Drug InteractionPhase 1NCT02560688
Phase 1 Study to Evaluate the Safety and Tolerability of DS-1040b IV Infusion With Clopidogrel in Healthy Subjects
A Phase 1 study testing DS-1040b and Clopidogrel in people with Drug Interaction, run by Daiichi Sankyo at 1 site in United Kingdom.
Trial summary
This study is being conducted to test the hypothesis that coadministration of clopidogrel with DS-1040b will be safe and well tolerated. Subjects entering the study will initially receive a single 12 hour infusion of DS-1040b, to generate data on the effect of DS-1040b alone. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Interaction
- What is being tested?
- DS-1040b and Clopidogrel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2015to Mar 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female subjects of non-childbearing potential; subjects must be aged 18 years to 60 years, inclusive.
- Subjects with a body mass index (BMI) of 18 kg/m2 to 30 kg/m2, inclusive, and weighing between 50 kg and 100 kg, inclusive. BMI is calculated as weight [kg]/(height [m])*2.
- Subjects must be in good health as determined by medical history, physical examination and Screening investigations, and taking no regular medication.
- Female subjects must be of non-childbearing potential as follows:
- Must be postmenopausal (the last menstrual period was at least 12 months before Screening, and a follicle-stimulating hormone [FSH] test at Screening confirms postmenopausal status); or
- Must be surgically sterile having undergone hysterectomy, bilateral oophorectomy, bilateral salpingectomy and/or bilateral tubal ligation.
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- Willing to comply with all study restrictions, including the use of contraception, concomitant medication and dietary and lifestyle restrictions.
- Possessing sufficient intelligence to understand the nature of the study and any hazards of participating in it, and the ability to communicate satisfactorily with the Investigator and to participate in, and comply with the requirements of, the entire study.
- Has given written consent to participate after reading the informed consent form (ICF), and after having the opportunity to discuss the study with the Investigator or his/her delegate.
- Have given written consent to have his/her data entered into The Overvolunteering Prevention System.
Who cannot join
- Clinically relevant abnormal history, physical findings, ECG findings or laboratory values that could interfere with the objectives of the study or the safety of the subject.
- Presence or history of acute or chronic illness, including (but not limited to) liver or kidney disease, hypertension, seizures, or any known impairment of endocrine, or other specific body-organ dysfunction.
- Presence or history of severe adverse reaction to any medicine.
- Presence or history of malignant disease.
- Surgery (eg, stomach bypass) or medical condition that might affect absorption of medicines.
- Significant illness within 4 weeks before the dose of study medication.
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- Participation in another clinical trial of a new chemical entity or a prescription medicine within the previous 3 months, or unwilling to abstain from participating in other clinical trials during the study and for 3 months after receipt of study medication.
- Participation in another clinical study with DS-1040b.
- Day-1 bleeding time greater than 10 minutes.
- Blood pressure (BP) and heart rate (HR) in semi-supine position at the Screening examination outside the ranges 90 to 140 mmHg systolic, 40 to 90 mmHg diastolic; HR 40 to 100 beats/min. A subject with vital signs outside the reference range for the population being studied may be included at the Investigator's discretion if it is unlikely to introduce additional risk factors and will not interfere with study procedures.
- Abnormal electrocardiogram ECG waveform morphology at Screening that would preclude accurate measurement of the uncorrected QT interval (QT) duration.
- QT interval for HR corrected using Fridericia's formula (QTcF) interval duration > 430 msec for men or > 450 msec for women, obtained as an average from the measurements on triplicate Screening ECGs.
- Use of any prescription medicine, over-the-counter (OTC) medications, herbal remedies (such as St John's Wort), or food known to be strong inhibitors or strong inducers of CYP enzymes during the 30 days before the dose of study medication; use of any other prescription or OTC medicine (except as permitted, including dietary supplements or herbal remedies, during the 7 days before the first dose of study medication.
- Consumption of certain foods or beverages before the dose and throughout the study period.
- Loss of more than 400 mL blood plasma, platelets or any other blood components during the 3 months before the first dose of study medication, or unwilling to abstain from doing so during the study and for 3 months after receipt of study medication.
- Abuse of drugs or alcohol in the past, or intake of more than 21 units of alcohol weekly (for males) or 14 units of alcohol weekly (for females).
