A Study to Investigate the Effect of Single Dose of AZD6094 (600 mg) on Cardiac Repolarization in Healthy Volunteers
Condition: Solid Tumors
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): AZD6094 200 mg; Placebo; Moxifloxacin
Intervention type(s): Drug; Other; Drug
Intervention description(s): A potent and selective small molecule mesenchymal epithelial transition (MET) kinase inhibitor with significant antitumor activity.; AZD6094 matching placebo without any pharmacological activity.; 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.
Other intervention name(s): Avelox
Intervention MeSH terms: Moxifloxacin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Mesenchymal epithelial transition (MET) receptor; Small molecule kinase inhibitors; Moxifloxacin (Avelox); QT prolongation