HIV/AIDSPhase 1NCT02164812
Study to Determine the Effect of Efavirenz on the ECG QTcF Interval in Healthy Subjects
A Phase 1 study testing Moxifloxacin and Efavirenz in people with HIV/AIDS, run by Bristol-Myers Squibb at 1 site in United States.
Trial summary
The purpose of this study is to determine whether multiple doses of Efavirenz has an effect on the QTc interval (corrected by Fridericia) in CYP2B6 *1/*6 and *6/*6 healthy subjects. Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV/AIDS
- What is being tested?
- Moxifloxacin and Efavirenz
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to Aug 2015
- 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 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy volunteers, ages 18 to 49 years old
- BMI 18 to 32 kg/m2
- Women must not be pregnant or breastfeeding
Who cannot join
- A personal history of clinically relevant cardiac disease, symptomatic or asymptomatic arrhythmias, presyncope or syncopal episodes, or additional risk factors for torsades de pointes (eg, heart failure)
- History of hypokalemia, personal history or family history of prolonged QT interval, or family history of sudden cardiac death at a young age
- Any of the following on 12-lead electrocardiogram (ECG) prior to study drug administration: PR ≥210 msec, QRS ≥120 msec, QT ≥500 msec, QTcF ≥450 msec, HR <45 bpm
- Second or third degree heart block prior to study drug
- Positive urine screen for drugs of abuse
- Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or Human Immunodeficiency Virus (HIV)-1, -2 antibody
- Any of the following lab results outside of the ranges specified below prior to dosing: Alanine aminotransferase (ALT) >upper limit of normal (ULN), aspartate aminotransferase (AST) >ULN, Total bilirubin >ULN, Direct bilirubin >ULN, Creatinine >ULN, Serum potassium <lower limit of normal (LLN), Serum magnesium <LLN
- History of allergy to Moxifloxacin, Efavirenz or related compounds
Trial locations and contacts
1 site in 1 country.
United States1 site
Parexel International - Baltimore Epcu
Baltimore, Maryland, 21225
About this study
Official title: A Study to Determine the Concentration-Electrocardiographic Effects of Efavirenz in Healthy Subjects Enriched for CYP2B6 Polymorphisms
The purpose of this study is to determine whether multiple doses of Efavirenz has an effect on the QTc interval (corrected by Fridericia) in CYP2B6 *1/*6 and *6/*6 healthy subjects.
Read the detailed description
CYP = Cytochrome p-450
Primary Purpose: Other: This is a Phase 1 clinical pharmacology thorough QT study being conducted as a post marketing requirement
- Conditions
- HIV/AIDS
- Being tested
- Moxifloxacin, Placebo, Efavirenz
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MoxifloxacinDrug
Also called Avelox®
PlaceboDrug
EfavirenzDrug
Also called Sustiva®, BMS-561525
| Study group | Role | What they receive |
|---|---|---|
| Moxifloxacin, Placebo, Efavirenz | Experimental | Moxifloxacin, Placebo, Efavirenz single dose as specified Receives: Drug: Moxifloxacin; Drug: Placebo; Drug: Efavirenz |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference from placebo of Efavirenz (EFV) in change from period-specific baseline in the QT interval corrected for heart rate (HR) via Fridericia's method (QTcF) at postdose extraction times (ΔΔQTcF)
QTcF = QT corrected for Fridericia's formula
Measured: Days 1, 2, 5, 6, 19 and 20
Secondary outcomes (8)
Difference from placebo of EFV in change from period-specific baseline in other ECG parameters: HR, PR, QRS, and uncorrected QT following 14 days of dosing
ECG = Electrocardiogram
Measured: Days 1, 5 and 19
Difference from placebo of Moxifloxacin in change from period-specific baseline in QTcF (ΔΔQTcF) following a single dose
Measured: Days 1, 5 and 19
Number and percent of subjects having a maximum QTcF, HR, PR, and QRS outside of pre-specified categories and those having a maximum ΔQTcF outside of pre-specified categories
Measured: Days 1, 5 and 19
Time of maximum observed plasma concentration (Tmax) of EFV
Measured: Days 1, 2, 19 and 20
Maximum observed plasma concentration (Cmax) of EFV
Measured: Days 1, 2, 19 and 20
Trough observed plasma concentration 24 h after a dose (C24) of EFV
Measured: Days 1, 2, 19 and 20
Area under the concentration-time curve in one dosing interval (AUC(TAU)) of EFV
Measured: Days 1, 2, 19 and 20
Safety based on incidence of AEs, SAEs, AEs leading to discontinuation, marked laboratory abnormalities, findings on 12-lead safety ECG measurements and physical examinations, and abnormalities in vital sign measurements exceeding pre-defined thresholds
Serious AE (SAE)
Measured: Up to 30 days after discontinuation of dose (approximately 52 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2014 (estimated)
- Study startJul 2014
- Primary completionAug 2015
- Study completionAug 2015
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 HIV/AIDSStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02164812
- Sponsor's protocol ID
- AI266-959
- Status last verified
- Sep 2015
- First submitted
- 13 Jun 2014
- Last updated
- 7 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Abdelhady AM, Shugg T, Thong N, Lu JB, Kreutz Y, Jaynes HA, Robarge JD, Tisdale JE, Desta Z, Overholser BR. Efavirenz Inhibits the Human Ether-A-Go-Go Related Current (hERG) and Induces QT Interval Prolongation in CYP2B6*6*6 Allele Carriers. J Cardiovasc Electrophysiol. 2016 Oct;27(10):1206-1213. doi: 10.1111/jce.13032. Epub 2016 Jul 25.
