Healthy SubjectsPhase 1NCT01297062

A Safety Study to Assess the Effects of Therapeutic and Supratherapeutic Exenatide Concentrations on QT Interval in Healthy Subjects

A Phase 1 study testing Exenatide and Moxifloxacin in people with Healthy Subjects, run by AstraZeneca at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Compare the effect of exenatide (therapeutic and supratherapeutic concentrations), moxifloxacin and placebo on the QT interval. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Subjects
What is being tested?: Exenatide and Moxifloxacin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 94 participants
Where: 2 sitesUnited States
Study dates: Feb 2011to May 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Is overtly healthy, as determined by medical history and physical examination
Has body mass index (BMI) between 25 and 35 kg/m2
Has fasting serum glucose <110 mg/dL
Has no clinically significant blood pressure or heart rate readings as judged by the investigator at study start
Has electrocardiogram (ECG) results judged as not clinically significant by the investigator at study start

Who cannot join

Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being
Has an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risk of participating in the study, such as a Bazett's corrected QT (QTcB) interval >450 ms.
Family history of sudden death
Personal history of unexplained syncope within last year, or family history of Long QT Syndrome, or significant active cardiac disease, or symptoms of angina pectoris or transient ischemic attacks within the previous 6 months

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Research Site
Daytona Beach, Florida
Research Site
Evansville, Indiana

Other trials in United States

About this study

Official title: A Randomized, Phase 1, Three-Period, Placebo- and Positive-Controlled, Double-Blind, Crossover Study to Assess the Electrophysiological Effects of Exenatide at Therapeutic and Supratherapeutic Concentrations on the 12-Lead Electrocardiogram QT Interval in Healthy Subjects

Compare the effect of exenatide (therapeutic and supratherapeutic concentrations), moxifloxacin and placebo on the QT interval.

Conditions: Healthy Subjects
Being tested: Exenatide, Moxifloxacin, Placebo comparator
Keywords: Diabetes, exenatide, Amylin, Lilly, QT interval
Medical subject headings: Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ExenatideDrug
IV Exenatide (therapeutic and supratherapeutic concentrations)
MoxifloxacinDrug
Oral Moxifloxacin (400 mg)
Placebo comparatorDrug
IV Placebo (matching volume of placebo)

Study groups in NCT01297062
Study group	Role	What they receive
Exenatide	Experimental	Not described Receives: Drug: Exenatide
Placebo	Placebo comparator	Not described Receives: Drug: Placebo comparator
Moxifloxacin	Active comparator	Not described Receives: Drug: Moxifloxacin

What is being measured

The primary outcome is the main question the study is designed to answer.

Comparison of Least Squares (LS) Mean Changes From Baseline in Population-based Corrected QT Intervals (QTcP) Between Exenatide and Placebo on Day 1 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 200 pg/mL)
Factors in QT correction formulas were first estimated using pre-therapy data. The most appropriate correction method (QTcP) minimized the mean squared individual QTc/RR regression slope with on-exenatide data. Adequacy of correction was validated with on-placebo data. Change from baseline in QTcP was analyzed by a mixed-effects model for repeated measures (MMRM) between exenatide and placebo.
Measured: Baseline, Day 1
Comparison of LS Mean Changes From Baseline in QTcP Intervals Between Exenatide and Placebo on Day 2 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 300 pg/mL)
Factors in QT correction formulas were first estimated using pre-therapy data. The most appropriate correction method (QTcP) minimized the mean squared individual QTc/RR regression slope with on-exenatide data. Adequacy of correction was validated with on-placebo data. Change from baseline in QTcP was analyzed by a MMRM between exenatide and placebo.
Measured: Baseline, Day 2
Comparison of LS Mean Changes From Baseline in QTcP Intervals Between Exenatide and Placebo on Day 3 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 500 pg/mL)
Factors in QT correction formulas were first estimated using pre-therapy data. The most appropriate correction method (QTcP) minimized the mean squared individual QTc/RR regression slope with on-exenatide data. Adequacy of correction was validated with on-placebo data. Change from baseline in QTcP was analyzed by a MMRM between exenatide and placebo.
Measured: Baseline, Day 3

Secondary outcomes (6)

