HealthyPhase 1NCT01688830

Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BI 655075 Administered Alone or With Dabigatran Etexilate

A Phase 1 study testing Dabigatran and BI 655075 in people with Healthy, run by Boehringer Ingelheim at 1 site in Belgium.

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 18 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Dabigatran and BI 655075
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 157 participants
Where: 1 siteBelgium
Study dates: Sep 2012to Nov 2013
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 18 to 45 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

1. Healthy male subjects

Who cannot join

1. Any relevant deviation from healthy conditions

Trial locations and contacts

1 site in 1 country.

Belgium1 site

1321.1.1 Boehringer Ingelheim Investigational Site
Antwerp

Other trials in Belgium

About this study

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

Conditions: Healthy
Being tested: Dabigatran, BI 655075, Placebo

What participants receive

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

DabigatranDrug
BI 655075Drug
PlaceboDrug

Study groups in NCT01688830
Study group	Role	What they receive
BI 655075	Experimental	Not described Receives: Drug: BI 655075
Placebo	Placebo comparator	Not described Receives: Drug: Placebo
BI 655075 with dabigatran	Experimental	Not described Receives: Drug: Dabigatran; Drug: BI 655075

What is being measured

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

Number of Subjects With Drug Related Adverse Events (AE)
Frequency of subjects with related adverse events (AE) by treatment
Measured: AEs occurring until end of follow-up (Up to 3 months after last drug administration)

Secondary outcomes (9)

Cmax (Maximum Measured Concentration) for Idarucizumab
Cmax (maximum measured concentration) for idarucizumab
Measured: -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h
Tmax (Time From Dosing to Maximum Measured Concentration) for Idarucizumab
tmax (time from dosing to maximum measured concentration) for idarucizumab
Measured: -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h
AUC0-inf (Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity) for Idarucizumab
AUC0-inf (area under the concentration-time curve from time 0 extrapolated to infinity) for idarucizumab
Measured: -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h
Aet1-t2 (Amount of Idarucizumab Eliminated in Urine From Time Point t1 to Time Point t2)
Aet1-t2 (amount of idarucizumab eliminated in urine from time point t1 to time point t2)
Ae(0-7h) is presented for dose groups with 1 h infusion and Ae(0-4h) is presented for dose groups with 5 min infusion.
Measured: Up to 7 hours
Aet1-t2,ss (Amount of Dabigatran Etexilate Eliminated in Urine From Time Point t1 to Time Point t2, at Steady State) on Day 3 and Day 4 for Sum Dabigatran
Aet1-t2,ss (amount of dabigatran etexilate eliminated in urine from time point t1 to time point t2, at steady state) on Day 3 and Day 4
Ae(0-12h,ss) of sum dabigatran
Measured: Intervals 0-2, 2-6, 6-10, 10-12 hours on Day 3 post dabigatran treatment and -2 to -0:05, -0:05 to 4, 4-8, 8-10, 10-12, 12-24, 24-48, 48-72 on Day 4 post Idarucizumab treatment
C1.92,ss, C2,ss, C2.5,ss, C6,ss, and C12,ss (Concentration of the Unbound Sum Dabigatran in Plasma at Steady State)
Concentrations of unbound sum dabigatran in plasma after 1.92 to 12 h, at steady state of dabigatran, on Day 4 are presented.
The endpoint refers to unbound sum dabigatran at several time points. The intended pharmacodynamic effect of idarucizumab is to reduce the concentration of this measure to levels below the lower limit of quantification (BLQ). "BLQ" values are not considered in the calculation of descriptive statistics; and therefore bias the result. This is the reason for applying the 2/3 rule to obtain reliable results. 2/3 rule states that, Statistics of PK parameters are only estimated when at least 2/3 of the data are evaluable.
Measured: 1.92 hours (h), 2 h, 2.5 h, 6 h and 12 h on Day 4
AUCt1-t2,ss (Area Under the Concentration-time Curve for the Unbound Sum Dabigatran in Plasma From Time Point t1 to Time Point t2, at Steady State) on Day 3 and Day 4
AUC(2-12),ss ((area under the concentration-time curve for the idarucizumab in plasma from time point 2 to 12 h )) on Day 3 and Day 4
Measured: 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h
AUECt1-t2 (Area Under the Effect Curve From Time Point t1 to Time Point t2) on Day 3 and Day 4 (Determined Under Consideration of the Baseline Value) for Part 2 of the Study
AUECt1-t2 (area under the effect curve from time point t1=2 hours to time point t2=12 hours) on Day 3 and Day 4 (determined under consideration of the baseline value).
Ratio of above baseline AUEC(2-12) on Day 4 to above baseline AUEC(2-12) on Day 3 is presented.
This endpoint was determined for Activated Partial Thromboplastin time (aPTT), Dithiothreitol (dTT), Thrombin time (TT) and Ecarin clotting time (ECT)
Measured: 2hours-12 hours
AUECt1-t2 (Area Under the Effect Curve From Time Point t1 to Time Point t2) on Day 3 and Day 4 (Determined Under Consideration of the Baseline Value) for Part 3 of the Study
AUECt1-t2 (area under the effect curve from time point t1=2 hours to time point t2=12 hours) on Day 3 and Day 4 (determined under consideration of the baseline value).
Ratio of above baseline AUEC(2-12) on Day 4 to above baseline AUEC(2-12) on Day 3 is presented.
This endpoint was determined for Activated Partial Thromboplastin time (aPTT) and Dithiothreitol (dTT)
Measured: 2hours-12 hours