PubMed 27333947
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Determine the Concentration-Electrocardiographic Effects of Efavirenz in Healthy Subjects Enriched for CYP2B6 Polymorphisms
- ClinicalTrials.gov ID
- NCT02164812
- Acronym / sponsor ID
- AI266-959
- Conditions
- HIV/AIDS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Jul 2014
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 17 Jun 2014 (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 determine whether multiple doses of Efavirenz has an effect on the QTc interval (corrected by Fridericia) in CYP2B6 *1/*6 and *6/*6 healthy subjects.
Detailed description
CYP = Cytochrome p-450
Primary Purpose: Other: This is a Phase 1 clinical pharmacology thorough QT study being conducted as a post marketing requirement
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Moxifloxacin, Placebo, Efavirenz | Experimental | Drug: Moxifloxacin, Drug: Placebo, Drug: EfavirenzMoxifloxacin, Placebo, Efavirenz single dose as specified |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy volunteers, ages 18 to 49 years old
- BMI 18 to 32 kg/m2
- Women must not be pregnant or breastfeeding
Key exclusion criteria (8 listed)
- A personal history of clinically relevant cardiac disease, symptomatic or asymptomatic arrhythmias, presyncope or syncopal episodes, or additional risk factors for torsades de pointes (eg, heart failure)
- History of hypokalemia, personal history or family history of prolonged QT interval, or family history of sudden cardiac death at a young age
- Any of the following on 12-lead electrocardiogram (ECG) prior to study drug administration: PR ≥210 msec, QRS ≥120 msec, QT ≥500 msec, QTcF ≥450 msec, HR <45 bpm
- Second or third degree heart block prior to study drug
- Positive urine screen for drugs of abuse
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 |
|---|---|---|
| MoxifloxacinAlso: Avelox® | Drug | Moxifloxacin, Placebo, Efavirenz |
| Placebo | Drug | Moxifloxacin, Placebo, Efavirenz |
| EfavirenzAlso: Sustiva®, BMS-561525 | Drug | Moxifloxacin, Placebo, Efavirenz |
Primary outcome
Difference from placebo of Efavirenz (EFV) in change from period-specific baseline in the QT interval corrected for heart rate (HR) via Fridericia's method (QTcF) at postdose extraction times (ΔΔQTcF)
Time frame: Days 1, 2, 5, 6, 19 and 20
QTcF = QT corrected for Fridericia's formula
8 secondary outcomes
Difference from placebo of EFV in change from period-specific baseline in other ECG parameters: HR, PR, QRS, and uncorrected QT following 14 days of dosing
Time frame: Days 1, 5 and 19
Difference from placebo of Moxifloxacin in change from period-specific baseline in QTcF (ΔΔQTcF) following a single dose
Time frame: Days 1, 5 and 19
Number and percent of subjects having a maximum QTcF, HR, PR, and QRS outside of pre-specified categories and those having a maximum ΔQTcF outside of pre-specified categories
Time frame: Days 1, 5 and 19
Time of maximum observed plasma concentration (Tmax) of EFV
Time frame: Days 1, 2, 19 and 20
Maximum observed plasma concentration (Cmax) of EFV
Time frame: Days 1, 2, 19 and 20
Trough observed plasma concentration 24 h after a dose (C24) of EFV
Time frame: Days 1, 2, 19 and 20
Area under the concentration-time curve in one dosing interval (AUC(TAU)) of EFV
Time frame: Days 1, 2, 19 and 20
Safety based on incidence of AEs, SAEs, AEs leading to discontinuation, marked laboratory abnormalities, findings on 12-lead safety ECG measurements and physical examinations, and abnormalities in vital sign measurements exceeding pre-defined thresholds
Time frame: Up to 30 days after discontinuation of dose (approximately 52 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 Sep 2015.
- Derived from this study: PubMed 27333947Abdelhady AM, Shugg T, Thong N, Lu JB, Kreutz Y, Jaynes HA, Robarge JD, Tisdale JE, Desta Z, Overholser BR. Efavirenz Inhibits the Human Ether-A-Go-Go Related Current (hERG) and Induces QT Interval Prolongation in CYP2B6*6*6 Allele Carriers. J Cardiovasc Electrophysiol. 2016 Oct;27(10):1206-1213. doi: 10.1111/jce.13032. Epub 2016 Jul 25.
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
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 Moxifloxacin and Efavirenz in people with HIV/AIDS, run by Bristol-Myers Squibb 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 3 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 7 Sep 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. 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?
Difference from placebo of Efavirenz (EFV) in change from period-specific baseline in the QT interval corrected for heart rate (HR) via Fridericia's method (QTcF) at postdose extraction times (ΔΔQTcF) (time frame: Days 1, 2, 5, 6, 19 and 20). 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 NCT02164812, 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 7 Sep 2015.