Assay Sensitivity of Moxifloxacin at 1000h (1 Hour Post-administration of Moxifloxacin) on Day 2
Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo.
Measured: Baseline, Day 2
Assay Sensitivity of Moxifloxacin at 1100h (2 Hour Post-administration of Moxifloxacin) on Day 2
Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo.
Measured: Baseline, Day 2
Assay Sensitivity of Moxifloxacin at 1200h (3 Hour Post-administration of Moxifloxacin) on Day 2
Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo.
Measured: Baseline, Day 2
Number of Subjects With QTcP Interval >450msec at Any Timepoint on Any Day in Exenatide and Placebo
Number of subjects with QTcP > 450 msec at any timepoint on any day was summarized by frequency for exenatide and placebo.
Measured: Day 1, 2, or 3
Number of Subjects With Increase of QTcP Interval From Baseline >30msec at Any Timepoint on Any Day in Exenatide and Placebo
Number of subjects with increase of QTcP interval from baseline >30 msec at any timepoint on any day was summarized by frequency for exenatide and placebo.
Measured: Baseline, Day 1, 2, or 3
Plasma Exenatide Concentrations at Steady State on Day 1, 2 and 3
The plasma exenatide concentration at steady state was descriptively summarized by geometric mean, standard error, and its effect on placebo-adjusted change from baseline in QTcP was assessed.
Measured: Baseline, Day 1, 2, and 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2011May 2011

First posted16 Feb 2011 (estimated)
Study startFeb 2011
Primary completionApr 2011
Study completionMay 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Healthy SubjectsStudies of the same condition, open and under way.
More trials run by AstraZenecaThe 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: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 94 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01297062
Sponsor's protocol ID: BCB112
Status last verified: Mar 2015
First submitted: 9 Feb 2011
Last updated: 14 Apr 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 14 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Phase 1, Three-Period, Placebo- and Positive-Controlled, Double-Blind, Crossover Study to Assess the Electrophysiological Effects of Exenatide at Therapeutic and Supratherapeutic Concentrations on the 12-Lead Electrocardiogram QT Interval in Healthy Subjects
ClinicalTrials.gov ID: NCT01297062
Acronym / sponsor ID: BCB112
Conditions: Healthy Subjects
Keywords: Diabetes, exenatide, Amylin, Lilly, QT interval
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 94 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: Feb 2011
Primary completion: Apr 2011 (actual)
Study completion: May 2011 (actual)
First posted: 16 Feb 2011 (estimated)
Results: Posted 31 May 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Compare the effect of exenatide (therapeutic and supratherapeutic concentrations), moxifloxacin and placebo on the QT interval.

Study design

Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Exenatide	Experimental	Drug: Exenatide
Placebo	Placebo comparator	Drug: Placebo comparator
Moxifloxacin	Active comparator	Drug: Moxifloxacin

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Is overtly healthy, as determined by medical history and physical examination
Has body mass index (BMI) between 25 and 35 kg/m2
Has fasting serum glucose <110 mg/dL
Has no clinically significant blood pressure or heart rate readings as judged by the investigator at study start
Has electrocardiogram (ECG) results judged as not clinically significant by the investigator at study start

Key exclusion criteria (4 listed)

Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being
Has an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risk of participating in the study, such as a Bazett's corrected QT (QTcB) interval >450 ms.
Family history of sudden death
Personal history of unexplained syncope within last year, or family history of Long QT Syndrome, or significant active cardiac disease, or symptoms of angina pectoris or transient ischemic attacks 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
ExenatideIV Exenatide (therapeutic and supratherapeutic concentrations)	Drug	Exenatide
MoxifloxacinOral Moxifloxacin (400 mg)	Drug	Moxifloxacin
Placebo comparatorIV Placebo (matching volume of placebo)	Drug	Placebo

Primary outcome

Comparison of Least Squares (LS) Mean Changes From Baseline in Population-based Corrected QT Intervals (QTcP) Between Exenatide and Placebo on Day 1 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 200 pg/mL)
Time frame: Baseline, Day 1
Factors in QT correction formulas were first estimated using pre-therapy data. The most appropriate correction method (QTcP) minimized the mean squared individual QTc/RR regression slope with on-exenatide data. Adequacy of correction was validated with on-placebo data. Change from baseline in QTcP was analyzed by a mixed-effects model for repeated measures (MMRM) between exenatide and placebo.
Comparison of LS Mean Changes From Baseline in QTcP Intervals Between Exenatide and Placebo on Day 2 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 300 pg/mL)
Time frame: Baseline, Day 2
Factors in QT correction formulas were first estimated using pre-therapy data. The most appropriate correction method (QTcP) minimized the mean squared individual QTc/RR regression slope with on-exenatide data. Adequacy of correction was validated with on-placebo data. Change from baseline in QTcP was analyzed by a MMRM between exenatide and placebo.
Comparison of LS Mean Changes From Baseline in QTcP Intervals Between Exenatide and Placebo on Day 3 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 500 pg/mL)
Time frame: Baseline, Day 3
Factors in QT correction formulas were first estimated using pre-therapy data. The most appropriate correction method (QTcP) minimized the mean squared individual QTc/RR regression slope with on-exenatide data. Adequacy of correction was validated with on-placebo data. Change from baseline in QTcP was analyzed by a MMRM between exenatide and placebo.

