4-way Crossover QT Evaluation in Healthy Subjects

NCT ID: NCT03709927

Last Updated: 2019-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-11
• Study Completion Date: 2018-08-21

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.

Detailed Description

This is a single-center, randomized, placebo-controlled, four-period, cross-over study to assess the effect of single-doses of ZTI-01 at therapeutic (T) and supratherapeutic (ST) plasma concentrations on the QTc interval versus placebo (P) and an open-label moxifloxacin (M) control (400 mg PO).

Assessment of safety data will include changes from baseline in vital signs and laboratory parameters, infusion site reactions, adverse events and clinically significant changes from baseline in 12-lead ECG parameters.

Conditions

Cardiac Repolarization in Healthy Subjects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Therapeutic ZTI-01 6 g IV

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

Group Type: EXPERIMENTAL

ZTI-01

Intervention Type: DRUG

6g IV fosfomycin

Supra-therapeutic ZTI-01 12 g IV

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

Group Type: EXPERIMENTAL

ZTI-01

Intervention Type: DRUG

6g IV fosfomycin

moxifloxacin 400 mg PO

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

Group Type: ACTIVE_COMPARATOR

Moxifloxacin 400mg

Intervention Type: DRUG

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

Placebo IV

Intervention Type: OTHER

IV Placebo (0.9% Normal Saline)

Placebo IV

IV 0.9% normal saline solution

Group Type: PLACEBO_COMPARATOR

Placebo IV

Intervention Type: OTHER

IV Placebo (0.9% Normal Saline)

Interventions

ZTI-01

6g IV fosfomycin

Intervention Type: DRUG

Moxifloxacin 400mg

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

Intervention Type: DRUG

Placebo IV

IV Placebo (0.9% Normal Saline)

Intervention Type: OTHER

Other Intervention Names

IV fosfomycin; fosfomycin disodium; fosfomycin for injection; Positive control; Negative Control

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Unwilling to abstain from ingestion of caffeine or xanthine-containing products 96 hours prior and throughout study
• Unwilling to abstain from alcohol beginning 72 hours prior and throughout study
• History of high alcohol consumption within 6 months
• History of drug abuse (in the previous 3 years) or positive urine drug screen
• Used tobacco-containing products within 6 months or has a positive cotinine
• Consumed grapefruit and/or grapefruit juice within 14 days and throughout study
• Consumed other fruit juices within 72 hours and throughout study
• Consumed cruciferous vegetables or charbroiled meats within 7 days and throughout study
• Donated plasma or blood within 30 days or has a history of blood donation of > 450 mL within 3 months
• Used any investigational drug within 30 days
• Previously received fosfomycin
• Deemed by the Investigator to be inappropriate for this study
• Participated in another clinical study within 30 days (or 5 half-lives)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Nabriva Therapeutics AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Evelyn J Ellis-Grosse, PhD

Role: STUDY_CHAIR

Chief Scientific Officer

Locations

Pharmaron

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

ZTI-01-101

Identifier Type: -

Identifier Source: org_study_id