Ventricular RepolarizationPhase 1NCT01812538
A Randomized, Single-Dose, Comparative, Positive and Placebo Controlled, Four-Way, Four Period, Cross-Over Study to Evaluate the Effect of DIC075V on QTc Intervals in Healthy Subjects
A Phase 1 study testing DIC075V in people with Ventricular Repolarization, run by Hospira, now a wholly owned subsidiary of Pfizer at 1 site in United States.
Trial summary
This study is conducted to evaluate the effectiveness of DIC075V on ventricular repolarization in healthy subjects compared to placebo after a single dose of DIC075V administered intravenously (IV) and to evaluate ECG assay sensitivity by evaluating the baseline-adjusted effect of a single oral (PO) moxifloxacin 400… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Ventricular Repolarization
- What is being tested?
- DIC075V
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- May 2009to Jul 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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Willing and able to provide signed informed consent, including Health Insurance Portability and Accountability Act (HIPAA) Authorization.
- Healthy adult male and/or female subjects, 18-50 years of age.
- Body mass index (BMI) between 18-30, inclusive.
- Medically healthy with no clinically significant screening results (laboratory profiles, medical histories, ECGs, physical exam).
- Normal blood pressure (<140 mmHg systolic and <90 mmHg diastolic).
- Normal 12-lead ECG (QTc interval <450 millisecond (ms) for males and <470 ms for females):
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- Consistent sinus rhythm
- No clinically significant conduction disorders
- PR interval between 120 and 230 ms
- HR ≤100 bpm and ≥40 bpm
- QRS interval ≤110 ms
- QT intervals that can be consistently analyzed.
- No medical history of cardiac disease or a family history of QT prolongation.
- No clinically significant electrolyte abnormality.
- Subjects with a calculated creatinine clearance greater than >80 ml/min.
- Female subjects who are of childbearing potential with a negative serum pregnancy test at Screening and at Check-in who are either sexually inactive (abstinent) for 14 days prior to Screening and throughout the study or are using two of the following acceptable birth control methods:
- Intrauterine device (IUD) in place for at least 2 months prior to Study Day -2;
- Barrier method (condom or diaphragm) with spermicide for at least 14 days prior to screening through study completion;
- Hormonal contraceptive for at least 3 months prior to Study Day -2 through completion of study;
- Surgical sterilization (vasectomy) of partner at least 6 months prior to Study Day -2.
- Female subjects who are of non-childbearing potential with a negative serum pregnancy test at Screening and Check-in and meet at least one of the following criteria:
- Naturally postmenopausal for a minimum of 2 consecutive years prior to Study Day -2;
- Surgically sterile (bilateral tubal ligation with surgery at least 6 months prior to Study Day -2, hysterectomy, or bilateral oophorectomy with surgery at least 2 months prior to Study Day -2).
Who cannot join
- History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease.
- History of invasive cancer within the past 5 years (excluding non-melanoma skin cancers).
- History of hypersensitivity or allergy to the quinolone class of antibiotics; to diclofenac or other NSAIDs; or to HPβCD or other excipients in DIC075V (monothioglycerol, sodium hydroxide, hydrochloric acid, and water for injection).
- History or presence of alcoholism or drug abuse within the past 2 years.
- Use of tobacco products within the previous 6 months.
- Donation of blood within 45 days prior to Study Day -2.
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- Plasma donation within 30 days prior to Study Day -2.
- Participation in a study of an investigational drug within 90 days prior to Study Day -2.
- Participation in another clinical trial within 45 days prior to Study Day -2.
- Female subjects who are pregnant or lactating.
- Hemoglobin below the reference range for the testing laboratory.
- Clinically significant abnormal laboratory values.
- Abnormal ECG. The abnormality of the ECG could be a QRS duration of >110 ms, a first degree heart block defined as a PR duration >230 ms, second or third degree heart block, or a complete heart block.
- Male subjects with a screening QTc interval ≥450 ms and female subjects with a QTc interval ≥470 ms.
- Presence of untreated or uncontrolled blood pressure, i.e., systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg.
- Angina, uncontrolled hypertension, clinically significant bradycardia, clinically significant cardiac arrhythmias, or any other clinically significant cardiovascular abnormality.
- History of clinically significant syncope.
- History of any clinically significant arrhythmias (e.g., ventricular arrhythmias, supra-ventricular arrhythmias, or atrial fibrillation).
- History of clinically significant psychiatric illness that would prevent the subject from providing a valid Informed Consent.
- Positive laboratory test results for hepatitis B, hepatitis C, HIV, controlled Substances, cotinine, or alcohol.
