Trial Outcomes & Findings for A Safety Study to Assess the Effects of Therapeutic and Supratherapeutic Exenatide Concentrations on QT Interval in Healthy Subjects (NCT NCT01297062)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

94 participants

Primary outcome timeframe

Baseline, Day 1

Results posted on

2015-04-14

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo-Exenatide-Moxifloxacin Sequence Placebo comparator in Period I; Exenatide in Period II; Moxifloxacin with placebo infusion in Period III; Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3) Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2 Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3	Exenatide-Moxifloxacin-Placebo Sequence Exenatide in Period I; Moxifloxacin with placebo infusion in Period II; Placebo comparator in Period III Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3) Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2 Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3	Moxifloxacin-Placebo-Exenatide Sequence Moxifloxacin with placebo infusion in Period I; Placebo comparator in Period II; Exenatide in Period III Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3) Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2 Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3	Moxifloxacin-Exenatide-Placebo Sequence Moxifloxacin with placebo infusion in Period I; Exenatide in Period II; Placebo comparator in Period III Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3) Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2 Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3	Placebo-Moxifloxacin-Exenatiden Sequence Placebo comparator in Period I; Moxifloxacin with placebo infusion in Period II; Exenatide in Period III Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3) Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2 Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3	Exenatide-Placebo-Moxifloxacin Sequence Exenatide in Period I; Placebo comparator in Period II; Moxifloxacin with placebo infusion in Period III Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3) Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2 Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3	Non-Randomized Not Randomized
Overall Study STARTED	15	14	14	14	15	14	8
Overall Study Intent to Treat (ITT)	15	14	14	14	15	14	0
Overall Study Evaluable Population	11	12	12	13	13	13	0
Overall Study COMPLETED	11	13	12	13	13	13	0
Overall Study NOT COMPLETED	4	1	2	1	2	1	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo-Exenatide-Moxifloxacin Sequence Placebo comparator in Period I; Exenatide in Period II; Moxifloxacin with placebo infusion in Period III; Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3) Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2 Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3	Exenatide-Moxifloxacin-Placebo Sequence Exenatide in Period I; Moxifloxacin with placebo infusion in Period II; Placebo comparator in Period III Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3) Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2 Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3	Moxifloxacin-Placebo-Exenatide Sequence Moxifloxacin with placebo infusion in Period I; Placebo comparator in Period II; Exenatide in Period III Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3) Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2 Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3	Moxifloxacin-Exenatide-Placebo Sequence Moxifloxacin with placebo infusion in Period I; Exenatide in Period II; Placebo comparator in Period III Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3) Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2 Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3	Placebo-Moxifloxacin-Exenatiden Sequence Placebo comparator in Period I; Moxifloxacin with placebo infusion in Period II; Exenatide in Period III Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3) Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2 Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3	Exenatide-Placebo-Moxifloxacin Sequence Exenatide in Period I; Placebo comparator in Period II; Moxifloxacin with placebo infusion in Period III Exenatide - stepped intravenous (IV) infusion to gradually deliver levels of exenatide at concentrations of approximately 200 pg/mL (Day 1), 300 pg/mL (Day 2), and 500 pg/mL (Day 3) Moxifloxacin - Placebo intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) with single oral dose of Moxifloxacin (400 mg) on Day 2 Placebo - intravenously infused at the same volume rate (mL/min) as that of active study medication (exenatide) on Day 1, Day 2, and Day 3	Non-Randomized Not Randomized
Overall Study Adverse Event	2	0	1	0	0	0	0
Overall Study Physician Decision	1	0	1	0	0	0	6
Overall Study Protocol Violation	0	0	0	0	1	0	0
Overall Study Subject Decision	1	1	0	1	1	1	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo-Exenatide-Moxifloxacin Sequence n=15 Participants Placebo comparator in Period I; Exenatide in Period II; Moxifloxacin with placebo infusion in Period III	Exenatide-Moxifloxacin-Placebo Sequence n=14 Participants Exenatide in Period I; Moxifloxacin with placebo infusion in Period II; Placebo comparator in Period III	Moxifloxacin-Placebo-Exenatide Sequence n=14 Participants Moxifloxacin with placebo infusion in Period I; Placebo comparator in Period II; Exenatide in Period III	Moxifloxacin-Exenatide-Placebo Sequence n=14 Participants Moxifloxacin with placebo infusion in Period I; Exenatide in Period II; Placebo comparator in Period III	Placebo-Moxifloxacin-Exenatiden Sequence n=15 Participants Placebo comparator in Period I; Moxifloxacin with placebo infusion in Period II; Exenatide in Period III	Exenatide-Placebo-Moxifloxacin Sequence n=14 Participants Exenatide in Period I; Placebo comparator in Period II; Moxifloxacin with placebo infusion in Period III	Total n=86 Participants Total of all reporting groups
Age, Continuous	41.5 years STANDARD_DEVIATION 8.98 • n=5 Participants	45.1 years STANDARD_DEVIATION 11.43 • n=7 Participants	43.7 years STANDARD_DEVIATION 11.56 • n=5 Participants	37.8 years STANDARD_DEVIATION 10.66 • n=4 Participants	43.3 years STANDARD_DEVIATION 13.74 • n=21 Participants	41.0 years STANDARD_DEVIATION 10.50 • n=8 Participants	42.1 years STANDARD_DEVIATION 11.16 • n=8 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=8 Participants	8 Participants n=8 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	12 Participants n=7 Participants	11 Participants n=5 Participants	14 Participants n=4 Participants	13 Participants n=21 Participants	13 Participants n=8 Participants	78 Participants n=8 Participants
Weight	87.66 kilogram STANDARD_DEVIATION 8.107 • n=5 Participants	81.16 kilogram STANDARD_DEVIATION 11.235 • n=7 Participants	90.77 kilogram STANDARD_DEVIATION 12.375 • n=5 Participants	93.66 kilogram STANDARD_DEVIATION 11.704 • n=4 Participants	89.71 kilogram STANDARD_DEVIATION 7.726 • n=21 Participants	90.71 kilogram STANDARD_DEVIATION 11.251 • n=8 Participants	88.94 kilogram STANDARD_DEVIATION 10.899 • n=8 Participants

PRIMARY outcome

Timeframe: Baseline, Day 1

Population: 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.

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.