HealthyPhase 1NCT01090661
A Study to Evaluate the Effect of Mipomersen on Cardiac Repolarization Conducted in Healthy Subjects
A Phase 1 study testing mipomersen sodium and moxifloxacin hydrochloride (Avelox®) in people with Healthy, run by Kastle Therapeutics, LLC at 1 site in United States.
Trial summary
To assess the electrocardiogram (ECG) effects of mipomersen administered as a 200-mg subcutaneous (SC) therapeutic and a 200-mg intravenous (IV; [2-hour infusion]) supra-therapeutic dose relative to placebo in healthy adult male and female subjects; and to evaluate the safety and pharmacokinetics (PK) of mipomersen… 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?
- mipomersen sodium and moxifloxacin hydrochloride (Avelox®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to May 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 provided before any study-related procedures are performed.
- Body mass index (BMI) of 19 to 32 kg/m2 inclusive.
- Subjects can not have consumed nicotine or nicotine-containing products for at least 6 months before Screening.
- Subjects are nonpregnant and nonlactating, surgically sterile, postmenopausal, abstinent, or subject or partner is willing to use a reliable method of contraception during the study and 5 months after the last dose of investigational product.
Who cannot join
- History of risk factors for Torsades de Pointes, known Long QT Syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments or family history of Long QT or Brugada Syndrome.
- Abnormal screening ECG that is interpreted by the Investigator to be clinically significant.
- Use of concomitant medications (prescribed or over-the-counter), without the approval of the Investigator and Sponsor, within 7 days before the first dose of investigational product.
- Clinically significant abnormal findings on the physical examination, ECG, blood pressure, heart rate, medical history, or clinical laboratory results at Screening or before dosing.
- History of clinically significant allergies or hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease.
- Positive test for HIV antibody, hepatitis C antibody, or hepatitis B surface antigen.
- Positive test for drugs of abuse, alcohol, or cotinine at Screening or before dosing or history of drug or alcohol abuse or dependence within 1 year before Screening.
- History of cancer, with the exception of basal cell carcinoma.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Double-Blinded Crossover Trial to Define the ECG Effects of Mipomersen (ISIS 301012) Using a Therapeutic and Supratherapeutic Dose Compared to Placebo and Moxifloxacin (a Positive Control) in Healthy Men and Women: A Thorough ECG Trial
To assess the electrocardiogram (ECG) effects of mipomersen administered as a 200-mg subcutaneous (SC) therapeutic and a 200-mg intravenous (IV; [2-hour infusion]) supra-therapeutic dose relative to placebo in healthy adult male and female subjects; and to evaluate the safety and pharmacokinetics (PK) of mipomersen when administered as a single therapeutic (200 mg) SC and a single, supra-therapeutic (200 mg) IV dose.
Read the detailed description
This will be a randomized, double-blind, single-site, crossover study in healthy male and female subjects to determine if mipomersen administered as a single therapeutic (200 mg) SC and a single supra-therapeutic (200 mg) IV dose delays cardiac repolarization as determined by the measurement of QT/corrected QT (QTc) interval. A total of 60 healthy male and female subjects will be enrolled in this 4-way crossover study, randomly assigned to 1 of 8 treatment sequences, and cross over into 4 treatment periods where each subject will receive both a single SC injection and a single IV infusion during each period.
- Conditions
- Healthy
- Being tested
- mipomersen sodium, moxifloxacin hydrochloride (Avelox®), placebo
- Keywords
- antisense, ApoB (Apolipoprotein B), LDL (low density lipoprotein), thorough QT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mipomersen sodiumDrug
Also called ISIS 301012
200 mg of mipomersen intravenous (IV) (single dose)
mipomersen sodiumDrug
Also called ISIS 301012
200 mg of mipomersen subcutaneous (SC) (single dose)
moxifloxacin hydrochloride (Avelox®)Drug
400 mg of moxifloxacin intravenous (IV) single dose
placeboDrug
placebo intravenous (IV) single dose
placeboDrug
placebo subcutaneous (SC) single dose
| Study group | Role | What they receive |
|---|---|---|
| mipomersen IV (supra-therapeutic dose) | Experimental | 200 mg of mipomersen IV / placebo SC Receives: Drug: mipomersen sodium; Drug: placebo |
| mipomersen SC (therapeutic dose) | Experimental | 200 mg of mipomersen SC / placebo IV Receives: Drug: mipomersen sodium; Drug: placebo |
| moxifloxacin IV | Active comparator | 400 mg of moxifloxacin IV / placebo SC Receives: Drug: moxifloxacin hydrochloride (Avelox®); Drug: placebo |
| placebo | Placebo comparator | Placebo IV / placebo SC Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
change from baseline in QTcF (corrected Frederica's CT interval)
Measured: ECG monitoring up to 24 hours post dose
Secondary outcomes (5)
ECG intervals (QTcB (corrected Bazett's QT interval), HR (heart rate, PR, QRS, and QT)
Measured: ECG monitoring up to 24 hours post dose
change in ECG morphological patterns
Measured: ECG monitoring up to 24 hours post dose
Correlation between delta delta QTc interval and plasma mipomersen concentrations
Measured: ECG monitoring up to 24 hours post dose
Incidence of treatment-emergent Adverse Events
Measured: Assessed at each visit
mipomersen plasma pharmacokinetic (PK) parameters: Area Under the Curve (AUC 0-22.5h), Maximum Concentration (Cmax), Time to Maximum Concentration (Tmax)
Measured: Serial PK sampling up to 24 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionMay 2010
- Study completionMay 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
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 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
- NCT01090661
- Sponsor's protocol ID
- MIPO2800209
- Status last verified
- Aug 2016
- First submitted
- 18 Mar 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 Randomized Double-Blinded Crossover Trial to Define the ECG Effects of Mipomersen (ISIS 301012) Using a Therapeutic and Supratherapeutic Dose Compared to Placebo and Moxifloxacin (a Positive Control) in Healthy Men and Women: A Thorough ECG Trial
- ClinicalTrials.gov ID
- NCT01090661
- Acronym / sponsor ID
- MIPO2800209
- Conditions
- Healthy
- Keywords
- antisense, ApoB (Apolipoprotein B), LDL (low density lipoprotein), thorough QT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Kastle Therapeutics, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Study start
- Mar 2010
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 22 Mar 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.
