QTc IntervalPhase 1NCT01327066
Electrocardiographic (ECG) Safety Study of Droxidopa at Clinical and Supratherapeutic Dose
A Phase 1 study testing Droxidopa and Moxifloxacin in people with QTc Interval, run by Chelsea Therapeutics at 1 site in United States.
Trial summary
The purpose of this study is define the electrocardiographic (ECG) effects of Droxidopa at clinical (600 mg) and supratherapeutic (2000 mg) doses compared with placebo and moxifloxacin in healthy male and female subjects. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- QTc Interval
- What is being tested?
- Droxidopa and Moxifloxacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Jun 2011
- 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
- Male or female subject in good general health and 18 to 45 years of age, inclusive.
- Female subjects must be nonpregnant, nonlactating, and have a negative serum pregnancy test before enrollment in the study. Female subjects of childbearing potential (including perimenopausal women who have had menstrual bleeding within 1 year) must be using appropriate birth control (abstinence and/or barrier methods and/or oral, injectable, or implantable hormonal contraceptives) during the entire duration of the study. Women are considered of non-childbearing potential if they are menopausal (last menstrual period greater than 12 months before Check in and a serum follicle stimulating hormone level greater than 40 mIU/mL) or have been surgically sterilized (documented hysterectomy, tubal ligation, or bilateral oophorectomy) at least 6 weeks before Check in.
- Subject has a body mass index of 18.0 to 30.0 kg/m2, inclusive.
- Subject provides written informed consent.
- Subject is willing and able to comply with all study requirements.
- Subject has no clinically significant abnormal medical history, clinical laboratory results, vital sign measurements, 12 lead safety ECG results, or physical examination findings during Screening.
Who cannot join
- Subject is currently participating in another clinical study of an investigational drug (or a medical device), or has participated in a study of this type within 30 days before Check in.
- Subject has a history or current evidence of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at the time of dosing or mild allergic reactions to drugs other than those listed in exclusion criterion #16), hematologic, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurologic disease. Exceptions to these criteria (eg, stable mild joint disease, cholecystectomy, or childhood asthma) may be made after discussion with the medical monitor.
- Subject has used any prescribed or over the counter medication without the approval of the investigator or sponsor within 1 week before the first dose of study drug (including dietary supplements, herbal remedies, and medications known to prolong the QT/corrected QT [QTc] interval).
- Subject is receiving any anticoagulant (eg, coumadin, heparin, low molecular weight heparin) or has received any anticoagulant within 3 months before Check in. Subjects who are receiving any drugs that affect platelet function (eg, aspirin, including low-dose aspirin) will also be excluded.
- Subject has a history of drug or alcohol abuse or dependence within 1 year before Check in.
- Subject has donated blood or blood components within 4 weeks before Check in. The investigator should instruct subjects who participate in this study not to donate blood or blood components for 4 weeks after completion of the study.
Show all 17Show fewer
- Subject has a sustained supine systolic blood pressure > 140 mm Hg or < 90 mm Hg or a supine diastolic blood pressure > 95 mm Hg or < 50 mm Hg at Screening or Check in. Blood pressure may be retested once in the supine position. The blood pressure abnormality is considered sustained if either the systolic or the diastolic pressure values are outside the stated limits after 2 assessments, and the subject may not be randomized.
- Subject has a resting heart rate (HR) of < 45 beats per minute or > 100 beats per minute when vital signs are measured at Screening or Check in.
- Subject has an abnormal screening ECG indicating a second or third degree atrioventricular block, or one or more of the following: QRS interval > 110 milliseconds (ms); QT interval corrected for HR by Fridericia's formula (QTcF) > 450 ms; PR interval > 200 ms; or any rhythm other than sinus rhythm that is interpreted by the investigator to be clinically significant.
- Subject has a history of risk factors for torsades de pointes, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or hypomagnesemia. Subjects will also be excluded if there is a family history of long QT syndrome or Brugada syndrome.
- Subject uses or has used nicotine-containing products (eg, cigarettes, cigars, chewing tobacco, snuff) within 2 weeks before Check in, or subject has a positive cotinine result (indicating active current smoking) at Screening or Check in.
- Subject has consumed alcohol or xanthine-containing products (eg, tea, coffee, chocolate, cola) within 72 hours before Check in, or subject has a positive result for drug(s) of abuse or ethanol at Screening or Check in.
- Subject consumes ≥ 500 mg per day of caffeine (eg, 5 cups of tea or coffee; 8 cans or five 20 ounce bottles of cola).
