Healthy VolunteersPhase 1NCT03086356
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
A Phase 1 study testing Dabigatran etexilate and Idarucizumab in people with Healthy Volunteers, run by Boehringer Ingelheim at 1 site in China.
Trial summary
The primary objective of the trial is to investigate the pharmacokinetics and pharmacodynamics of idarucizumab in Chinese healthy male and female subjects following intravenous administration of idarucizumab followed by idarucizumab with 15 minutes interval when administered at or close to the steady state of… Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Dabigatran etexilate and Idarucizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- 10 May 2017to 12 Sep 2017
- 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
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age >= 18 and Age <= 45 years at screening
- Healthy male and female based upon a complete medical history, including vital signs (Blood Pressure, Pulse Rate, and Body Temperature), 12-lead Electrocardiogram and clinical laboratory tests. Women of childbearing potential must be ready and able to use highly effective methods of birth control per International Committee on Harmonisation M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
- Body weight >=50 kg with body mass index range >=19.0 and <24.0 kg/m2 at Visit 1.
- Signed and dated written informed consent in accordance with Good Clinical Practice and local legislation prior to admission to the trial.
Who cannot join
- Any finding of the medical examination (including Blood Pressure, Pulse Rate, Body Temperature and Electrocardiogram) is deviating from normal and judged as clinically relevant by the investigator
- Any evidence of a clinically relevant concomitant disease according to investigator's clinical judgement
- Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication (except appendectomy)
- Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
- History of relevant orthostatic hypotension, fainting spells or blackouts.
Show all 30Show fewer
- Chronic or relevant acute infections
- History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) or immune system disease
- Intake of drugs with a long half-life (> 24 hours) within at least 30 days or less than 10 half-lives of the respective drug prior to first trial drug administration
- Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/corrected QT (QTc) interval.
- Participation in another trial with investigational drug administration within 60 days prior to first trial drug administration
- Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
- Inability to refrain from smoking during hospitalization
- Alcohol abuse (consumption of more than 20 g per day: e.g., 1 middle-sized bottles of beer, 1 gou [equivalent to 180 mL] of sake))
- Drug abuse or positive drug screening
- Blood donation (400 mL whole blood donation within 12 weeks, 200 mL whole blood donation or blood component donation within 4 weeks) prior to first trial drug administration
- Intention to perform excessive physical activities within one week prior to first trial drug administration or during the trial
- Any laboratory values outside the reference range that are of clinical relevance according to investigator's clinical judgement
- Inability to comply with dietary regimen of trial site
- A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTcF interval >450 ms)
- A history of additional risk factors for torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
- Positive HIV (human immunodeficiency virus) test result at screening examination
- Positive testing for Hepatitis B Antigen and/or a positive Hepatitis C antibody test result at screening examination
- Subjects considered unsuitable for inclusion by the investigator, e.g. are unable to understand and comply with trial requirements, or have any condition which in the opinion of the investigator would not allow safe participation in the trial.
- Subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until 12 weeks after the trial completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female (intra-uterine device with spermicide. hormonal contraceptive since at least 8 weeks)
- History or evidence of blood dyscrasia, haemorrhagic diathesis, severe thrombocytopenia, cerebrovascular haemorrhage, bleeding tendencies associated with active ulceration or overt bleeding of gastrointestinal, respiratory or genitourinary tract or any disease or condition with haemorrhagic tendencies (e.g. cerebral aneurysm, dissecting aorta, central nervous system (CNS) trauma, retinopathy, nephrolithiasis)
- Abnormal values for prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombocytes considered by the investigator or one of the co-investigators to be clinically relevant
- Creatinine and estimated glomerular filtration rate (GFR) outside the normal range
- Evidence of proteinuria
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Open Label Phase I Trial in Healthy Chinese Male and Female Volunteers to Investigate Pharmacokinetics and Pharmacodynamics of Idarucizumab to Reverse Dabigatran Anticoagulant Activity
The primary objective of the trial is to investigate the pharmacokinetics and pharmacodynamics of idarucizumab in Chinese healthy male and female subjects following intravenous administration of idarucizumab followed by idarucizumab with 15 minutes interval when administered at or close to the steady state of dabigatran.
Another objective of this trial is to explore the effect idarucizumab on the PK (pharmacokinetic(s)) and PD (pharmacodynamic) parameters of dabigatran.
- Conditions
- Healthy Volunteers
- Being tested
- Dabigatran etexilate, Idarucizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dabigatran etexilateDrug
Also called PRADAXA, PRAZAXA
Days 1-4 and Day 8-11
IdarucizumabDrug
Also called PRAXBIND, Praxbind, Prizbind
Day 11
| Study group | Role | What they receive |
|---|---|---|
| All Subjects | Experimental | Dabigatran etexilate alone (days 1-4) and (days 8-10) and with Idarucizumab (day 11) Receives: Drug: Dabigatran etexilate; Drug: Idarucizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Measured Concentration of Idarucizumab in Plasma (Cmax)
Cmax, maximum measured concentration of idarucizumab in plasma
Measured: -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)
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
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 %)
Measured: Day 4 and day 11
Area Under the Concentration-time Curve of Idarucizumab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
AUC0-∞, area under the concentration-time curve of idarucizumab in plasma over the time interval from 0 extrapolated to infinity
Measured: -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)
Amount of Idarucizumab Eliminated in Urine Over the Time Interval From 0 to 72 Hours (h) (Ae0-72)
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"
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
Secondary outcomes (2)
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
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"
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.
