Torsades de PointesPhase 1TQTNCT00839891
A Study to Evaluate How VI-0521 Affect Cardiac Repolarization in Healthy Male and Female Volunteers
A Phase 1 study testing VI-0521 in people with Torsades de Pointes, run by VIVUS LLC at 1 site in United States.
Trial summary
Determine whether VI-0521 has an effect on the electrical activity of the heart in healthy subjects. Find out how much VI-0521 is in the blood and any potential side effects on ECG's of healthy subjects after taking the study drugs. Read more about this study
- Who is it for?
- Ages 19 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Torsades de Pointes
- What is being tested?
- VI-0521
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to Apr 2009
- 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 19 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males or females, aged 19 to 50 years, inclusive.
- Body mass index (BMI) between 24 and 30 kg/m2, inclusive.
- Subjects must be in good health, as determined by a medical history, physical examination, 12-lead ECG and clinical laboratory evaluations.
- Women of child-bearing potential should test negative for pregnancy, must use medically acceptable contraceptive methods
Who cannot join
- Male subjects with a resting QTcB or QTcF value <320 msec or >450 msec, and female subjects with a resting QTcB or QTcF value <320 msec or >470 msec, as measured at the screening visit.
- Subjects with clinically significant ECG abnormalities that may interfere with the accurate assessment of the QT interval, including intraventricular conduction delays (QRS >120 msec) and complete bundle branch blocks.
- Subjects who have a history of, or risk factors for, Torsades de Pointes (TdP) (eg, heart failure, abnormal serum electrolytes), including a family history of arrhythmia, sudden death or long QT syndrome.
- Subjects with known clinically significant arrhythmias or rhythm disturbances observed on the screening ECG and confirmed by a subsequent 24-hour ECG Holter recording.
- Subjects who have a supine heart rate (HR) at screening outside 45 to 90 beats per minute (bpm) (measured following at least a 10-minute rest).
- Subjects suffering from, or with a history of, one or more of the following conditions: hypertension, impaired glucose tolerance, diabetes mellitus, renal disease, edema, stroke or neurological disorder, rheumatological disorder (including arthritis, joint or tendon abnormalities), pulmonary disorder (including personal history of asthma), cardiovascular disorder (including coronary heart disease, congestive heart failure, cardiomyopathy, and any valvular heart disease), hepatic disorder, or a history of any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject by participation in the study.
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- Subjects with a history of psychiatric disorders, including bipolar disorder, psychosis, previous episode(s) of major depression or current depression, history of suicidality or suicidal ideation.
- Subjects with a history of nephrolithiasis or cholelithiasis.
- Subjects with a history of glaucoma, increased intraocular pressure, or use of any medication to treat increased intraocular pressure.
- Laboratory values at screening that are outside the normal range for the site unless prior approval is obtained from the VIVUS, Inc. medical monitor or designee.
- Subjects who are currently regular users (including recreational use) of any illicit drugs or who have a history of drug (including alcohol) abuse within 1 year of screening.
- Subjects who drink excessive amounts (equivalent to >4 cups of brewed coffee per day) of coffee, tea, cola or other caffeinated beverages within the 2 weeks prior to Day -1.
- Subjects with a positive urine drug test at screening and/or on Day -1 (eg, cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids).
- Subjects who consume excessive amounts of alcohol, defined as >3 drinks (beer, wine or distilled spirits) of alcoholic beverages per day, have a history of alcohol abuse, or are unwilling to comply with the restricted use of alcohol during the study.
- Subjects with a positive test for ethanol at screening and/or on Day -1.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel Group/Crossover Thorough QT/QTc Study to Evaluate the Effect of a Therapeutic Dose and a Supra-therapeutic Dose of VI-0521 on Cardiac Repolarization in Healthy Male and Female Volunteers
- Determine whether VI-0521 has an effect on the electrical activity of the heart in healthy subjects.
- Find out how much VI-0521 is in the blood and any potential side effects on ECG's of healthy subjects after taking the study drugs.