6 secondary outcomes

Assay Sensitivity of Moxifloxacin at 1000h (1 Hour Post-administration of Moxifloxacin) on Day 2
Time frame: Baseline, Day 2
Assay Sensitivity of Moxifloxacin at 1100h (2 Hour Post-administration of Moxifloxacin) on Day 2
Time frame: Baseline, Day 2
Assay Sensitivity of Moxifloxacin at 1200h (3 Hour Post-administration of Moxifloxacin) on Day 2
Time frame: Baseline, Day 2
Number of Subjects With QTcP Interval >450msec at Any Timepoint on Any Day in Exenatide and Placebo
Time frame: Day 1, 2, or 3
Number of Subjects With Increase of QTcP Interval From Baseline >30msec at Any Timepoint on Any Day in Exenatide and Placebo
Time frame: Baseline, Day 1, 2, or 3
Plasma Exenatide Concentrations at Steady State on Day 1, 2 and 3
Time frame: Baseline, Day 1, 2, and 3

Results and safety

Results posted to the registry on 31 May 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo-Exenatide-Moxifloxacin Sequence	15	11
Exenatide-Moxifloxacin-Placebo Sequence	14	13
Moxifloxacin-Placebo-Exenatide Sequence	14	12
Moxifloxacin-Exenatide-Placebo Sequence	14	13
Placebo-Moxifloxacin-Exenatiden Sequence	15	13
Exenatide-Placebo-Moxifloxacin Sequence	14	13
Non-Randomized	8	0

Primary outcome: Comparison of Least Squares (LS) Mean Changes From Baseline in Population-based Corrected QT Intervals (QTcP) Between Exenatide and Placebo on Day 1 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 200 pg/mL)

Time frame: Baseline, Day 1. Least squares mean (90% Confidence Interval). Unit: msec

Measure	Exenatide n = 74	Placebo n = 74
Value	-2.25 (0.636)	-0.89 (0.599)

Exenatide vs Placebo: Least Squares Mean Difference: -1.36 (90% CI -2.21 to -0.50), Mixed Models Analysis

Population analysed: Evaluable Population included all ITT subjects who completed all ECG assessment periods and have valid ECG measurements and no vomiting in any ECG data extraction window. No missing value was imputed.

Primary outcome: Comparison of LS Mean Changes From Baseline in QTcP Intervals Between Exenatide and Placebo on Day 2 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 300 pg/mL)

Time frame: Baseline, Day 2. Least squares mean (90% Confidence Interval). Unit: msec

Measure	Exenatide n = 74	Placebo n = 74
Value	-2.58 (0.640)	-0.56 (0.596)

Exenatide vs Placebo: Least Squares Mean Difference: -2.02 (90% CI -2.88 to -1.16), Mixed Models Analysis

Population analysed: Evaluable Population. No imputation for missing value was used.

Primary outcome: Comparison of LS Mean Changes From Baseline in QTcP Intervals Between Exenatide and Placebo on Day 3 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 500 pg/mL)

Time frame: Baseline, Day 3. Least squares mean (90% Confidence Interval). Unit: msec

Measure	Exenatide n = 74	Placebo n = 74
Value	-3.54 (0.675)	-2.41 (0.623)

Exenatide vs Placebo: Least Squares Mean Difference: -1.13 (90% CI -2.11 to -0.15), Mixed Models Analysis

Population analysed: Evaluable Population. No imputation for missing value was used.

6 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Exenatide	0 of 80 (0%)	65 of 80 (81.3%)	Not reported
Placebo	0 of 84 (0%)	10 of 84 (11.9%)	Not reported
Moxifloxacin	1 of 80 (1.3%)	8 of 80 (10%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Vice President Research and Development, MD study director

Amylin Pharmaceuticals, LLC.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Exenatide and Moxifloxacin in people with Healthy Subjects, run by AstraZeneca at 2 sites 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 5 inclusion and 4 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 14 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

Yes. Results are posted in the registry (first posted 31 May 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Comparison of Least Squares (LS) Mean Changes From Baseline in Population-based Corrected QT Intervals (QTcP) Between Exenatide and Placebo on Day 1 Averaged Over 1300h, 1400h, 1500h (Target Steady State Exenatide Concentration of 200 pg/mL) (time frame: Baseline, Day 1). The study lists 3 primary outcomes in all. 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 NCT01297062.

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 14 Apr 2015; AzTrials last refreshed its copy on 7 Nov 2026.