- With the exception of hormonal contraceptives or hormone replacement therapy for females for at least 3 months piror to Study Day -2, any prescription or over-the-counter (OTC) medications, including topical medications, vitamins, herbal or dietary supplements/remedies (e.g., Saint John's Wort or Milk Thistle), within 14 days of Study Day -2.
- With the exception of hormonal contraceptives or hormone replacement therapy for females for at least 3 months prior to Study Day -2, any planned concomitant medication for the duration of the study (except for acetaminophen up to 2 g/day).
- History of additional risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia, history of drowning survival, family history of Long QT Syndrome, family history of Short QT Syndrome, or family history of unexplainable early sudden death).
- History of asthma attack, hives, or other allergic reactions to aspirin or other NSAID medicines.
- History of a coronary bypass operation.
- History of a bleeding gastric or duodenal ulcer.
- History of skin reactions to the taking of any medications.
- History of hepatic disorders and any symptoms associated with a hepatic disorders, e.g., nausea, tiredness, itching, flu-like symptoms, vomiting of blood, blood in the subject's bowel movements, and/or melana.
- History of clinically significant seizures.
Trial locations and contacts
1 site in 1 country.
About this study
This study is conducted to evaluate the effectiveness of DIC075V on ventricular repolarization in healthy subjects compared to placebo after a single dose of DIC075V administered intravenously (IV) and to evaluate ECG assay sensitivity by evaluating the baseline-adjusted effect of a single oral (PO) moxifloxacin 400 mg dose on ventricular repolarization in healthy subjects compared to placebo. Other secondary objectives are as follows:
- To evaluate the effect of DIC075V on ventricular repolarization in healthy subjects compared to placebo at the Tmax of diclofenac and hydroxypropyl-β-cyclodextrin (HPβCD).
- To determine if there is a pharmacokinetic/pharmacodynamic (PK/PD) relationship between the duration of the QTc intervals and diclofenac and HPβCD plasma concentrations.
- Obtain additional pharmacokinetic (PK) information on diclofenac and HPβCD in healthy subjects.
- Provide additional safety information.
Read the detailed description
This is a randomized, single-dose, comparative, positive and placebo controlled, 4 period, 4-way crossover study evaluating the effect of DIC075V on QTc intervals in healthy subjects. Two doses of DIC075V are tested and include moxifloxicin as a positive control and normal saline as the placebo arm. On 4 separate occasions separated by at least 72 hours, subjects are given single IV or oral (moxifloxicin) treatments. ECGs are acquired from a continuous Holter monitor and selected timepoints will be evaluated. These ECGs will be 15 seconds in duration and extracted in triplicate. Monitoring will continue for 24 hours with each treatment. The primary ECG endpoint is the baseline-adjusted QTc using the Fridericia correction (QTcF). Secondary endpoints include the baseline-adjusted QTc using the Bazett correction formula (QTcB). In addition, a population-specific regression model will be constructed with QT plotted against RR (the time elapsed between 2 consecutive R-waves). Finally, QT parameters are explored graphically in relation to PK variables Cmax, Tmax and AUC.
- Conditions
- Ventricular Repolarization
- Being tested
- DIC075V
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DIC075VDrug
Also called Voltaren, Voltarol, Cataflam, Zipsor
Four single dose treatments:
- Placebo (normal saline)
- Moxifloxacin (positive control)
- DIC075V 37.5 mg
- DIC075V 75 mg
All subjects receive each of the 4 treatments.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo Receives: Drug: DIC075V |
| Experimental 1 | Experimental | DIC075V 37.5 mg Receives: Drug: DIC075V |
| Experimental 2 | Experimental | DIC075V 75 mg Receives: Drug: DIC075V |
| Active control | Active comparator | Moxifloxacin hydrochloride 400 mg Receives: Drug: DIC075V |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time-matched active drug-placebo difference in baseline-adjusted QTc interval
The primary ECG endpoint is the time-matched active drug-placebo difference in baseline-adjusted QTc interval using the Fridericia correction formula (QTcF). The QTcF is evaluated at the time point where the maximal baseline and placebo-adjusted value is observed. These measurements are consistent with ICH E14 guidance.
Measured: At -1.5, -1.0, and -0.5 hours (pre-dose), and 5, 10, 15, and 30 minutes (2-min window) and 1, 2, 4, 6, 8, 12, and 23.5 hours (5-min window) on Study Days 1, 4, 7, and 10.