Timeline

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

Sep 2012Nov 2013

First posted20 Sep 2012 (estimated)
Study startSep 2012
Primary completionNov 2013
Study completionNov 2013

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: 157 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01688830
Sponsor's protocol ID: 1321.1
Other IDs: 2012-003611-66
Status last verified: May 2016
First submitted: 17 Sep 2012
Last updated: 23 Jun 2016
Results posted: Yes, on ClinicalTrials.gov

Publications

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
Glund S, Stangier J, Schmohl M, Gansser D, Norris S, van Ryn J, Lang B, Ramael S, Moschetti V, Gruenenfelder F, Reilly P, Kreuzer J. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet. 2015 Aug 15;386(9994):680-90. doi: 10.1016/S0140-6736(15)60732-2. Epub 2015 Jun 15.
PubMed 26088268

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 23 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomised, Double-blind, Placebo-controlled Phase I Study in Healthy Male Volunteers. to Investigate Safety, Tolerability and Pharmacokinetics of Single Rising Doses of BI 655075 (Part 1) and to Explore the Dose of BI 655075 Effective to Reverse Dabigatran Anticoagulant Activity (Part 2)
ClinicalTrials.gov ID: NCT01688830
Acronym / sponsor ID: 1321.1
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 157 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Sep 2012
Primary completion: Nov 2013 (actual)
Study completion: Nov 2013 (actual)
First posted: 20 Sep 2012 (estimated)
Results: Posted 15 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: 3

Arm	Type	Receives
BI 655075	Experimental	Drug: BI 655075
Placebo	Placebo comparator	Drug: Placebo
BI 655075 with dabigatran	Experimental	Drug: Dabigatran, Drug: BI 655075

Who may qualify

Ages: 18 to 45 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (1 listed)

1. Healthy 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
Dabigatran	Drug	BI 655075 with dabigatran
BI 655075	Drug	BI 655075, BI 655075 with dabigatran
Placebo	Drug	Placebo

Primary outcome

Number of Subjects With Drug Related Adverse Events (AE)
Time frame: AEs occurring until end of follow-up (Up to 3 months after last drug administration)
Frequency of subjects with related adverse events (AE) by treatment

9 secondary outcomes

Cmax (Maximum Measured Concentration) for Idarucizumab
Time frame: -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h
Tmax (Time From Dosing to Maximum Measured Concentration) for Idarucizumab
Time frame: -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h
AUC0-inf (Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity) for Idarucizumab
Time frame: -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h
Aet1-t2 (Amount of Idarucizumab Eliminated in Urine From Time Point t1 to Time Point t2)
Time frame: Up to 7 hours
Aet1-t2,ss (Amount of Dabigatran Etexilate Eliminated in Urine From Time Point t1 to Time Point t2, at Steady State) on Day 3 and Day 4 for Sum Dabigatran
Time frame: Intervals 0-2, 2-6, 6-10, 10-12 hours on Day 3 post dabigatran treatment and -2 to -0:05, -0:05 to 4, 4-8, 8-10, 10-12, 12-24, 24-48, 48-72 on Day 4 post Idarucizumab treatment
C1.92,ss, C2,ss, C2.5,ss, C6,ss, and C12,ss (Concentration of the Unbound Sum Dabigatran in Plasma at Steady State)
Time frame: 1.92 hours (h), 2 h, 2.5 h, 6 h and 12 h on Day 4
AUCt1-t2,ss (Area Under the Concentration-time Curve for the Unbound Sum Dabigatran in Plasma From Time Point t1 to Time Point t2, at Steady State) on Day 3 and Day 4
Time frame: 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h
AUECt1-t2 (Area Under the Effect Curve From Time Point t1 to Time Point t2) on Day 3 and Day 4 (Determined Under Consideration of the Baseline Value) for Part 2 of the Study
Time frame: 2hours-12 hours
AUECt1-t2 (Area Under the Effect Curve From Time Point t1 to Time Point t2) on Day 3 and Day 4 (Determined Under Consideration of the Baseline Value) for Part 3 of the Study
Time frame: 2hours-12 hours