- Subject has been treated with any investigational agent within 30 days before Check in (or 5 half-lives of the compound, if longer).
- Subject who, for any reason, is deemed by the investigator to be inappropriate for this study, including a subject who is unable to communicate or cooperate with the investigator.
- Subject has known allergies to droxidopa, moxifloxacin, any excipient in the study drug(s), or encapsulation formulations (subject will not be excluded for mild allergic reactions to drugs other than those listed in this criterion).
- Subject has received treatment with droxidopa within 30 days before Check in.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-Blind Randomized Crossover Trial to Define the Ecg Effects of Droxidopa Using a Clinical and a Supratherapeutic Dose Compared With Placebo and Moxifloxacin (a Positive Control) in Healthy Men and Women: a Thorough ECG Trial
The purpose of this study is define the electrocardiographic (ECG) effects of Droxidopa at clinical (600 mg) and supratherapeutic (2000 mg) doses compared with placebo and moxifloxacin in healthy male and female subjects.
Read the detailed description
This will be a randomized, double blind, single-site, 4 period crossover study in healthy male and female subjects to determine if droxidopa administered as a single therapeutic (600 mg) and a single supratherapeutic (2000 mg) dose delays cardiac repolarization as determined by the measurement of QTc interval. Study drug (droxidopa, placebo, and moxifloxacin) will be administered in a double blind, double dummy manner. The central ECG laboratory (eResearch Technology, Inc, Philadelphia, Pennsylvania) will be blinded to treatment.
A total of 52 healthy subjects (approximately 26 women and 26 men) will be enrolled and randomly assigned to a treatment sequence. Subjects will cross over into 4 treatment periods where each subject will receive single doses of the following treatments under fasting conditions separated by a minimum 3 day washout period (from Day 1):
- Droxidopa 600 mg (therapeutic dose), oral capsules
- Droxidopa 2000 mg (supratherapeutic dose), oral capsules
- Placebo (matched to droxidopa), oral capsules
- Moxifloxacin 400 mg (positive control; over encapsulated), oral Subjects will be screened for study participation from Days -21 to -2 and admitted to the clinic on Day -2 of Period 1 for prestudy assessments. On Day -1 of each period, subjects will undergo a full day of continuous 12 lead Holter monitoring; 4 ECGs will be extracted from the H 12+ flash card approximately 1 minute apart at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, and 23 hours.
On the morning of Day 1 of each period, after at least an 8 hour fast, subjects will receive a single dose of study drug according to the randomly assigned treatment sequence. After dosing, subjects will be monitored for 23 hours using a continuous 12 lead ECG Holter monitor. At the ECG core laboratory, 4 ECGs will be extracted approximately 1 minute apart at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, and 23 hours (Day 2) after dosing. The ECGs will be extracted from Holter recording flashcards during a 10 minute ECG extraction window that will end at the onset of each pharmacokinetic (PK) collection nominal time point. Each ECG extraction window will be preceded by a 10 minute supine rest period.
A single 12 lead ECG will be performed at Screening for inclusion/exclusion in the study, and a baseline safety 12 lead ECG will be performed at Check in. In addition, a safety 12 lead ECG will be recorded and reviewed by the investigator on Day 1 of each period at 2 hours after dosing.
Pharmacokinetic blood samples will be collected on Day 1 of each period before dosing and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, and 23 hours (Day 2) after dosing. Subjects will be supine for at least 10 minutes before each of the time points for PK samples. The ECG extractions will be time matched to the PK samples, but will be obtained before the actual sampling time to avoid changes in autonomic tone associated with the psychological aspects of blood collection as well as the reduction in blood volume subsequent to blood collection.
Meal timing and components, activity levels, and general conditions in the Phase I unit will be as similar as possible on Day -1 and Day 1 of each treatment period. Subjects will be discharged on Day 2 of Period 4 (ie, 24 hours after the last dose is administered). The total study duration will be approximately 34 days.
