4-way Crossover QT Evaluation in Healthy Subjects

Cardiac Repolarization in Healthy Subjects Clinical Trial

Official title:

A Phase 1, Randomized, Blinded, Placebo and Moxifloxacin Controlled, 4-Period Crossover, Study Evaluating the Effect of ZTI-01 on 12-Lead Electrocardiogram Parameters in Healthy Adult Subject

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03709927
• Other study ID #: ZTI-01-101
• Status: Completed
• Phase: Phase 1
• Start date: January 11, 2018
• Est. completion date: August 21, 2018

Study information

• Verified date: March 2019
• Source: Nabriva Therapeutics AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: August 21, 2018
• Est. primary completion date: April 12, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cardiac Repolarization in Healthy Subjects

Intervention

Drug:
• ZTI-01
6g IV fosfomycin
• Moxifloxacin 400mg
oral moxifloxacin (Avelox 400 mg) + IV normal saline (Placebo)

Other:
• Placebo IV
IV Placebo (0.9% Normal Saline)

Locations

Country	Name	City	State
United States	Pharmaron	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Nabriva Therapeutics AG

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cmax after a single dose IV administration of ZTI-01 6g and 12g	Maximum plasma concentration Cmax (microg/mL) by dose (6g and 12g)	Cmax at end of 1-hour single dose infusion
Primary	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 (?QTc) 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	Treatment emergent adverse events (TEAEs)	Number and percentage of subjects reporting a TEAE overall and by treatment	From Day 1 start of dosing up to Day 36-38 (final follow up visit)