To assess the electrocardiogram (ECG) effects of mipomersen administered as a 200-mg subcutaneous (SC) therapeutic and a 200-mg intravenous (IV; [2-hour infusion]) supra-therapeutic dose relative to placebo in healthy adult male and female subjects; and to evaluate the safety and pharmacokinetics (PK) of mipomersen when administered as a single therapeutic (200 mg) SC and a single, supra-therapeutic (200 mg) IV dose.
Detailed description
This will be a randomized, double-blind, single-site, crossover study in healthy male and female subjects to determine if mipomersen administered as a single therapeutic (200 mg) SC and a single supra-therapeutic (200 mg) IV dose delays cardiac repolarization as determined by the measurement of QT/corrected QT (QTc) interval. A total of 60 healthy male and female subjects will be enrolled in this 4-way crossover study, randomly assigned to 1 of 8 treatment sequences, and cross over into 4 treatment periods where each subject will receive both a single SC injection and a single IV infusion during each period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| mipomersen IV (supra-therapeutic dose) | Experimental | Drug: mipomersen sodium, Drug: placebo200 mg of mipomersen IV / placebo SC |
| mipomersen SC (therapeutic dose) | Experimental | Drug: mipomersen sodium, Drug: placebo200 mg of mipomersen SC / placebo IV |
| moxifloxacin IV | Active comparator | Drug: moxifloxacin hydrochloride (Avelox®), Drug: placebo400 mg of moxifloxacin IV / placebo SC |
| placebo | Placebo comparator | Drug: placeboPlacebo IV / placebo SC |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Written informed consent provided before any study-related procedures are performed.
- Body mass index (BMI) of 19 to 32 kg/m2 inclusive.
- Subjects can not have consumed nicotine or nicotine-containing products for at least 6 months before Screening.
- Subjects are nonpregnant and nonlactating, surgically sterile, postmenopausal, abstinent, or subject or partner is willing to use a reliable method of contraception during the study and 5 months after the last dose of investigational product.
Key exclusion criteria (8 listed)
- History of risk factors for Torsades de Pointes, known Long QT Syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments or family history of Long QT or Brugada Syndrome.
- Abnormal screening ECG that is interpreted by the Investigator to be clinically significant.
- Use of concomitant medications (prescribed or over-the-counter), without the approval of the Investigator and Sponsor, within 7 days before the first dose of investigational product.
- Clinically significant abnormal findings on the physical examination, ECG, blood pressure, heart rate, medical history, or clinical laboratory results at Screening or before dosing.
- History of clinically significant allergies or hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease.
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 |
|---|---|---|
| mipomersen sodiumAlso: ISIS 301012200 mg of mipomersen intravenous (IV) (single dose) | Drug | mipomersen IV (supra-therapeutic dose) |
| mipomersen sodiumAlso: ISIS 301012200 mg of mipomersen subcutaneous (SC) (single dose) | Drug | mipomersen SC (therapeutic dose) |
| moxifloxacin hydrochloride (Avelox®)400 mg of moxifloxacin intravenous (IV) single dose | Drug | moxifloxacin IV |
| placeboplacebo intravenous (IV) single dose | Drug | mipomersen SC (therapeutic dose), placebo |
| placeboplacebo subcutaneous (SC) single dose | Drug | mipomersen IV (supra-therapeutic dose), moxifloxacin IV, placebo |
Primary outcome
change from baseline in QTcF (corrected Frederica's CT interval)
Time frame: ECG monitoring up to 24 hours post dose
5 secondary outcomes
ECG intervals (QTcB (corrected Bazett's QT interval), HR (heart rate, PR, QRS, and QT)
Time frame: ECG monitoring up to 24 hours post dose
change in ECG morphological patterns
Time frame: ECG monitoring up to 24 hours post dose
Correlation between delta delta QTc interval and plasma mipomersen concentrations
Time frame: ECG monitoring up to 24 hours post dose
Incidence of treatment-emergent Adverse Events
Time frame: Assessed at each visit
mipomersen plasma pharmacokinetic (PK) parameters: Area Under the Curve (AUC 0-22.5h), Maximum Concentration (Cmax), Time to Maximum Concentration (Tmax)
Time frame: Serial PK sampling up to 24 hours post dose
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 mipomersen sodium and moxifloxacin hydrochloride (Avelox®) 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 4 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. 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?
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?
change from baseline in QTcF (corrected Frederica's CT interval) (time frame: ECG monitoring up to 24 hours post dose). 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.