Secondary outcomes (3)
Time-matched active drug-placebo difference in baseline-adjusted QTc interval using the Bazett's correction formula (QTcB) evaluated at the timepoint where the maximum mean baseline- and placebo-adjusted QTcB is observed for each active treatment arm
Measured: At -1.5, -1.0, and -0.5 hours (pre-dose), and 5, 10, 15, and 30 minutes (2-min window) and 1, 2, 4, 6, 8, 12, and 23.5 hours (5-min window) on Study Days 1, 4, 7, and 10.
Time matched active drug-placebo difference in baseline adjusted QTcF at the subject-specific Tmax or the next available ECG timepoint
Measured: At -1.5, -1.0, and -0.5 hours (pre-dose), and 5, 10, 15, and 30 minutes (2-min window) and 1, 2, 4, 6, 8, 12, and 23.5 hours (5-min window) on Study Days 1, 4, 7, and 10.
Time-matched active drug-placebo difference in the maximum baseline-adjusted QTcF of each subject at each active treatment period.
Measured: At -1.5, -1.0, and -0.5 hours (pre-dose), and 5, 10, 15, and 30 minutes (2-min window) and 1, 2, 4, 6, 8, 12, and 23.5 hours (5-min window) on Study Days 1, 4, 7, and 10.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2013 (estimated)
- Study startMay 2009
- Primary completionJul 2009
- Study completionJul 2009
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 Ventricular RepolarizationStudies 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
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospira, now a wholly owned subsidiary of Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01812538
- Sponsor's protocol ID
- DFC-011
- Status last verified
- Jul 2015
- First submitted
- 14 Mar 2013
- Last updated
- 24 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Carr DB, McDonnell Moorehead T, Bouchard A, Sprenger CR, Hamilton DA, Lang E, Madden D, Lacouture PG, Wright C 4th. Effects of injectable HPbetaCD-diclofenac on the human delayed rectifier potassium channel current in vitro and on proarrhythmic QTc in vivo. Clin Ther. 2013 May;35(5):646-58. doi: 10.1016/j.clinthera.2013.03.014. Epub 2013 Apr 8.
PubMed 23578606
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Single-Dose, Comparative, Positive and Placebo Controlled, Four-Way, Four Period, Cross-Over Study to Evaluate the Effect of DIC075V on QTc Intervals in Healthy Subjects
- ClinicalTrials.gov ID
- NCT01812538
- Acronym / sponsor ID
- DFC-011
- Conditions
- Ventricular Repolarization
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Hospira, now a wholly owned subsidiary of PfizerIndustry (pharma, biotech, devices)
- Study start
- May 2009
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 18 Mar 2013 (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 conducted to evaluate the effectiveness of DIC075V on ventricular repolarization in healthy subjects compared to placebo after a single dose of DIC075V administered intravenously (IV) and to evaluate ECG assay sensitivity by evaluating the baseline-adjusted effect of a single oral (PO) moxifloxacin 400 mg dose on ventricular repolarization in healthy subjects compared to placebo. Other secondary objectives are as follows:
- To evaluate the effect of DIC075V on ventricular repolarization in healthy subjects compared to placebo at the Tmax of diclofenac and hydroxypropyl-β-cyclodextrin (HPβCD).
- To determine if there is a pharmacokinetic/pharmacodynamic (PK/PD) relationship between the duration of the QTc intervals and diclofenac and HPβCD plasma concentrations.
- Obtain additional pharmacokinetic (PK) information on diclofenac and HPβCD in healthy subjects.
- Provide additional safety information.
Detailed description
This is a randomized, single-dose, comparative, positive and placebo controlled, 4 period, 4-way crossover study evaluating the effect of DIC075V on QTc intervals in healthy subjects. Two doses of DIC075V are tested and include moxifloxicin as a positive control and normal saline as the placebo arm. On 4 separate occasions separated by at least 72 hours, subjects are given single IV or oral (moxifloxicin) treatments. ECGs are acquired from a continuous Holter monitor and selected timepoints will be evaluated. These ECGs will be 15 seconds in duration and extracted in triplicate. Monitoring will continue for 24 hours with each treatment. The primary ECG endpoint is the baseline-adjusted QTc using the Fridericia correction (QTcF). Secondary endpoints include the baseline-adjusted QTc using the Bazett correction formula (QTcB). In addition, a population-specific regression model will be constructed with QT plotted against RR (the time elapsed between 2 consecutive R-waves). Finally, QT parameters are explored graphically in relation to PK variables Cmax, Tmax and AUC.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: DIC075VPlacebo |
| Experimental 1 | Experimental | Drug: DIC075VDIC075V 37.5 mg |
| Experimental 2 | Experimental | Drug: DIC075VDIC075V 75 mg |
| Active control | Active comparator | Drug: DIC075VMoxifloxacin hydrochloride 400 mg |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (23 listed)
- Willing and able to provide signed informed consent, including Health Insurance Portability and Accountability Act (HIPAA) Authorization.