- Use of tobacco products or nicotine-containing products during the 3 months before the dose of study medication.
- Male subjects not using adequate contraceptive methods. Male subjects have to agree to use contraception (condom with spermicide) in addition to having their female partner (if of childbearing potential) use another form of contraception (eg, an intrauterine device, diaphragm with spermicide, oral contraceptive, injectables, or subdermal hormonal implant) from the first dose until 4 months following the last dose administration. Also, the male subjects must not donate sperm until at least 4 months following the last dose administration.
- Evidence of acute or chronic infectious disease at Screening, including: positive Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus (HCV) antibody, or Human Immunodeficiency Virus (HIV) antibody.
- CYP2C19 poor metabolizers.
- Subjects who have used anticoagulants (ie, warfarin, low molecular weight heparin, thrombin inhibitors), antiplatelet (eg, clopidogrel), nonsteroidal anti-inflammatory drug, and/or aspirin within 30 days prior to Period 1, Day 1.
- Subjects with a history of major bleeding or major surgical procedure of any type within 6 months before Period 1, Day 1.
- Subjects with a history of peptic ulcer, gastrointestinal bleeding including haematemesis, melena, or bleeding from haemorrhoids.
- Subjects with a history of minor bleeding episodes such as epistaxis, rectal bleeding (spots of blood on toilet paper), or gingival bleeding within 3 months before Period 1, Day 1.
- Subjects who have any family history, suspected or documented, of coagulopathy or haemoglobinopathy or evidence of abnormal coagulation parameters (eg, PT, INR or aPTT) at Screening.
- Subjects with an estimated glomerular filtration rate (eGFR) at Screening using the Modification of Diet in Renal Disease (MDRD) equation < 90 mL/min.
- Likely possibility that the subject will not cooperate with the requirements of the protocol.
- Objection by General Practitioner to subjects entering the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-label, 2-period, Fixed-sequence Study to Evaluate the Safety and Tolerability of DS-1040b IV Infusion Coadministered With Clopidogrel in Healthy Subjects
This study is being conducted to test the hypothesis that coadministration of clopidogrel with DS-1040b will be safe and well tolerated. Subjects entering the study will initially receive a single 12 hour infusion of DS-1040b, to generate data on the effect of DS-1040b alone. After a wash-out period (to ensure that no DS-1040b is left in the blood) subjects will receive repeated clopidogrel doses over 5 days to generate data on the effect of clopidogrel alone. On the sixth day subjects will receive both DS-1040b and clopidogrel, and the effects will be compared to when the two treatments were given alone.
- Conditions
- Drug Interaction
- Being tested
- DS-1040b, Clopidogrel
- Keywords
- drug interaction, clopidogrel, healthy subjects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DS-1040bDrug
20 mg single 12-hour intravenous infusion
ClopidogrelDrug
Also called Plavix
Clopidogrel (Plavix) administered orally 300 mg loading dose on Day 1 followed by 75 mg daily on Days 2-5
| Study group | Role | What they receive |
|---|---|---|
| Period 1 - DS-1040b | Experimental | Single 12-hour intravenous infusion of DS-1040b (20 mg) Receives: Drug: DS-1040b |
| Period 2 - Clopidogrel | Other | Clopidogrel (Plavix) administered orally over 5 days (300 mg loading dose on Day 1 followed by 75 mg daily on Days 2-5) Receives: Drug: Clopidogrel |
| Period 2 - DS-1040b and Clopidogrel | Experimental | Concomitant administration of DS-1040b (20 mg single 12-hour intravenous infusion) and clopidogrel (single 75 mg oral dose) Receives: Drug: DS-1040b; Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of adverse events
Evaluation of the safety and tolerability of DS-1040 administered alone or with clopidogrel, as determined by adverse events,from the time of dosing up to 5 days postdose.
Measured: 5 days
physical exam profile
Evaluation of the safety and tolerability of DS-1040 administered alone or with clopidogrel, as determined by physical examination findings, vital signs, 12-lead electrocardiograms (ECGs), clinical safety laboratory tests from the time of dosing up to 5 days postdose.
Measured: 5 days
bleeding time measurements
Evaluation of the safety and tolerability of DS-1040 administered alone or with clopidogrel, as determined by bleeding time assessments from the time of dosing up to 5 days postdose.