Read the detailed description
This three-arm, parallel group, double-blind, active- and placebo-controlled study comparing VI-0521 at a potential therapeutic dose of PHEN/TPM 7.5/46 and PHEN/TPM 22.5/138 , a supra-therapeutic dose, with placebo. A single oral dose of 400 mg moxifloxacin is included as a positive control in terms of the effect on cardiac repolarization. The three treatment regimens are defined as follows:
Group 1: 56 subjects to receive active study drug (VI-0521) at steady state, PHEN/TPM 7.5/46 (a potential therapeutic dose), escalating to PHEN/TPM 22.5/138 (a supra-therapeutic dose);
Group 2: 28 subjects to receive placebo preceded by a single oral dose of moxifloxacin on Day 2;
Group 3: 28 subjects to receive placebo followed by a single oral dose of moxifloxacin on Day 24;
A total of 112 healthy subjects (with an approximate 1:1 female:male ratio) are planned to be randomized.Subjects will check into the clinical research unit (CRU) on Day -1. Day 1 will be a baseline electrocardiogram (ECG) profile day (all groups). Active dosing for Group 1 with VI-0521 will commence on Day 2. VI-0521 dose will escalate every 2-3 days until steady-state is achieved on Day 10 for the therapeutic dose PHEN/TPM 7.5/46. A full ECG assessment day will be performed (all groups, blinded); enabling the comparison of VI 0521 PHEN/TPM 7.5/46 with the placebo (pooled Groups 2 and 3).Subsequently, VI-0521 doses will be escalated until subjects in Group 1 reach a dose of 22.5/138, and then continue at this dose level until Day 22. On Day 22, when the active group has reached a steady state for the supratherapeutic dose level, another ECG assessment day will be performed (all groups, blinded); enabling a comparison of supratherapeutic VI-0521 with placebo (pooled Groups 2 and 3). Groups 2 and 3 will receive VI-0521 placebo on Days 2 to 22.
- Conditions
- Torsades de Pointes
- Being tested
- VI-0521
- Keywords
- TQT, QTc
- Medical subject headings
- Torsades de Pointes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VI-0521Drug
PHEN/TPM 7.5/46 mg (a potential therapeutic dose) PHEN/TPM 22.5/138 mg (a supra-therapeutic dose)
| Study group | Role | What they receive |
|---|---|---|
| 3 | Placebo comparator | Group 1: 56 subjects to receive active study drug (VI-0521) at steady state, PHEN/TPM 7.5/46 (a potential therapeutic dose), escalating to PHEN/TPM 22.5/138 (a supra-therapeutic dose);
Group 2: 28 subjects to receive placebo preceded by a single oral dose of moxifloxacin on Day 2;
Group 3: 28 subjects to receive placebo followed by a single oral dose of moxifloxacin on Day 24; Receives: Drug: VI-0521 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective of this study is to assess whether treatment with a potential therapeutic dose or a supra-therapeutic dose of VI-0521 has the potential to cause QT/QTc prolongation in healthy volunteers.
Measured: 25 days
Secondary outcomes (1)
A secondary objective is to demonstrate assay sensitivity by showing that the active control (moxifloxacin 400 mg) treatment, corrected for placebo, produces a QTc change >5 msec.
Measured: 25 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2009 (estimated)
- Study startFeb 2009
- Primary completionApr 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Torsades de PointesStudies 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- VIVUS LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Shiyin Yee, PhD, Study director, Clinical Pharmacology Consultant
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00839891
- Sponsor's protocol ID
- OB-118
- Acronym
- TQT
- Status last verified
- Jan 2010
- First submitted
- 6 Feb 2009
- Last updated
- 21 Jan 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel Group/Crossover Thorough QT/QTc Study to Evaluate the Effect of a Therapeutic Dose and a Supra-therapeutic Dose of VI-0521 on Cardiac Repolarization in Healthy Male and Female Volunteers
- ClinicalTrials.gov ID
- NCT00839891
- Acronym / sponsor ID
- TQT / OB-118
- Conditions
- Torsades de Pointes
- Keywords
- TQT, QTc
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- VIVUS LLCIndustry (pharma, biotech, devices)
- Study start
- Feb 2009
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 10 Feb 2009 (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.
- Determine whether VI-0521 has an effect on the electrical activity of the heart in healthy subjects.
- Find out how much VI-0521 is in the blood and any potential side effects on ECG's of healthy subjects after taking the study drugs.
