NCT03258515

A Study to Investigate the Effect of Single Dose of AZD6094 (600 mg) on Cardiac Repolarization in Healthy Volunteers

A Single-center, Randomized, Double-blind, Placebo-controlled, Three-way Crossover Phase I Study to Investigate the Effect on the QTc Interval of a Single Dose of AZD6094 (600 mg) Compared With Placebo, Using Open-label Moxifloxacin (Avelox®) as a Positive Control, in Healthy Volunteers

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 45 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: Male
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This is a randomized, placebo-controlled, double-blind, 3-way crossover phase I study being conducted on healthy volunteers to investigate the effect of single dose of AZD6094 (600 mg) on cardiac repolarization under well-controlled conditions in accordance with the International Council for Harmonization (ICH) E14 guidelines. An open-label Moxifloxacin (400 mg), a fluoroquinolone broad spectrum antibiotic will be used as a appositive control for the time between the start of the Q wave and the end of the T wave (QT) prolongation in accordance with ICH E14 guidelines, to establish assay sensitivity. The core study consists of screening period, 3 treatment period (AZD6094, placebo and moxifloxacin; with a minimum washout period of 14 days between each treatment period) and follow-up. The study drugs will be administered orally. The study is planned to determine effect of AZD6094 at therapeutic dose, safety and tolerability. This study provides adequate and well-controlled mechanisms to deal with potential bias, facilitate identification of effects related to investigational product (IMP) administration and tolerability issues.

Detailed description

The study is planned to include approximately 45 healthy non-Japanese vasectomized male participants aged 18 to 55 years (inclusive) or male participants over 40 (and up to 55) years old not intending to father children will be enrolled. The study consists of 5 visits comprised of 3 treatment periods with 6 treatment sequences and will have a minimum washout period of 14 days between each treatment period. Visit 1: Screening period (28 days) - Assessments done on Day -1 of treatment period 1. Visits 2 to 4: 3 Treatment periods - Participants will be resident form day before IMP (single oral dose of AZD6094 (600 mg) tablet/AZD6094 matching placebo/moxifloxacin (400 mg) capsule) dosing (Day -1) until at least 48 hours post-dose and will be discharged on Day 3. Visit 5: Follow-up - Participants will have clinical visit 14 days after discharge from the treatment period 3. Participants will be randomized to 6 treatment sequences (ABC, ACB, BAC, BCA, CAB and CBA). In each sequence, participants will receive single oral dose of all 3 treatments (A - AZD6094 600 mg (3X 200 mg tablet), B - Placebo tablet, C - Moxifloxacin 400 mg capsule) with a washout period (14 days) between each treatment period. The study duration will be approximately 84 days.

Conditions

• Solid Tumors

Interventions

Type	Name	Description
DRUG	AZD6094 200 mg	A potent and selective small molecule mesenchymal epithelial transition (MET) kinase inhibitor with significant antitumor activity.
OTHER	Placebo	AZD6094 matching placebo without any pharmacological activity.
DRUG	Moxifloxacin	A fluoroquinolone broad-spectrum antibiotic, produces a mild, but reproducible increase in QT interval corrected (QTc) in healthy normal participants at time to reach maximum concentration (tmax - approximately 2 hours (0.5 to 4 hours)). This effect is close to the ECG interval measured from the onset of the QRS complex (onset of the QRS complex to the J point) to the offset of the T wave (QT)/QTc effect that represents the threshold of regulatory concern, around 5 ms mean QTc interval prolongation.

Timeline

• Start date: 2017-09-06
• Primary completion: 2018-03-24
• Completion: 2018-03-24
• First posted: 2017-08-23
• Last updated: 2020-02-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study