Results and safety

Results posted to the registry on 15 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 1 h	21	21
20 mg Idarucizumab 1h	6	6
60 mg Idarucizumab 1h	6	6
200 mg Idarucizumab 1h	6	6
600 mg Idarucizumab 1h	5	5
1.2 g Idarucizumab 1h	6	6
2 g Idarucizumab 1h	12	12
3 g Idarucizumab 1h	6	6
4 g Idarucizumab 1h	6	6
6 g Idarucizumab 1h	6	6
8 g Idarucizumab 1h	6	5
Placebo 5min	6	6
1 g Idarucizumab 5min	6	6
2 g Idarucizumab 5min	6	6
4 g Idarucizumab 5min	6	6
DE+ Placebo 5min	9	9
DE+ 1 g Idarucizumab 5min	9	9
DE+ 2 g Idarucizumab 5min	9	9
DE+ 4 g Idarucizumab 5min	8	8
DE+ Placebo+ Placebo	3	3
DE+ 5 g + 2.5 g Idarucizumab	9	9

Primary outcome: Number of Subjects With Drug Related Adverse Events (AE)

Time frame: AEs occurring until end of follow-up (Up to 3 months after last drug administration). Number. Unit: participants

Measure	Placebo 1 h n = 21	20 mg Idarucizumab 1h n = 6	60 mg Idarucizumab 1h n = 6	200 mg Idarucizumab 1h n = 6	600 mg Idarucizumab 1h n = 5	1.2 g Idarucizumab 1h n = 6	2 g Idarucizumab 1h n = 12	3 g Idarucizumab 1h n = 6	4 g Idarucizumab 1h n = 6	6 g Idarucizumab 1h n = 6	8 g Idarucizumab 1h n = 6	Placebo 5min n = 6	1 g Idarucizumab 5min n = 6	2 g Idarucizumab 5min n = 6	4 g Idarucizumab 5min n = 6	DE+ Placebo 5min n = 9	DE+ 1 g Idarucizumab 5min n = 9	DE+ 2 g Idarucizumab 5min n = 9	DE+ 4 g Idarucizumab 5min n = 8	DE+ Placebo+ Placebo n = 3	DE+ 5 g + 2.5 g Idarucizumab n = 9
Value	2	0	0	0	0	0	2	0	0	0	1	0	0	0	0	0	1	0	0	1	1

Population analysed: Treated set

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs occurring until end of follow-up (Up to 3 months after last drug administration). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo 1 h	0 of 21 (0%)	7 of 21 (33.3%)	Not reported
20 mg Idarucizumab 1h	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
60 mg Idarucizumab 1h	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
200 mg Idarucizumab 1h	0 of 6 (0%)	5 of 6 (83.3%)	Not reported
600 mg Idarucizumab 1h	0 of 5 (0%)	2 of 5 (40%)	Not reported
1.2 g Idarucizumab 1h	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
2 g Idarucizumab 1h	0 of 12 (0%)	4 of 12 (33.3%)	Not reported
3 g Idarucizumab 1h	0 of 6 (0%)	3 of 6 (50%)	Not reported
4 g Idarucizumab 1h	0 of 6 (0%)	0 of 6 (0%)	Not reported
6 g Idarucizumab 1h	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
8 g Idarucizumab 1h	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
Placebo 5min	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
1 g Idarucizumab 5min	0 of 6 (0%)	3 of 6 (50%)	Not reported
2 g Idarucizumab 5min	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
4 g Idarucizumab 5min	0 of 6 (0%)	3 of 6 (50%)	Not reported
DE (Dose Groups 14-16)	0 of 35 (0%)	20 of 35 (57.1%)	Not reported
DE+ Placebo 5min	0 of 9 (0%)	1 of 9 (11.1%)	Not reported
DE+ 1 g Idarucizumab 5min	0 of 9 (0%)	4 of 9 (44.4%)	Not reported
DE+ 4 g Idarucizumab 5min	0 of 8 (0%)	4 of 8 (50%)	Not reported

Limitations and caveats (from the sponsor): There is only one group of subjects in study part 3 receiving active treatment. However, AE table displays the AEs occurring in different phases separately.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
Derived from this study: PubMed 26088268Glund S, Stangier J, Schmohl M, Gansser D, Norris S, van Ryn J, Lang B, Ramael S, Moschetti V, Gruenenfelder F, Reilly P, Kreuzer J. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet. 2015 Aug 15;386(9994):680-90. doi: 10.1016/S0140-6736(15)60732-2. Epub 2015 Jun 15.

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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 Dabigatran and BI 655075 in people with Healthy, run by Boehringer Ingelheim at 1 site in Belgium.

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 23 Jun 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 Belgium. 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. Some participants in this study may receive a placebo. 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 15 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?

Number of Subjects With Drug Related Adverse Events (AE) (time frame: AEs occurring until end of follow-up (Up to 3 months after last drug administration)). 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 NCT01688830, 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 23 Jun 2016.