Trial · Interventional

CompletedPhase 1Results postedRegistry data

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

NCTNCT01297062Other idBCB112

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Overview

Status: Completed
Phase: Phase 1
Enrollment: 94 participants (actual)
Sponsor: AstraZeneca · Industry
Design: Randomized · Triple masking
Countries: 1 country
United States
Start: Feb 2011
Primary completion: Apr 2011
Completion: May 2011
First posted: 16 Feb 2011 (estimated)
Last update posted: 14 Apr 2015 (estimated)
Conditions: Healthy Subjects

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

20112012

Ph 1
A Safety Study to Assess the Effects of Therapeutic and Supratherapeutic Exenatide Concentrations on QT Interval in Healthy Subjects
NCT01297062
Feb 2011 to May 2011

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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

Interventions

ExenatideDrug
MoxifloxacinDrug
Placebo comparatorDrug

Arms3

Experimental
Exenatide
Placebo comparator
Placebo
Active comparator
Moxifloxacin

Primary outcomes3

Outcomes the sponsor listed as primary.

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
Registry description
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
Registry description
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
Registry description
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.

Secondary outcomes(6)

Assay Sensitivity of Moxifloxacin at 1000h (1 Hour Post-administration of Moxifloxacin) on Day 2
Time frame · Baseline, Day 2
Registry description
Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo.
Assay Sensitivity of Moxifloxacin at 1100h (2 Hour Post-administration of Moxifloxacin) on Day 2
Time frame · Baseline, Day 2
Registry description
Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo.
Assay Sensitivity of Moxifloxacin at 1200h (3 Hour Post-administration of Moxifloxacin) on Day 2
Time frame · Baseline, Day 2
Registry description
Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo.
Number of Subjects With QTcP Interval >450msec at Any Timepoint on Any Day in Exenatide and Placebo
Time frame · Day 1, 2, or 3
Registry description
Number of subjects with QTcP \> 450 msec at any timepoint on any day was summarized by frequency for exenatide and placebo.
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
Registry description
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.
Plasma Exenatide Concentrations at Steady State on Day 1, 2 and 3
Time frame · Baseline, Day 1, 2, and 3
Registry description
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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline, Day 1

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)

Group	Value (msec)	Spread
Exenatide	-2.25	0.636
Placebo	-0.89	0.599

Primary outcomeLeast squares mean· Baseline, Day 2

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)

Group	Value (msec)	Spread
Exenatide	-2.58	0.640
Placebo	-0.56	0.596

Primary outcomeLeast squares mean· Baseline, Day 3

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)

Group	Value (msec)	Spread
Exenatide	-3.54	0.675
Placebo	-2.41	0.623

Secondary and other outcome results(5)

Secondary outcomeLeast squares mean· Baseline, Day 2

Assay Sensitivity of Moxifloxacin at 1000h (1 Hour Post-administration of Moxifloxacin) on Day 2

Group	Value (msec)	Spread
Moxifloxacin	1.91	1.079
Placebo	-3.56	0.953

Secondary outcomeLeast squares mean· Baseline, Day 2

Assay Sensitivity of Moxifloxacin at 1100h (2 Hour Post-administration of Moxifloxacin) on Day 2

Group	Value (msec)	Spread
Moxifloxacin	9.75	0.934
Placebo	-0.81	0.872

Secondary outcomeLeast squares mean· Baseline, Day 2

Assay Sensitivity of Moxifloxacin at 1200h (3 Hour Post-administration of Moxifloxacin) on Day 2

Group	Value (msec)	Spread
Moxifloxacin	12.47	1.011
Placebo	1.56	0.828

Secondary outcomeNumber· Day 1, 2, or 3

Number of Subjects With QTcP Interval >450msec at Any Timepoint on Any Day in Exenatide and Placebo

Group	Value (participants)
Exenatide	0
Placebo	0

Secondary outcomeNumber· Baseline, 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

Group	Value (particpants)
Exenatide	0
Placebo	0

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
ExenatideExenatide	–	0 / 80	65 / 80
PlaceboPlacebo Comparator	–	0 / 84	10 / 84
MoxifloxacinMoxifloxacin with placebo infusion	–	1 / 80	8 / 80

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years up to 65 Years
Healthy volunteers: Accepted

Inclusion and exclusion criteria, as posted

Inclusion Criteria: * 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 Exclusion Criteria: * 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

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