- Conditions
- QTc Interval
- Being tested
- Droxidopa, Moxifloxacin, Placebo
- Keywords
- QTc, ECG Effects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DroxidopaDrug
Also called L-DOPS, Northera
600 mg, single oral dose
DroxidopaDrug
Also called L-DOPS, Northera
2000 mg, single oral dose
MoxifloxacinDrug
Also called Avelox
400 mg, single oral dose
PlaceboDrug
Also called sugar pill, sham
Placebo matching Droxidopa or Moxifloxacin
| Study group | Role | What they receive |
|---|---|---|
| Droxidopa - Therapeutic | Experimental | Droxidopa 600 mg Receives: Drug: Droxidopa |
| Droxidopa - Supratherapeutic Dose | Experimental | Droxidopa 2000 mg Receives: Drug: Droxidopa |
| Placebo | Placebo comparator | Placebo Receives: Drug: Moxifloxacin; Drug: Placebo |
| Moxifloxacin | Active comparator | Moxifloxacin 400 mg dose Receives: Drug: Moxifloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
ECG Effects
The primary ECG endpoint is the time matched, placebo adjusted change from Baseline in QT interval corrected using an individual correction method (QTcI) (ΔΔQTcI). The QTcI method provides an optimization of QT correction for HR as compared with fixed exponent approaches such as Bazett (QTcB) or Fridericia (QTcF).
Measured: Baseline to End of Treatment (12 days)
Secondary outcomes (1)
QTcF and QTcB (for historic reasons only), HR, and PR, QRS, and uncorrected QT intervals, change in ECG morphological patterns, and the correlation between the QTcI change and droxidopa plasma concentrations
Measured: Baseline to End of Treatment (12 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2011 (estimated)
- Study startMar 2011
- Primary completionApr 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for QTc IntervalStudies 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
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chelsea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Thomas Hunt, MD, Principal investigator, PPD Phase I Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01327066
- Sponsor's protocol ID
- Droxidopa QTc102
- Status last verified
- Mar 2012
- First submitted
- 30 Mar 2011
- Last updated
- 7 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind Randomized Crossover Trial to Define the Ecg Effects of Droxidopa Using a Clinical and a Supratherapeutic Dose Compared With Placebo and Moxifloxacin (a Positive Control) in Healthy Men and Women: a Thorough ECG Trial
- ClinicalTrials.gov ID
- NCT01327066
- Acronym / sponsor ID
- Droxidopa QTc102
- Conditions
- QTc Interval
- Keywords
- QTc, ECG Effects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Chelsea TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Mar 2011
- Primary completion
- Apr 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 1 Apr 2011 (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 define the electrocardiographic (ECG) effects of Droxidopa at clinical (600 mg) and supratherapeutic (2000 mg) doses compared with placebo and moxifloxacin in healthy male and female subjects.
Detailed description
This will be a randomized, double blind, single-site, 4 period crossover study in healthy male and female subjects to determine if droxidopa administered as a single therapeutic (600 mg) and a single supratherapeutic (2000 mg) dose delays cardiac repolarization as determined by the measurement of QTc interval. Study drug (droxidopa, placebo, and moxifloxacin) will be administered in a double blind, double dummy manner. The central ECG laboratory (eResearch Technology, Inc, Philadelphia, Pennsylvania) will be blinded to treatment.
A total of 52 healthy subjects (approximately 26 women and 26 men) will be enrolled and randomly assigned to a treatment sequence. Subjects will cross over into 4 treatment periods where each subject will receive single doses of the following treatments under fasting conditions separated by a minimum 3 day washout period (from Day 1):
- Droxidopa 600 mg (therapeutic dose), oral capsules
- Droxidopa 2000 mg (supratherapeutic dose), oral capsules
- Placebo (matched to droxidopa), oral capsules
- Moxifloxacin 400 mg (positive control; over encapsulated), oral Subjects will be screened for study participation from Days -21 to -2 and admitted to the clinic on Day -2 of Period 1 for prestudy assessments. On Day -1 of each period, subjects will undergo a full day of continuous 12 lead Holter monitoring; 4 ECGs will be extracted from the H 12+ flash card approximately 1 minute apart at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, and 23 hours.
On the morning of Day 1 of each period, after at least an 8 hour fast, subjects will receive a single dose of study drug according to the randomly assigned treatment sequence. After dosing, subjects will be monitored for 23 hours using a continuous 12 lead ECG Holter monitor. At the ECG core laboratory, 4 ECGs will be extracted approximately 1 minute apart at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, and 23 hours (Day 2) after dosing. The ECGs will be extracted from Holter recording flashcards during a 10 minute ECG extraction window that will end at the onset of each pharmacokinetic (PK) collection nominal time point. Each ECG extraction window will be preceded by a 10 minute supine rest period.
A single 12 lead ECG will be performed at Screening for inclusion/exclusion in the study, and a baseline safety 12 lead ECG will be performed at Check in. In addition, a safety 12 lead ECG will be recorded and reviewed by the investigator on Day 1 of each period at 2 hours after dosing.
