HealthyPhase 1NCT01133366
A Study to Determine the Effects of Multiple Doses of Mipomersen (200 mg SC) on the Pharmacodynamics and Pharmacokinetics of Single-dose Warfarin
A Phase 1 study testing warfarin sodium and mipomersen sodium; warfarin sodium in people with Healthy, run by Kastle Therapeutics, LLC at 1 site in United States.
Trial summary
The purpose of this study is to assess how blood clotting and thinning time is effected when a single dose of warfarin is given alone and when a single dose of warfarin is given with mipomersen; to assess the blood levels of a single dose of warfarin, a single dose of mipomersen, and a single dose of warfarin when… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- warfarin sodium and mipomersen sodium; warfarin sodium
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to Jul 2010
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written informed consent before any study-related procedure is performed.
- Body mass index (BMI) between 18 and 32 kg/m2, inclusive.
- No clinically significant abnormalities based on medical history, laboratory assessments, vital sign, 12-lead electrocardiogram (ECG) results, and physical examination.
- Subjects willing and able to follow a prescribed diet.
- Subjects have not consumed nicotine or nicotine-containing products for at least 6 months before Screening.
- Subjects are nonpregnant and nonlactating, surgically sterile, postmenopausal, abstinent, or the subject or partner is willing to use a reliable method of contraception during the study and for 5 months after mipomersen dosing.
Who cannot join
- Poor metabolizer of warfarin as determined by CYP2C9 genotype testing.
- Clinically significant PT, aPTT, INR, protein C, protein S, or platelet count results or hematuria.
- Abnormal prolongation of skin bleeding time or a personal or family history of coagulation or bleeding disorders, vascular malformations including aneurysms, or venous thromboembolism.
- Active or recurring clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal, or metabolic disease.
- Active malignancy of any type other than nonmelanomatous skin malignancies.
- Use of any prescribed or over-the-counter concomitant medications within 14 days before the first dose of investigational product without approval of the Investigator and Sponsor.
- Positive test result for drugs of abuse, alcohol, or cotinine or history of alcohol abuse or drug addiction.
- Positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or HIV.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Drug-Drug Interaction Study to Assess the Effects of Multiple Doses of Mipomersen (200 mg SC) on Single-Dose Warfarin (25 mg) Pharmacodynamics and Pharmacokinetics in Healthy Adult Subjects
The purpose of this study is to assess how blood clotting and thinning time is effected when a single dose of warfarin is given alone and when a single dose of warfarin is given with mipomersen; to assess the blood levels of a single dose of warfarin, a single dose of mipomersen, and a single dose of warfarin when given with mipomersen; and to assess the safety of mipomersen when given with or without warfarin.
Read the detailed description
This will be a Phase 1, open-label, single-sequence, 2-period, crossover study to determine the effect of multiple doses of mipomersen (200 mg SC given every other day for a total of 4 doses) on the PD and PK of warfarin and to evaluate the PK of mipomersen when administered alone and in combination with warfarin. Subjects will be admitted to the clinic on Day -1 until discharge from the clinic on Day 18 and return for outpatient visits on Days 19, 20, and 78. All subjects will receive a single 25-mg oral dose of warfarin given alone on Day 1 (designated the reference treatment). All subjects will then receive 200-mg SC doses of mipomersen given every other day on Days 8, 10, 12, and 14 (total of 800 mg mipomersen) with a single 25-mg oral dose of warfarin also given on Day 14 (combination designated the test treatment).
- Conditions
- Healthy
- Being tested
- warfarin sodium, mipomersen sodium; warfarin sodium
- Keywords
- ISIS301012, antisense, ApoB (Apolipoprotein B), LDL (low density lipoprotein), mipomersen
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
warfarin sodiumDrug
Also called Coumadin®
25 mg of warfarin oral (single dose)
mipomersen sodium; warfarin sodiumDrug
Also called Coumadin®
200 mg of mipomersen subcutaneous (SC) (4 doses) plus a single 25 mg of warfarin oral administered with the final mipomersen SC dose
| Study group | Role | What they receive |
|---|---|---|
| warfarin alone | Active comparator | Not described Receives: Drug: warfarin sodium |
| warfarin with mipomersen | Experimental | Not described Receives: Drug: mipomersen sodium; warfarin sodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the effect curve (AUC), for INR (international normalized ratio), PT (prothrombin time), and aPTT (activated partial thromboplastin time)
Measured: Serial sampling up to 144 hours post dose
Maximal Value (MAX) for INR, PT and aPTT
Measured: Serial sampling up to 144 hours post dose
Time of maximal effect (Tmax) for INR, PT, and aPTT
Measured: Serial sampling up to 144 hours post dose
Secondary outcomes (3)
Warfarin Plasma Pharmacokinetic parameters (AUC 0-t, AUC 0-inf, Maximum Concentration (Cmax))
Measured: Serial PK sampling up to 144 hours post dose
Mipomersen Plasma Pharmacokinetic parameters (AUC0-t, AUC0-inf, Cmax)
Measured: Serial PK sampling up to 24 hours post dose
Incidence of treatment-emergent Adverse Events
Measured: Through Day 78
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2010 (estimated)
- Study startMay 2010
- Primary completionMay 2010
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kastle Therapeutics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01133366
- Sponsor's protocol ID
- MIPO2900509
- Status last verified
- Aug 2016
- First submitted
- 27 May 2010
- Last updated
- 3 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Drug-Drug Interaction Study to Assess the Effects of Multiple Doses of Mipomersen (200 mg SC) on Single-Dose Warfarin (25 mg) Pharmacodynamics and Pharmacokinetics in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT01133366
- Acronym / sponsor ID
- MIPO2900509
- Conditions
- Healthy
- Keywords
- ISIS301012, antisense, ApoB (Apolipoprotein B), LDL (low density lipoprotein), mipomersen
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Kastle Therapeutics, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Study start
- May 2010
- Primary completion
- May 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 28 May 2010 (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.
