4-way Crossover QT Evaluation in Healthy Subjects

NCT03709927 | Completed Phase 1 FDA Drug

• 1 other identifier: ZTI-01-101
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate if ZTI-01 (fosfomycin for injection), an investigational drug being developed to treat people with complicated urinary tract and kidney infections, has any effect on the electrical activity of the heart.

Conditions

Cardiac Repolarization in Healthy Subjects

Outcome Measures

Primary Outcomes (1)

• Effect of ZTI-01 at the therapeutic and supra-therapeutic plasma concentration on cardiac repolarization expressed by QT interval

  Determine the change-from-baseline QTc (ΔQTc) when compared with placebo, and moxifloxacin (400 mg PO)

  24 hour Holter ECG at Baseline (Day -1) & day of dosing (Day 1) in each of 4 periods. 10 replicates per time point at 13 timepoints: pre-dose: 60, 45 and 30 minutes; after the start of infusion: 0.5, 1 (end infusion), 1.25, 1.5, 2, 3, 4, 8, 12, & 24 hrs

Secondary Outcomes (1)

• Treatment emergent adverse events (TEAEs)

  From Day 1 start of dosing up to Day 36-38 (final follow up visit)

Other Outcomes (1)

• Cmax after a single dose IV administration of ZTI-01 6g and 12g

  Cmax at end of 1-hour single dose infusion

Study Arms (4)

Therapeutic ZTI-01 6 g IV

EXPERIMENTAL

intravenous fosfomycin (only antibiotic in phosphonic acid derivative class) 6g

Drug: ZTI-01

Supra-therapeutic ZTI-01 12 g IV

EXPERIMENTAL

intravenous fosfomycin (only antibiotic in phosphonic acid derivative class) 12g

Drug: ZTI-01

moxifloxacin 400 mg PO

ACTIVE COMPARATOR

oral moxifloxacin 400mg film coated tablets - Avelox(TM)

Drug: Moxifloxacin 400mg; Other: Placebo IV

Placebo IV

PLACEBO COMPARATOR

IV 0.9% normal saline solution

Other: Placebo IV

Interventions

ZTI-01 DRUG

6g IV fosfomycin

Also known as: IV fosfomycin, fosfomycin disodium, fosfomycin for injection

Supra-therapeutic ZTI-01 12 g IV; Therapeutic ZTI-01 6 g IV

Moxifloxacin 400mg DRUG

oral moxifloxacin (Avelox 400 mg) + IV normal saline (Placebo)

Also known as: Positive control

moxifloxacin 400 mg PO

Placebo IV OTHER

IV Placebo (0.9% Normal Saline)

Also known as: Negative Control

Placebo IV; moxifloxacin 400 mg PO

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• physically and mentally healthy volunteer
• a man or woman, 18 to 55 years of age
• a woman of childbearing potential using birth control / negative pregnancy test or a woman of non-childbearing potential
• males with female partners of childbearing potential agree to use contraception
• body mass index 19.0 to 32.0 kg/m2; weight of at least 60.0 kg at Screening
• willing to complete the required 4 study periods

You may not qualify if:

• History or evidence of cerebrovascular or cardiac disease
• Uncontrolled hypertension
• Electrographically significant abnormalities on ECG
• Clinically significant medical history (PI assessment)
• Clinically relevant lab abnormalities (PI assessment)
• Calculated eGFR \< 60.0 mL/min/1.73m2 based on CKD-EPI 2009 equation
• Abnormal liver tests
• Positive serology HIV, HBsAg, or Hep C virus
• Hemoglobin, hematocrit, electrolytes below lower limit of normal
• Received any hepatic or renal clearance altering agents within 30 days
• History of allergy or hypersensitivity to drugs with clinically significant reaction
• Unwilling to refrain from strenuous exercise from 7 days prior to admission until discharge
• Uses any prescription drug / OTC, within 7 days prior to admission, or 14 days prior to Admission if the drug is a potential inducer or inhibitor of cP450, or 5 half-lives (if longer), or subject continued use of a prescription drug / OTC medication (except contraceptives)
• Scheduled to have surgical procedure during study
• Acute illness that has resolved in less than 14 days, or has had a major illness, or hospitalization within 1 month

Sponsors & Collaborators

• Nabriva Therapeutics AG: lead

Study Sites (1)

Pharmaron

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Interventions

Fosfomycin; Injections; Moxifloxacin

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Drug Administration Routes; Drug Therapy; Therapeutics; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Evelyn J Ellis-Grosse, PhD

  Chief Scientific Officer

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Single dose study treatments will be administered in blinded, randomized sequence in separate periods with each subject in the study exposed to each of the four treatments.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 4-way cross over (two doses of ZTI-01, placebo and oral moxifloxacin)

Study Record Dates

• First Submitted: May 8, 2018
• First Posted: October 17, 2018
• Study Start: January 11, 2018
• Primary Completion: April 12, 2018
• Study Completion: August 21, 2018
• Last Updated: March 6, 2019

Record last verified: 2019-03

Locations

US (1)