- Healthy adult male and/or female subjects, 18-50 years of age.
- Body mass index (BMI) between 18-30, inclusive.
- Medically healthy with no clinically significant screening results (laboratory profiles, medical histories, ECGs, physical exam).
- Normal blood pressure (<140 mmHg systolic and <90 mmHg diastolic).
Key exclusion criteria (29 listed)
- History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease.
- History of invasive cancer within the past 5 years (excluding non-melanoma skin cancers).
- History of hypersensitivity or allergy to the quinolone class of antibiotics; to diclofenac or other NSAIDs; or to HPβCD or other excipients in DIC075V (monothioglycerol, sodium hydroxide, hydrochloric acid, and water for injection).
- History or presence of alcoholism or drug abuse within the past 2 years.
- Use of tobacco products within the previous 6 months.
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 |
|---|---|---|
| DIC075VAlso: Voltaren, Voltarol, Cataflam, ZipsorFour single dose treatments: * Placebo (normal saline) * Moxifloxacin (positive control) * DIC075V 37.5 mg * DIC075V 75 mg All subjects receive each of the 4 treatments. | Drug | Active control, Experimental 1, Experimental 2, Placebo |
Primary outcome
Time-matched active drug-placebo difference in baseline-adjusted QTc interval
Time frame: At -1.5, -1.0, and -0.5 hours (pre-dose), and 5, 10, 15, and 30 minutes (2-min window) and 1, 2, 4, 6, 8, 12, and 23.5 hours (5-min window) on Study Days 1, 4, 7, and 10.
The primary ECG endpoint is the time-matched active drug-placebo difference in baseline-adjusted QTc interval using the Fridericia correction formula (QTcF). The QTcF is evaluated at the time point where the maximal baseline and placebo-adjusted value is observed. These measurements are consistent with ICH E14 guidance.
3 secondary outcomes
Time-matched active drug-placebo difference in baseline-adjusted QTc interval using the Bazett's correction formula (QTcB) evaluated at the timepoint where the maximum mean baseline- and placebo-adjusted QTcB is observed for each active treatment arm
Time frame: At -1.5, -1.0, and -0.5 hours (pre-dose), and 5, 10, 15, and 30 minutes (2-min window) and 1, 2, 4, 6, 8, 12, and 23.5 hours (5-min window) on Study Days 1, 4, 7, and 10.
Time matched active drug-placebo difference in baseline adjusted QTcF at the subject-specific Tmax or the next available ECG timepoint
Time frame: At -1.5, -1.0, and -0.5 hours (pre-dose), and 5, 10, 15, and 30 minutes (2-min window) and 1, 2, 4, 6, 8, 12, and 23.5 hours (5-min window) on Study Days 1, 4, 7, and 10.
Time-matched active drug-placebo difference in the maximum baseline-adjusted QTcF of each subject at each active treatment period.
Time frame: At -1.5, -1.0, and -0.5 hours (pre-dose), and 5, 10, 15, and 30 minutes (2-min window) and 1, 2, 4, 6, 8, 12, and 23.5 hours (5-min window) on Study Days 1, 4, 7, and 10.
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 Jul 2015.
- Derived from this study: PubMed 23578606Carr DB, McDonnell Moorehead T, Bouchard A, Sprenger CR, Hamilton DA, Lang E, Madden D, Lacouture PG, Wright C 4th. Effects of injectable HPbetaCD-diclofenac on the human delayed rectifier potassium channel current in vitro and on proarrhythmic QTc in vivo. Clin Ther. 2013 May;35(5):646-58. doi: 10.1016/j.clinthera.2013.03.014. Epub 2013 Apr 8.
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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 DIC075V in people with Ventricular Repolarization, run by Hospira, now a wholly owned subsidiary of Pfizer 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 23 inclusion and 29 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 Jul 2015. 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?
Time-matched active drug-placebo difference in baseline-adjusted QTc interval (time frame: At -1.5, -1.0, and -0.5 hours (pre-dose), and 5, 10, 15, and 30 minutes (2-min window) and 1, 2, 4, 6, 8, 12, and 23.5 hours (5-min window) on Study Days 1, 4, 7, and 10.). 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 NCT01812538, 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 Jul 2015; AzTrials last refreshed its copy on 27 Oct 2026.