The purpose of this study is to assess how blood clotting and thinning time is effected when a single dose of warfarin is given alone and when a single dose of warfarin is given with mipomersen; to assess the blood levels of a single dose of warfarin, a single dose of mipomersen, and a single dose of warfarin when given with mipomersen; and to assess the safety of mipomersen when given with or without warfarin.
Detailed description
This will be a Phase 1, open-label, single-sequence, 2-period, crossover study to determine the effect of multiple doses of mipomersen (200 mg SC given every other day for a total of 4 doses) on the PD and PK of warfarin and to evaluate the PK of mipomersen when administered alone and in combination with warfarin. Subjects will be admitted to the clinic on Day -1 until discharge from the clinic on Day 18 and return for outpatient visits on Days 19, 20, and 78. All subjects will receive a single 25-mg oral dose of warfarin given alone on Day 1 (designated the reference treatment). All subjects will then receive 200-mg SC doses of mipomersen given every other day on Days 8, 10, 12, and 14 (total of 800 mg mipomersen) with a single 25-mg oral dose of warfarin also given on Day 14 (combination designated the test treatment).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| warfarin alone | Active comparator | Drug: warfarin sodium |
| warfarin with mipomersen | Experimental | Drug: mipomersen sodium; warfarin sodium |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Written informed consent before any study-related procedure is performed.
- Body mass index (BMI) between 18 and 32 kg/m2, inclusive.
- No clinically significant abnormalities based on medical history, laboratory assessments, vital sign, 12-lead electrocardiogram (ECG) results, and physical examination.
- Subjects willing and able to follow a prescribed diet.
- Subjects have not consumed nicotine or nicotine-containing products for at least 6 months before Screening.
Key exclusion criteria (8 listed)
- Poor metabolizer of warfarin as determined by CYP2C9 genotype testing.
- Clinically significant PT, aPTT, INR, protein C, protein S, or platelet count results or hematuria.
- Abnormal prolongation of skin bleeding time or a personal or family history of coagulation or bleeding disorders, vascular malformations including aneurysms, or venous thromboembolism.
- Active or recurring clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal, or metabolic disease.
- Active malignancy of any type other than nonmelanomatous skin malignancies.
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 |
|---|---|---|
| warfarin sodiumAlso: Coumadin®25 mg of warfarin oral (single dose) | Drug | warfarin alone |
| mipomersen sodium; warfarin sodiumAlso: Coumadin®200 mg of mipomersen subcutaneous (SC) (4 doses) plus a single 25 mg of warfarin oral administered with the final mipomersen SC dose | Drug | warfarin with mipomersen |
Primary outcome
Area under the effect curve (AUC), for INR (international normalized ratio), PT (prothrombin time), and aPTT (activated partial thromboplastin time)
Time frame: Serial sampling up to 144 hours post dose
Maximal Value (MAX) for INR, PT and aPTT
Time frame: Serial sampling up to 144 hours post dose
Time of maximal effect (Tmax) for INR, PT, and aPTT
Time frame: Serial sampling up to 144 hours post dose
3 secondary outcomes
Warfarin Plasma Pharmacokinetic parameters (AUC 0-t, AUC 0-inf, Maximum Concentration (Cmax))
Time frame: Serial PK sampling up to 144 hours post dose
Mipomersen Plasma Pharmacokinetic parameters (AUC0-t, AUC0-inf, Cmax)
Time frame: Serial PK sampling up to 24 hours post dose
Incidence of treatment-emergent Adverse Events
Time frame: Through Day 78
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 3 Aug 2016.
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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.
Medical Monitor study director
Genzyme, a Sanofi Company
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 warfarin sodium and mipomersen sodium; warfarin sodium in people with Healthy, run by Kastle Therapeutics, LLC at 1 site in United States.
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 6 inclusion and 8 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 3 Aug 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 United States. 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?
Area under the effect curve (AUC), for INR (international normalized ratio), PT (prothrombin time), and aPTT (activated partial thromboplastin time) (time frame: Serial sampling up to 144 hours post dose). 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?
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 3 Aug 2016; AzTrials last refreshed its copy on 1 Nov 2026.