Pharmacokinetic blood samples will be collected on Day 1 of each period before dosing and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, and 23 hours (Day 2) after dosing. Subjects will be supine for at least 10 minutes before each of the time points for PK samples. The ECG extractions will be time matched to the PK samples, but will be obtained before the actual sampling time to avoid changes in autonomic tone associated with the psychological aspects of blood collection as well as the reduction in blood volume subsequent to blood collection.
Meal timing and components, activity levels, and general conditions in the Phase I unit will be as similar as possible on Day -1 and Day 1 of each treatment period. Subjects will be discharged on Day 2 of Period 4 (ie, 24 hours after the last dose is administered). The total study duration will be approximately 34 days.
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 |
|---|---|---|
| Droxidopa - Therapeutic | Experimental | Drug: DroxidopaDroxidopa 600 mg |
| Droxidopa - Supratherapeutic Dose | Experimental | Drug: DroxidopaDroxidopa 2000 mg |
| Placebo | Placebo comparator | Drug: Moxifloxacin, Drug: PlaceboPlacebo |
| Moxifloxacin | Active comparator | Drug: MoxifloxacinMoxifloxacin 400 mg dose |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Male or female subject in good general health and 18 to 45 years of age, inclusive.
- Female subjects must be nonpregnant, nonlactating, and have a negative serum pregnancy test before enrollment in the study. Female subjects of childbearing potential (including perimenopausal women who have had menstrual bleeding within 1 year) must be using appropriate birth control (abstinence and/or barrier methods and/or oral, injectable, or implantable hormonal contraceptives) during the entire duration of the study. Women are considered of non-childbearing potential if they are menopausal (last menstrual period greater than 12 months before Check in and a serum follicle stimulating hormone level greater than 40 mIU/mL) or have been surgically sterilized (documented hysterectomy, tubal ligation, or bilateral oophorectomy) at least 6 weeks before Check in.
- Subject has a body mass index of 18.0 to 30.0 kg/m2, inclusive.
- Subject provides written informed consent.
- Subject is willing and able to comply with all study requirements.
Key exclusion criteria (17 listed)
- Subject is currently participating in another clinical study of an investigational drug (or a medical device), or has participated in a study of this type within 30 days before Check in.
- Subject has a history or current evidence of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at the time of dosing or mild allergic reactions to drugs other than those listed in exclusion criterion #16), hematologic, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurologic disease. Exceptions to these criteria (eg, stable mild joint disease, cholecystectomy, or childhood asthma) may be made after discussion with the medical monitor.
- Subject has used any prescribed or over the counter medication without the approval of the investigator or sponsor within 1 week before the first dose of study drug (including dietary supplements, herbal remedies, and medications known to prolong the QT/corrected QT [QTc] interval).
- Subject is receiving any anticoagulant (eg, coumadin, heparin, low molecular weight heparin) or has received any anticoagulant within 3 months before Check in. Subjects who are receiving any drugs that affect platelet function (eg, aspirin, including low-dose aspirin) will also be excluded.
- Subject has a history of drug or alcohol abuse or dependence within 1 year before Check in.
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 |
|---|---|---|
| DroxidopaAlso: L-DOPS, Northera600 mg, single oral dose | Drug | Droxidopa - Therapeutic |
| DroxidopaAlso: L-DOPS, Northera2000 mg, single oral dose | Drug | Droxidopa - Supratherapeutic Dose |
| MoxifloxacinAlso: Avelox400 mg, single oral dose | Drug | Moxifloxacin, Placebo |
| PlaceboAlso: sugar pill, shamPlacebo matching Droxidopa or Moxifloxacin | Drug | Placebo |
Primary outcome
ECG Effects
Time frame: Baseline to End of Treatment (12 days)
The primary ECG endpoint is the time matched, placebo adjusted change from Baseline in QT interval corrected using an individual correction method (QTcI) (ΔΔQTcI). The QTcI method provides an optimization of QT correction for HR as compared with fixed exponent approaches such as Bazett (QTcB) or Fridericia (QTcF).
1 secondary outcome
QTcF and QTcB (for historic reasons only), HR, and PR, QRS, and uncorrected QT intervals, change in ECG morphological patterns, and the correlation between the QTcI change and droxidopa plasma concentrations
Time frame: Baseline to End of Treatment (12 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 7 Mar 2012.
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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.
Thomas Hunt, MD principal investigator
PPD Phase I Clinic
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 Droxidopa and Moxifloxacin in people with QTc Interval, run by Chelsea Therapeutics 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 17 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 7 Mar 2012. 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?
ECG Effects (time frame: Baseline to End of Treatment (12 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 7 Mar 2012.