A Thorough QTc Evaluation of the Effect of Semaglutide on Cardiac Repolarisation in Healthy Subjects

A Thorough QTc Evaluation of the Effect of Semaglutide on Cardiac Repolarisation in Healthy Subjects: A Randomised, Double-Blind,Placebo-Controlled, Three-Arm Parallel Trial With a Nested Cross-Over Design for Positive Control With Moxifloxacin Administration

This trial is conducted in Europe. The aim of the trial is to evaluate the effect of semaglutide on cardiac repolarisation in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy; Diabetes
• Intervention / Treatment: Drug: semaglutide; Drug: placebo; Drug: moxifloxacin

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI (Body Mass Index): 20-30 kg/m^2
• Body weight: 60-110 kg
• Normal ECG (electrocardiogram)

Exclusion Criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method. Women of child-bearing potential must use an effective method of birth control for the duration of the trial and for 5 weeks following the last dose of semaglutide. Only highly effective methods of birth control are accepted (i.e. one that results in less than 1% per year failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices), or sexual abstinence or vasectomised partner
• Any clinically significant disease history, in the opinion of the investigator, or systemic or organ
• History of seizures, epilepsy, syncope, cardiac arrest, cardiac arrhythmia or Torsades de Pointes, A-V (Atrioventricular) block or structural heart disease
• Family history of long QT (Interval in the ECG: from the start of the QRS complex to the end) syndrome (either objectively diagnosed or suggested by sudden death due to cardiac causes before the age of 50 of a 1st degree relative)
• Family history of sudden cardiac death before the age of 50 of a 1st degree relative
• Use of prescription or non-prescription systemic or topical medicinal products (except routine vitamins, acetylsalicylic acid, paracetamol and contraceptives) within 3 weeks (or within 5 halflives of the medicinal product, whichever is longest) prior to the first dosing of semaglutide
• Smoking, drug or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: semaglutide + moxifloxacin placebo; Subjects will receive a single dose of moxifloxacin placebo both before the start of semaglutide treatment and at the end of the semaglutide treatment.	Drug: semaglutide; Solution for subcutaneous (s.c., under the skin) injection. Dose escalation to 1.5 mg.; Drug: placebo; Solution for s.c. injection or tablets for oral administration
Active Comparator: Arm 2A: Semaglutide placebo + moxifloxacin/moxifloxacin placebo: Subjects will receive moxifloxacin before the start of semaglutide placebo treatment and moxifloxacin placebo at the end of the semaglutide placebo treatment.	Drug: placebo; Solution for s.c. injection or tablets for oral administration; Drug: moxifloxacin; Tablets for oral administration
Experimental: Arm 2B: Semaglutide placebo + moxifloxacin placebo/moxifloxacin: Subjects will receive moxifloxacin placebo before the start of semaglutide placebo treatment and moxifloxacin at the end of the semaglutide placebo treatment.	Drug: placebo; Solution for s.c. injection or tablets for oral administration; Drug: moxifloxacin; Tablets for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
QTcI, (Individual heart rate corrected QT (Interval in the ECG: from the start of the QRS complex to the end) interval) based on ECG recordings obtained at 11 time points	0-48 hours after the fourth dose of semaglutide/semaglutide placebo at the 1.5 mg dose level

Secondary Outcome Measures

Outcome Measure	Time Frame
QTcI, based on ECG (electrocardiogram) recordings obtained at 2 out of 8 time points	0-24 hours after a single dose of moxifloxacin/moxifloxacin placebo

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Demmel V, Sandberg-Schaal A, Jacobsen JB, Golor G, Pettersson J, Flint A. No QTc Prolongation with Semaglutide: A Thorough QT Study in Healthy Subjects. Diabetes Ther. 2018 Aug;9(4):1441-1456. doi: 10.1007/s13300-018-0442-0. Epub 2018 May 24.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2014
• Primary Completion (Actual): April 23, 2015
• Study Completion (Actual): April 23, 2015

Study Registration Dates

• First Submitted: February 13, 2014
• First Submitted That Met QC Criteria: February 13, 2014
• First Posted (Estimate): February 17, 2014

Study Record Updates

• Last Update Posted (Actual): June 13, 2018
• Last Update Submitted That Met QC Criteria: June 11, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: NN9535-3652; 2012-005073-31 (EudraCT Number); U1111-1136-6455 (Other Identifier: WHO)