Measured: 5 days
Secondary outcomes (8)
DS-1040b plasma concentration profile Time of Maximum plasma concentration(Tmax)
Plasma concentrations of DS-1040 and derived PK parameters up to 5 days after a single 20 mg intravenous infusion of DS-1040 (alone and with clopidogrel).
Measured: 5 days
DS-1040b plasma concentration profile Area Under the plasma concentration time Curve (AUC)
Plasma concentrations of DS-1040 and derived PK parameters up to 5 days after a single 20 mg intravenous infusion of DS-1040 (alone and with clopidogrel).
Measured: 5 days
DS-1040b plasma concentration profile Maximum plasma concentration (Cmax)
Plasma concentrations of DS-1040 and derived PK parameters up to 5 days after a single 20 mg intravenous infusion of DS-1040 (alone and with clopidogrel).
Measured: 5 days
changes in pharmacodynamic profile single administration
Change in baseline of pharmacodynamic parameters (thrombin activatable fibrinolysis inhibitor activity, clot lysis, plasma D-dimer, ADP-induced platelet aggregation) up to 5 days after a single 20 mg intravenous infusion of DS-1040 (alone and with clopidogrel).
Measured: 5 days
clopidogrel plasma concentration profile Tmax
Plasma concentrations of Clopidogrel Active Metabolite and derived PK parameters after repeated Clopidogrel administration (alone and with DS-1040)
Measured: 5 days
clopidogrel plasma concentration profile AUC
Plasma concentrations of Clopidogrel Active Metabolite and derived PK parameters after repeated Clopidogrel administration (alone and with DS-1040)
Measured: 5 days
clopidogrel plasma concentration profile Cmax
Plasma concentrations of Clopidogrel Active Metabolite and derived PK parameters after repeated Clopidogrel administration (alone and with DS-1040)
Measured: 5 days
changes in pharmacodynamic profile repeated administration
Change in baseline of pharmacodynamic parameters (thrombin activatable fibrinolysis inhibitor activity, clot lysis, plasma D-dimer, ADP-induced platelet aggregation) up to 5 days after repeated Clopidogrel administration (alone or with DS-1040)
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2015 (estimated)
- Study startDec 2015
- Primary completionMar 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Drug InteractionStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02560688
- Sponsor's protocol ID
- DS1040-A-E106
- Other IDs
- 2015-003018-26, 2015
- Status last verified
- Jun 2016
- First submitted
- 22 Sep 2015
- Last updated
- 24 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Publications
Limsakun T, Dishy V, Mendell J, Pizzagalli F, Pav J, Kochan J, Vandell AG, Rambaran C, Kobayashi F, Orihashi Y, Warren V, McPhillips P, Zhou J. Safety and Pharmacokinetics of DS-1040 Drug-Drug Interactions With Aspirin, Clopidogrel, and Enoxaparin. J Clin Pharmacol. 2020 Jun;60(6):691-701. doi: 10.1002/jcph.1568. Epub 2020 Feb 27.
PubMed 32106339
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, 2-period, Fixed-sequence Study to Evaluate the Safety and Tolerability of DS-1040b IV Infusion Coadministered With Clopidogrel in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02560688
- Acronym / sponsor ID
- DS1040-A-E106
- Conditions
- Drug Interaction
- Keywords
- drug interaction, clopidogrel, healthy subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- Dec 2015
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 25 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being conducted to test the hypothesis that coadministration of clopidogrel with DS-1040b will be safe and well tolerated. Subjects entering the study will initially receive a single 12 hour infusion of DS-1040b, to generate data on the effect of DS-1040b alone. After a wash-out period (to ensure that no DS-1040b is left in the blood) subjects will receive repeated clopidogrel doses over 5 days to generate data on the effect of clopidogrel alone. On the sixth day subjects will receive both DS-1040b and clopidogrel, and the effects will be compared to when the two treatments were given alone.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Period 1 - DS-1040b | Experimental | Drug: DS-1040bSingle 12-hour intravenous infusion of DS-1040b (20 mg) |
| Period 2 - Clopidogrel | Other | Drug: ClopidogrelClopidogrel (Plavix) administered orally over 5 days (300 mg loading dose on Day 1 followed by 75 mg daily on Days 2-5) |
| Period 2 - DS-1040b and Clopidogrel | Experimental | Drug: DS-1040b, Drug: ClopidogrelConcomitant administration of DS-1040b (20 mg single 12-hour intravenous infusion) and clopidogrel (single 75 mg oral dose) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Healthy male or female subjects of non-childbearing potential; subjects must be aged 18 years to 60 years, inclusive.
