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| Name | Class |
|---|---|
| Eli Lilly and Company | INDUSTRY |
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Compare the effect of exenatide (therapeutic and supratherapeutic concentrations), moxifloxacin and placebo on the QT interval.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Exenatide | Experimental |
| |
| Placebo | Placebo Comparator |
| |
| Moxifloxacin | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exenatide | Drug | IV Exenatide (therapeutic and supratherapeutic concentrations) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | Baseline, Day 3 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, Day 2 |
| Assay Sensitivity of Moxifloxacin at 1100h (2 Hour Post-administration of Moxifloxacin) on Day 2 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vice President Research and Development, MD | Amylin Pharmaceuticals, LLC. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Daytona Beach | Florida | United States | |||
| Research Site |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Moxifloxacin |
| Drug |
Oral Moxifloxacin (400 mg) |
|
| Placebo comparator | Drug | IV Placebo (matching volume of placebo) |
|
Change from baseline in QTcP was analyzed by a MMRM between moxifloxacin and placebo. |
| 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. | 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. | 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. | 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. | Baseline, Day 1, 2, and 3 |
| Evansville |
| Indiana |
| United States |
| FG001 | 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 |
| FG002 | 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 |
| FG003 | 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 |
| FG004 | 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 |
| FG005 | 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 |
| FG006 | Non-Randomized | Not Randomized |
| Intent to Treat (ITT) |
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| Evaluable Population |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo-Exenatide-Moxifloxacin Sequence | Placebo comparator in Period I; Exenatide in Period II; Moxifloxacin with placebo infusion in Period III |
| BG001 | Exenatide-Moxifloxacin-Placebo Sequence | Exenatide in Period I; Moxifloxacin with placebo infusion in Period II; Placebo comparator in Period III |
| BG002 | Moxifloxacin-Placebo-Exenatide Sequence | Moxifloxacin with placebo infusion in Period I; Placebo comparator in Period II; Exenatide in Period III |
| BG003 | Moxifloxacin-Exenatide-Placebo Sequence | Moxifloxacin with placebo infusion in Period I; Exenatide in Period II; Placebo comparator in Period III |
| BG004 | Placebo-Moxifloxacin-Exenatiden Sequence | Placebo comparator in Period I; Moxifloxacin with placebo infusion in Period II; Exenatide in Period III |
| BG005 | Exenatide-Placebo-Moxifloxacin Sequence | Exenatide in Period I; Placebo comparator in Period II; Moxifloxacin with placebo infusion in Period III |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Weight | Mean | Standard Deviation | kilogram |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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) | 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. | 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. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Baseline, Day 1 |
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| Primary | 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. | Evaluable Population. No imputation for missing value was used. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Baseline, Day 2 |
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| Primary | 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. | Evaluable Population. No imputation for missing value was used. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Baseline, Day 3 |
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| Secondary | 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. | Evaluable Population. No imputation for missing value was used. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Baseline, Day 2 |
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| Secondary | 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. | Evaluable Population. No imputation for missing value was used. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Baseline, Day 2 |
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| Secondary | 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. | Evaluable Population. No imputation for missing value was used. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Baseline, Day 2 |
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| Secondary | 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. | Evaluable Population. No imputation for missing value was used. | Posted | Number | participants | Day 1, 2, or 3 |
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| Secondary | 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. | Evaluable Population. No imputation for missing value was used. | Posted | Number | particpants | Baseline, Day 1, 2, or 3 |
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| Secondary | 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. | Evaluable Population. No imputation for missing value was used. Day 1, 2, and 3 exenatide concentration < LLOQ was set to missing. | Posted | Geometric Mean | Standard Error | pg/mL | Baseline, Day 1, 2, and 3 |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Exenatide | Exenatide | 0 | 80 | 65 | 80 | ||
| EG001 | Placebo | Placebo Comparator | 0 | 84 | 10 | 84 | ||
| EG002 | Moxifloxacin | Moxifloxacin with placebo infusion | 1 | 80 | 8 | 80 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| BLOOD CREATINE PHOSPHOKINASE INCREASED | Investigations | MedDRA 13.1 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| NAUSEA | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
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| VOMITING | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
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| GASTROOESOPHAGEAL REFLUX DISEASE | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
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| DECREASED APPETITE | Metabolism and nutrition disorders | MedDRA 13.1 | Non-systematic Assessment |
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| DYSPEPSIA | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
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| ABDOMINAL DISTENSION | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
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| CONSTIPATION | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
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| DYSGEUSIA | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
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| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
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| DIZZINESS | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
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| DERMATITIS CONTACT | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
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| DIARRHOEA | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
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| EARLY SATIETY | General disorders | MedDRA 13.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Peter Ohman, Medical Science Director | AstraZeneca | ClinicalTrialTransparency@astrazeneca.com |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000077270 | Exenatide |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014688 | Venoms |
| D045424 | Complex Mixtures |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Male |
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Non-inferiority is established if the upper limit of 2-sided 90% confidence interval (CI), equivalent to the upper limit of 1-sided 95% CI, for change from baseline in QTcP (exenatide - placebo) is below 10 msec. |
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