NCT03404167

A Study to Evaluate the Safety, Tolerability and Plasma PK of a Single Oral Dose of Zoliflodacin in Healthy Male and Female Volunteers

Completed Phase 1 Results posted Last updated 18 March 2019

What this trial tests

Phase 1 trial testing AZD0914 in Gonorrhoea in 8 participants. Completed in 2 March 2018.

Timeline

2 February 2018

Primary endpoint
2 March 2018

2 March 2018

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	8
Start date	2 February 2018
Primary completion	2 March 2018
Estimated completion	2 March 2018
Sites	1 location across United States

Drugs / interventions tested

• AZD0914 — full drug profile →

Conditions studied

• Gonorrhoea — all drugs for Gonorrhoea →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 18 to 45, any sex, with Gonorrhoea. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Observed Concentration (Cmax) of Zoliflodacin Primary · From Day 1 to Day 4

Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations computed from concentrations that were measured using a validated HPLC-MS/MS method.

Group	Value	95% CI
Zoliflodacin	20863	± 7129

Time of Maximum Observed Concentration (Tmax) of Zoliflodacin Primary · From Day 1 to Day 4

Tmax was defined as the time at which the maximum concentration (Cmax) occurs in plasma computed from concentrations that were measured using a validated HPLC-MS/MS method.

Group	Value	95% CI
Zoliflodacin	4	± 3

Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Zoliflodacin Primary · From Day 1 to Day 4

AUC(0-8) was defined as the total area under the concentration-time curve from dosing (time 0) taken to the limit as the end time becomes arbitrarily large. AUC(0-8) and was calculated by adding AUC(0-last) to an extrapolated value equal to the last measured concentration greater than the lower limit of quantification of the bioanalytical assay divided by the terminal phase elimination rate constant (Ke) computed from concentrations that were measured using a validated HPLC-MS/MS method.

Group	Value	95% CI
Zoliflodacin	226750	± 85336

Area Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin Primary · From Day 1 to Day 4

AUC(0-last) was defined as the area under the concentration-time curve from dosing (time 0) to the time of the last measured concentration computed from concentrations that were measured using a validated HPLC-MS/MS method.

Group	Value	95% CI
Zoliflodacin	226500	± 85340

Apparent Volume of Distribution (Vz/F) of Zoliflodacin Primary · From Day 1 to Day 4

Apparent volume of distribution during terminal phase (Vz/F) after non-intravenous administration was calculated as (CL/F)/ Ke computed from concentrations that were measured using a validated HPLC-MS/MS method.

Group	Value	95% CI
Zoliflodacin	183.6	± 58.8

Apparent Oral Clearance (CL/F) of Zoliflodacin Primary · Day 1 to Day 4

Apparent oral clearance (CL/F) computed as Dose/Area under the curve (AUC) from time zero to infinity (0-8) computed from concentrations that were measured using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method.

Group	Value	95% CI
Zoliflodacin	19.9	± 7.0

Elimination Rate Constant (Ke) of Zoliflodacin Primary · From Day 1 to Day 4

The terminal phase elimination rate constant (Ke) was defined as the first-order rate constant describing the rate of decrease of drug concentration in the terminal phase (defined as the terminal region of the PK curve where drug concentration follows first-order elimination kinetics) computed from concentrations that were measured using a validated HPLC-MS/MS method.

Group	Value	95% CI
Zoliflodacin	0.108	± 0.011

Terminal Elimination Half-life (t1/2) of Zoliflodacin Primary · From Day 1 to Day 4

The apparent terminal elimination half-life (t1/2) was defined as the time required for the drug concentration to decrease by a factor of one-half in the terminal phase computed from concentrations that were measured using a validated HPLC-MS/MS method.

Group	Value	95% CI
Zoliflodacin	6.5	± 0.6

Changes From Baseline for White Blood Cells With Differentials and Platelets Secondary · From Day -1 through Day 4

Change from baseline calculated by subtracting the Day -1 (baseline) hematology measurement from the Day 4 hematology measurement. Hematology parameters included white blood cell count, differential (absolute counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils), and platelet count.

Leukocytes

Group	Value	95% CI
Zoliflodacin	-0.659	± 1.668

Neutrophils

Group	Value	95% CI
Zoliflodacin	-0.118	± 0.950

Lymphocytes

Group	Value	95% CI
Zoliflodacin	-0.465	± 0.689

Monocytes

Group	Value	95% CI
Zoliflodacin	-0.036	± 0.075

Eosinophils

Group	Value	95% CI
Zoliflodacin	-0.035	± 0.096

Basophils

Group	Value	95% CI
Zoliflodacin	-0.008	± 0.019

Platelets

Group	Value	95% CI
Zoliflodacin	-7.1	± 21.9

Changes From Baseline Hematocrit Secondary · From Day -1 through Day 4

Change from baseline calculated by subtracting the Day -1 (baseline) hematocrit measurement from the Day 4 hematocrit measurement.

Group	Value	95% CI
Zoliflodacin	1.36	± 1.68

Changes From Baseline Hemoglobin Secondary · From Day -1 through Day 4

Change from baseline calculated by subtracting the Day -1 (baseline) hemoglobin measurement from the Day 4 hemoglobin measurement.

Group	Value	95% CI
Zoliflodacin	0.46	± 0.66

Changes From Baseline Red Blood Cell Count Secondary · From Day -1 through Day 4

Change from baseline calculated by subtracting the Day -1 (baseline) red blood cell count measurement from the Day 4 red blood cell count measurement.

Group	Value	95% CI
Zoliflodacin	0.150	± 0.201

Adverse events — posted to ClinicalTrials.gov

Time frame: Unsolicited Adverse Events and serious adverse events (SAEs) were collected from study product administration to Day 8.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Zoliflodacin

Serious: 0/8 (0%)

Deaths: 0/8

Other adverse events (7 terms — click to expand)

Reaction	System	Zoliflodacin
ELECTROCARDIOGRAM QT PROLONGED	Investigations	—
HEART RATE DECREASED	Investigations	—
DIARRHOEA	Gastrointestinal disorders	—
ABDOMINAL PAIN	Gastrointestinal disorders	—
NEUTROPHIL COUNT DECREASED	Investigations	—
WHITE BLOOD CELL COUNT DECREASED	Investigations	—
DERMATITIS CONTACT	Skin and subcutaneous tissue disorders	—

Data from ClinicalTrials.gov NCT03404167 adverse events section.

Sponsor's own description

The trial is to evaluate the pharmacokinetics and safety profiles of the single-dose of zoliflodacin in eight healthy male or female subjects ages 18 to 45 years inclusive. All subjects will be dosed in the morning of Day 1 in a staggered fashion with a minimum of several minutes apart. Each subject will receive a single 4g dose of zoliflodacin (2 x 2 g sachets of zoliflodacin) after at least an 8-h fast, which will continue for at least 4 h after dosing. Consumption of water will be permitted during the fasting period. Subjects will be monitored as inpatients in the Clinical Trial Unit (CTU) up to Day 4 and at the Final Visit (Day 8 ± 2). Study duration is approximately 4 weeks with subject participation duration up to 10 days (from dosing to final visit). The primary objective of this study is to evaluate the plasma PK of zoliflodacin after administration of a single 4-g oral dose under fasting conditions.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Thorough QT Study To Evaluate the Effect of Zoliflodacin, a Novel Therapeutic for Gonorrhea, on Cardiac Repolarization in Healthy Adults.
   Newman LM, Kankam M, Nakamura A, Conrad T, et al · · 2021 · cited 7× · PMID 34606332 · DOI 10.1128/aac.01292-21