- Subjects with a body mass index (BMI) of 18 kg/m2 to 30 kg/m2, inclusive, and weighing between 50 kg and 100 kg, inclusive. BMI is calculated as weight [kg]/(height [m])*2.
- Subjects must be in good health as determined by medical history, physical examination and Screening investigations, and taking no regular medication.
- Female subjects must be of non-childbearing potential as follows:
- Willing to comply with all study restrictions, including the use of contraception, concomitant medication and dietary and lifestyle restrictions.
Key exclusion criteria (28 listed)
- Clinically relevant abnormal history, physical findings, ECG findings or laboratory values that could interfere with the objectives of the study or the safety of the subject.
- Presence or history of acute or chronic illness, including (but not limited to) liver or kidney disease, hypertension, seizures, or any known impairment of endocrine, or other specific body-organ dysfunction.
- Presence or history of severe adverse reaction to any medicine.
- Presence or history of malignant disease.
- Surgery (eg, stomach bypass) or medical condition that might affect absorption of medicines.
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 |
|---|---|---|
| DS-1040b20 mg single 12-hour intravenous infusion | Drug | Period 1 - DS-1040b, Period 2 - DS-1040b and Clopidogrel |
| ClopidogrelAlso: PlavixClopidogrel (Plavix) administered orally 300 mg loading dose on Day 1 followed by 75 mg daily on Days 2-5 | Drug | Period 2 - Clopidogrel, Period 2 - DS-1040b and Clopidogrel |
Primary outcome
number of adverse events
Time frame: 5 days
Evaluation of the safety and tolerability of DS-1040 administered alone or with clopidogrel, as determined by adverse events,from the time of dosing up to 5 days postdose.
physical exam profile
Time frame: 5 days
Evaluation of the safety and tolerability of DS-1040 administered alone or with clopidogrel, as determined by physical examination findings, vital signs, 12-lead electrocardiograms (ECGs), clinical safety laboratory tests from the time of dosing up to 5 days postdose.
bleeding time measurements
Time frame: 5 days
Evaluation of the safety and tolerability of DS-1040 administered alone or with clopidogrel, as determined by bleeding time assessments from the time of dosing up to 5 days postdose.
8 secondary outcomes
DS-1040b plasma concentration profile Time of Maximum plasma concentration(Tmax)
Time frame: 5 days
DS-1040b plasma concentration profile Area Under the plasma concentration time Curve (AUC)
Time frame: 5 days
DS-1040b plasma concentration profile Maximum plasma concentration (Cmax)
Time frame: 5 days
changes in pharmacodynamic profile single administration
Time frame: 5 days
clopidogrel plasma concentration profile Tmax
Time frame: 5 days
clopidogrel plasma concentration profile AUC
Time frame: 5 days
clopidogrel plasma concentration profile Cmax
Time frame: 5 days
changes in pharmacodynamic profile repeated administration
Time frame: 5 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2018.
- Derived from this study: PubMed 32106339Limsakun T, Dishy V, Mendell J, Pizzagalli F, Pav J, Kochan J, Vandell AG, Rambaran C, Kobayashi F, Orihashi Y, Warren V, McPhillips P, Zhou J. Safety and Pharmacokinetics of DS-1040 Drug-Drug Interactions With Aspirin, Clopidogrel, and Enoxaparin. J Clin Pharmacol. 2020 Jun;60(6):691-701. doi: 10.1002/jcph.1568. Epub 2020 Feb 27.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 DS-1040b and Clopidogrel in people with Drug Interaction, run by Daiichi Sankyo at 1 site in United Kingdom.
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 10 inclusion and 28 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 24 Dec 2018. 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 United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 adverse events (time frame: 5 days). The study lists 3 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 NCT02560688, 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 24 Dec 2018.