A Placebo-controlled Four Way Crossover Study to Asses the Effect of a Single Oral Dose of NKTR-118 on QTc Interval in Healthy Male Subjects

A Single Center, Randomized, Double-blinded, Placebo-controlled, Open-label, Positive-controlled, Four-way Crossover Study to Assess the Effect of a Single Oral Dose NKTR-118 Administration on QTc Interval Compared to Placebo, Using AVELOX (Moxifloxacin) as a Positive Control, in Healthy Male Subjects

The purpose of this study is to evaluate the effects on QTc interval in healthy males when administered a single dose of NKTR-118 compared with placebo and moxifloxacin. (QTc is a specific time interval that can be measured in a heart beat by taking Electrocardiogram (ECG))

Study Overview

• Status: Completed
• Conditions: Amount of NKTR-118 in Blood; Variation in the Heart's Electrical Cycle
• Intervention / Treatment: Drug: Placebo; Drug: NKTR-118; Drug: moxifloxacin

Detailed Description

A Single Center, Randomized, Double-blinded, Placebo-controlled, Open-label, Positive-controlled, Four-way Crossover Study to Assess the Effect of a Single Oral Dose NKTR-118 Administration on QTc Interval Compared to Placebo, Using AVELOX (moxifloxacin) as a Positive Control, in Healthy Male Subjects

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
• Body mass index (BMI) between 18 and 30 kg/m2 (inclusive) and weight at least 50 kg but no more than 100 kg.

Exclusion Criteria:

• Clinically significant medical history including severe allergies or a history of mental disorders or any cardiac history, history or presence of gastrointestinal, hepatic, or renal disease.
• Abnormal heart rhythm including any abnormal arrhythmias, marked sinus arrhythmias, or junctional rhythms.
• Known or suspected history of drug abuse, current smokers or those who have smoked and/or used nicotine products within 3 months prior to enrollment.
• Excessive intake of caffeine-containing products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; NKTR-118 25 mg (1x25 mg tablet + 5x placebo tablets)	Drug: Placebo; tablet; Drug: NKTR-118; 25 mg tablet
Experimental: B; NKTR-118 150 mg (6x25 mg tablet)	Drug: Placebo; tablet; Drug: NKTR-118; 25 mg tablet
Placebo Comparator: C; NKTR-118 placebo (6x placebo tablets)	Drug: Placebo; tablet
Active Comparator: D; Moxifloxacin (1 x 400 mg tablet)	Drug: moxifloxacin; 400 mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the effect of a single dose of NKTR-118 25 mg and 150 mg on the change in time-matched QTcF intervals compared with placebo	30 days pre-dose through 4 treatment periods and follow up 71 days post dose.
The effect of a single dose of NKTR-118 25 mg and 150 mg on the change in time-matched QTcF intervals compared with placebo	Follow up 71 days post dose.

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the effect of a single oral dose of moxifloxacin 400 mg on the changes in time-match QTcF intervals compared with placebo, which will be used as supporting data.	30 days pre-dose through 4 treatment periods
Collect adverse events to assess the safety after dosing of NKTR-118 25mg and 150 mg in healthy male subjects.	30 days pre-dose through 4 treatment periods
To evaluate the effect of a single oral dose of moxifloxacin 400 mg on the changes in time-match QTcF intervals compared with placebo, which will be used as supporting data.	Follow up 71 days post dose
Collect adverse events to assess the safety after dosing of NKTR-118 25mg and 150mg in healthy male subjects.	Follow up 71 days post dose.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: David Matthews, MD, Quintiles, Overland Park Kansas US; Study Chair: Emilie Ramos, MD, AstraZeneca, Alderley Park, UK

Publications and helpful links

General Publications

• Gottfridsson C, Carlson G, Lappalainen J, Sostek M. Evaluation of the effect of Naloxegol on cardiac repolarization: a randomized, placebo- and positive-controlled crossover thorough QT/QTc study in healthy volunteers. Clin Ther. 2013 Dec;35(12):1876-83. doi: 10.1016/j.clinthera.2013.09.019. Epub 2013 Nov 13.

Helpful Links

• D3820C00014 Clinical Study Report Synopsis

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: March 28, 2011
• First Submitted That Met QC Criteria: March 28, 2011
• First Posted (Estimate): March 29, 2011

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 13, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Phase 1; NKTR-118; cross-over study; healthy male volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Narcotic Antagonists; Moxifloxacin; Naloxegol
• Other Study ID Numbers: D3820C00014