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
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".
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2017
- Study start10 May 2017
- Primary completion12 Sep 2017
- Study completion12 Sep 2017
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 (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03086356
- Sponsor's protocol ID
- 1321.6
- Status last verified
- Mar 2019
- First submitted
- 16 Mar 2017
- Last updated
- 8 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Wang Z, Zhao X, He P, Chen S, Jiang J, Harada A, Brooks S, Cui Y. Idarucizumab Reverses Dabigatran Anticoagulant Activity in Healthy Chinese Volunteers: A Pharmacokinetics, Pharmacodynamics, and Safety Study. Adv Ther. 2020 Sep;37(9):3916-3928. doi: 10.1007/s12325-020-01439-2. Epub 2020 Jul 20.
PubMed 32691242
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Phase I Trial in Healthy Chinese Male and Female Volunteers to Investigate Pharmacokinetics and Pharmacodynamics of Idarucizumab to Reverse Dabigatran Anticoagulant Activity
- ClinicalTrials.gov ID
- NCT03086356
- Acronym / sponsor ID
- 1321.6
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 10 May 2017 (actual)
- Primary completion
- 12 Sep 2017 (actual)
- Study completion
- 12 Sep 2017 (actual)
- First posted
- 22 Mar 2017 (actual)
- Results
- Posted 8 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the trial is to investigate the pharmacokinetics and pharmacodynamics of idarucizumab in Chinese healthy male and female subjects following intravenous administration of idarucizumab followed by idarucizumab with 15 minutes interval when administered at or close to the steady state of dabigatran.
Another objective of this trial is to explore the effect idarucizumab on the PK (pharmacokinetic(s)) and PD (pharmacodynamic) parameters of dabigatran.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Subjects | Experimental | Drug: Dabigatran etexilate, Drug: IdarucizumabDabigatran etexilate alone (days 1-4) and (days 8-10) and with Idarucizumab (day 11) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age >= 18 and Age <= 45 years at screening
- Healthy male and female based upon a complete medical history, including vital signs (Blood Pressure, Pulse Rate, and Body Temperature), 12-lead Electrocardiogram and clinical laboratory tests. Women of childbearing potential must be ready and able to use highly effective methods of birth control per International Committee on Harmonisation M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
- Body weight >=50 kg with body mass index range >=19.0 and <24.0 kg/m2 at Visit 1.
- Signed and dated written informed consent in accordance with Good Clinical Practice and local legislation prior to admission to the trial.
Key exclusion criteria (30 listed)
- Any finding of the medical examination (including Blood Pressure, Pulse Rate, Body Temperature and Electrocardiogram) is deviating from normal and judged as clinically relevant by the investigator
- Any evidence of a clinically relevant concomitant disease according to investigator's clinical judgement
- Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication (except appendectomy)
- Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
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 etexilateAlso: PRADAXA, PRAZAXADays 1-4 and Day 8-11 | Drug | All Subjects |
| IdarucizumabAlso: PRAXBIND, Praxbind, PrizbindDay 11 | Drug | All Subjects |
Primary outcome
Maximum Measured Concentration of Idarucizumab in Plasma (Cmax)
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)
Cmax, maximum measured concentration of idarucizumab in plasma
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
Time frame: Day 4 and day 11
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 %)
Area Under the Concentration-time Curve of Idarucizumab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
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)
AUC0-∞, area under the concentration-time curve of idarucizumab in plasma over the time interval from 0 extrapolated to infinity
Amount of Idarucizumab Eliminated in Urine Over the Time Interval From 0 to 72 Hours (h) (Ae0-72)
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
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"
2 secondary outcomes
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.
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32691242Wang Z, Zhao X, He P, Chen S, Jiang J, Harada A, Brooks S, Cui Y. Idarucizumab Reverses Dabigatran Anticoagulant Activity in Healthy Chinese Volunteers: A Pharmacokinetics, Pharmacodynamics, and Safety Study. Adv Ther. 2020 Sep;37(9):3916-3928. doi: 10.1007/s12325-020-01439-2. Epub 2020 Jul 20.
- Related InfoLink provided by the sponsor.
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Screening Protocol
Pain
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 etexilate and Idarucizumab in people with Healthy Volunteers, run by Boehringer Ingelheim at 1 site in China.
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 4 inclusion and 30 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 8 Mar 2019. 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 China. 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 8 Mar 2019). 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?
Maximum Measured Concentration of Idarucizumab in Plasma (Cmax) (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)). The study lists 4 primary outcomes in all. 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 NCT03086356, which also lists 1 linked publication.
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 8 Mar 2019.