II)	0 of 9 (0%)	0 of 9 (0%)	Not reported
DE+4000mg_5m (Dose group7 - Part II)	0 of 9 (0%)	0 of 9 (0%)	Not reported
DE+2500mg+2500mg (Dose group8 - Part II)	0 of 9 (0%)	0 of 9 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30046691Yasaka M, Ikushima I, Harada A, Imazu S, Taniguchi A, Norris S, Gansser D, Stangier J, Schmohl M, Reilly PA. Safety, pharmacokinetics and pharmacodynamics of idarucizumab, a specific dabigatran reversal agent in healthy Japanese volunteers: a randomized study. Res Pract Thromb Haemost. 2017 Aug 5;1(2):202-215. doi: 10.1002/rth2.12029. eCollection 2017 Oct.
Derived from this study: PubMed 28230262Norris S, Ramael S, Ikushima I, Haazen W, Harada A, Moschetti V, Imazu S, Reilly PA, Lang B, Stangier J, Glund S. Evaluation of the immunogenicity of the dabigatran reversal agent idarucizumab during Phase I studies. Br J Clin Pharmacol. 2017 Aug;83(8):1815-1825. doi: 10.1111/bcp.13269. Epub 2017 Apr 6.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Idarucizumab and dabigatran in people with Healthy, run by Boehringer Ingelheim at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Subjects With Drug-related Adverse Events in Part 1 and Part 2 (time frame: From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02028780, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2016.