Study of the Effects of Intravenous Exenatide on Cardiac Repolarization

NCT02650479 | Completed Phase 1

• 1 other identifier: ITCA-650-CLP-114
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

Two-Part, Randomized, Placebo and Active-Controlled, Double-Blind, Thorough QT Study Evaluating the Effects of Intravenous Exenatide on Cardiac Repolarization in Healthy Male and Female Volunteers

Conditions

Healthy Adult Male and Female Volunteers

Outcome Measures

Primary Outcomes (2)

• Pilot Study: Establishment of mean plasma steady state concentration of 500 pg/mL

  35 days

• Core Study: Changes to QTc interval changes (threshold > 10 msec) measurements

  56 days

Secondary Outcomes (15)

• Pilot Study: Adverse events as assessed by subjective subject reporting, laboratory testing, ECG, physical examinations, and vital signs

  35 days

• Core Study: Measurement of exenatide plasma concentrations and relationship to changes in QTc interval measurements

  56 days

• Core Study: Changes in PR, RR, QRS, QT, T- and U- wave morphology

  56 days

• Core Study: Measurement of QTc interval changes moxifloxacin as active control

  56 days

• Core Study: Adverse events as assessed by subjective subject reporting, laboratory testing, ECG, physical examinations, and vital signs

  56 days

Study Arms (4)

IV exenatide - pilot study

OTHER

IV Exenatide Infusion 0.1250 mcg/kg/hour for 0.5 hours followed by 0.0625 mcg/kg/hour for 5.5 hours, preceded by IV Palonosetron 0.25 mg for nausea/vomiting prophylaxis.

Drug: Exenatide; Drug: Palonosetron

Treatment Group A - core study

EXPERIMENTAL

IV Exenatide Infusion 0.1250 mcg/kg/hour for 0.5 hours followed by 0.0625 mcg/kg/hour for 5.5 hours, preceded by IV Palonosetron 0.25 mg for nausea/vomiting prophylaxis.

Drug: Exenatide; Drug: Palonosetron

Treatment Group B - core study

EXPERIMENTAL

IV infusion of placebo over 6 hours, preceded by IV Palonosetron 0.25 mg for nausea/vomiting prophylaxis.

Drug: Placebo; Drug: Palonosetron

Treatment Group C - core study

EXPERIMENTAL

IV infusion of placebo over 6 hours and a single oral dose of 400 mg moxifloxacin within 1 min of start of infusion, preceded by IV Palonosetron 0.25 mg for nausea/vomiting prophylaxis.

Drug: Placebo; Drug: Moxifloxacin; Drug: Palonosetron

Interventions

Exenatide DRUG

6 hour IV infusion (double infusion of 0.1250 mcg/kg/hour for 30 min followed by infusion rate (1X) of 0.0625 mcg/kg/hour for 5.5 hours).

IV exenatide - pilot study; Treatment Group A - core study

Placebo DRUG

6 hour IV infusion.

Treatment Group B - core study; Treatment Group C - core study

Moxifloxacin DRUG

400 mg oral dose moxifloxacin within 1 min of start of infusion of exenatide

Treatment Group C - core study

Palonosetron DRUG

0.25 mg administered IV within 30 minutes prior to initiating the infusion of exenatide

IV exenatide - pilot study; Treatment Group A - core study; Treatment Group B - core study; Treatment Group C - core study

Eligibility Criteria

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

You may qualify if:

• Body mass index (BMI) between 19 to 35 kg/m2 inclusive.
• Women of child bearing potential - use of an additional adequate method of contraception during the study and until 1 additional menstrual cycle following the end-of-study (EOS) visit. Adequate methods of contraception for women of child bearing potential (WOCBP) include: mechanical products (ie, intrauterine device \[IUD\]-copper IUD); or barrier methods (eg, diaphragm, condoms, cervical cap) with spermacide.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and bilirubin within normal range at Screening.
• Fasting triglycerides within the normal range at Screening

You may not qualify if:

• History of type 1 or type 2 diabetes, or history of hypoglycemia.
• History or evidence of myocardial infarction, congestive heart failure, syncope not related to heart arrhythmia, coronary revascularization (coronary artery bypass grafting or percutaneous coronary intervention), unstable angina, or cerebrovascular accident or stroke or TIA.
• History of atrial fibrillation, flutter, or non-sustained or sustained VT.
• Personal or family history of sudden death or long QT syndrome.
• History of uncontrolled hypertension.
• History or evidence of acute or chronic pancreatitis.
• History of liver disease.
• Abnormal renal function.
• History of medullary thyroid cancer or a personal or family history of multiple endocrine neoplasia type 2.
• Thyroid-stimulating hormone (TSH) outside of normal limits at Screening .
• Weight loss surgery.
• History of malignancy (not including basal or squamous cell carcinoma of the skin with past 5 years). (Subjects who have been disease free for greater than 5 years may be included.)
• History of active alcohol within 1 year prior to Screening.
• History of drug abuse within 5 years prior to Screening or a positive prestudy drug screen.
• Weekly consumption of more than 14 alcoholic beverages for females and more than 21 alcoholic beverages for males.

Sponsors & Collaborators

• Intarcia Therapeutics: lead

Study Sites (1)

PRA-Groningen

Groningen, Netherlands

Location

MeSH Terms

Interventions

Exenatide; Moxifloxacin; Palonosetron

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; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Isoquinolines

Study Design

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

Study Record Dates

• First Submitted: January 1, 2016
• First Posted: January 8, 2016
• Study Start: January 1, 2016
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: January 27, 2017

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)