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

NCT01297062 | Completed Phase 1 Results

• 1 other identifier: BCB112
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Healthy Subjects

Keywords

Diabetes; exenatide; Amylin; Lilly; QT interval

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (6)

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

  Baseline, Day 2

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

  Baseline, Day 2

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

  Baseline, Day 2

• Number of Subjects With QTcP Interval >450msec at Any Timepoint on Any Day in 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

  Baseline, Day 1, 2, or 3

Study Arms (3)

Exenatide

EXPERIMENTAL

Drug: Exenatide

Placebo

PLACEBO COMPARATOR

Drug: Placebo comparator

Moxifloxacin

ACTIVE COMPARATOR

Drug: Moxifloxacin

Interventions

Exenatide DRUG

IV Exenatide (therapeutic and supratherapeutic concentrations)

Exenatide

Moxifloxacin DRUG

Oral Moxifloxacin (400 mg)

Moxifloxacin

Placebo comparator DRUG

IV Placebo (matching volume of placebo)

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Eli Lilly and Company: collaborator

Study Sites (2)

Research Site

Daytona Beach, Florida, United States

Location

Research Site

Evansville, Indiana, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Exenatide; Moxifloxacin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Peter Ohman, Medical Science Director
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Vice President Research and Development, MD

  Amylin Pharmaceuticals, LLC.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2011
• First Posted: February 16, 2011
• Study Start: February 1, 2011
• Primary Completion: April 1, 2011
• Study Completion: May 1, 2011
• Last Updated: April 14, 2015
• Results First Posted: May 31, 2012

Record last verified: 2015-03

Locations

US (2)