Detailed description
This three-arm, parallel group, double-blind, active- and placebo-controlled study comparing VI-0521 at a potential therapeutic dose of PHEN/TPM 7.5/46 and PHEN/TPM 22.5/138 , a supra-therapeutic dose, with placebo. A single oral dose of 400 mg moxifloxacin is included as a positive control in terms of the effect on cardiac repolarization. The three treatment regimens are defined as follows:
Group 1: 56 subjects to receive active study drug (VI-0521) at steady state, PHEN/TPM 7.5/46 (a potential therapeutic dose), escalating to PHEN/TPM 22.5/138 (a supra-therapeutic dose);
Group 2: 28 subjects to receive placebo preceded by a single oral dose of moxifloxacin on Day 2;
Group 3: 28 subjects to receive placebo followed by a single oral dose of moxifloxacin on Day 24;
A total of 112 healthy subjects (with an approximate 1:1 female:male ratio) are planned to be randomized.Subjects will check into the clinical research unit (CRU) on Day -1. Day 1 will be a baseline electrocardiogram (ECG) profile day (all groups). Active dosing for Group 1 with VI-0521 will commence on Day 2. VI-0521 dose will escalate every 2-3 days until steady-state is achieved on Day 10 for the therapeutic dose PHEN/TPM 7.5/46. A full ECG assessment day will be performed (all groups, blinded); enabling the comparison of VI 0521 PHEN/TPM 7.5/46 with the placebo (pooled Groups 2 and 3).Subsequently, VI-0521 doses will be escalated until subjects in Group 1 reach a dose of 22.5/138, and then continue at this dose level until Day 22. On Day 22, when the active group has reached a steady state for the supratherapeutic dose level, another ECG assessment day will be performed (all groups, blinded); enabling a comparison of supratherapeutic VI-0521 with placebo (pooled Groups 2 and 3). Groups 2 and 3 will receive VI-0521 placebo on Days 2 to 22.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 3 | Placebo comparator | Drug: VI-0521Group 1: 56 subjects to receive active study drug (VI-0521) at steady state, PHEN/TPM 7.5/46 (a potential therapeutic dose), escalating to PHEN/TPM 22.5/138 (a supra-therapeutic dose); Group 2: 28 subjects to receive placebo preceded by a single oral dose of moxifloxacin on Day 2; Group 3: 28 subjects to receive placebo followed by a single oral dose of moxifloxacin on Day 24; |
Who may qualify
- Ages
- 19 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Males or females, aged 19 to 50 years, inclusive.
- Body mass index (BMI) between 24 and 30 kg/m2, inclusive.
- Subjects must be in good health, as determined by a medical history, physical examination, 12-lead ECG and clinical laboratory evaluations.
- Women of child-bearing potential should test negative for pregnancy, must use medically acceptable contraceptive methods
Key exclusion criteria (15 listed)
- Male subjects with a resting QTcB or QTcF value <320 msec or >450 msec, and female subjects with a resting QTcB or QTcF value <320 msec or >470 msec, as measured at the screening visit.
- Subjects with clinically significant ECG abnormalities that may interfere with the accurate assessment of the QT interval, including intraventricular conduction delays (QRS >120 msec) and complete bundle branch blocks.
- Subjects who have a history of, or risk factors for, Torsades de Pointes (TdP) (eg, heart failure, abnormal serum electrolytes), including a family history of arrhythmia, sudden death or long QT syndrome.
- Subjects with known clinically significant arrhythmias or rhythm disturbances observed on the screening ECG and confirmed by a subsequent 24-hour ECG Holter recording.
- Subjects who have a supine heart rate (HR) at screening outside 45 to 90 beats per minute (bpm) (measured following at least a 10-minute rest).
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 |
|---|---|---|
| VI-0521PHEN/TPM 7.5/46 mg (a potential therapeutic dose) PHEN/TPM 22.5/138 mg (a supra-therapeutic dose) | Drug | 3 |
Primary outcome
The primary objective of this study is to assess whether treatment with a potential therapeutic dose or a supra-therapeutic dose of VI-0521 has the potential to cause QT/QTc prolongation in healthy volunteers.
Time frame: 25 days
1 secondary outcome
A secondary objective is to demonstrate assay sensitivity by showing that the active control (moxifloxacin 400 mg) treatment, corrected for placebo, produces a QTc change >5 msec.
Time frame: 25 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 21 Jan 2010.
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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.
Shiyin Yee, PhD study director
Clinical Pharmacology Consultant
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 VI-0521 in people with Torsades de Pointes, run by VIVUS 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 15 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 21 Jan 2010. 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?
The primary objective of this study is to assess whether treatment with a potential therapeutic dose or a supra-therapeutic dose of VI-0521 has the potential to cause QT/QTc prolongation in healthy volunteers. (time frame: 25 days). 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 21 Jan 2010.