Study to Evaluate the Effect of Delafloxacin on the Pharmacokinetics of Midazolam in Healthy Subjects

A Phase I Study to Evaluate the Effect of Repeated Oral Doses of Delafloxacin on the Pharmacokinetics of a Single Oral Dose of Midazolam in Healthy Subjects

The purpose of this study is to evaluate the effect of repeated doses of oral delafloxacin on the pharmacokinetic (PK) profile of a single oral dose of midazolam.

Study Overview

• Status: Completed
• Conditions: VA Drug Interactions
• Intervention / Treatment: Drug: Midazolam; Drug: Delafloxacin

Detailed Description

This study will evaluate the effect of repeated doses of oral delafloxacin on the PK profile of a single oral dose of midazolam. The study will also evaluate the pharmacokinetics, safety, and tolerability of repeated oral doses of delafloxacin in healthy male and female subjects and to obtain a steady state PK profile for oral delafloxacin.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Development, LP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• No clinically important abnormal physical findings.
• No clinically significant laboratory abnormalities.
• Normal (or abnormal but not clinically significant) ECG measurements.
• Body mass index between 18.0 and 32.0 kg/m2.
• Normal (or abnormal but not clinically significant) blood pressure and pulse rate measurements. methylxanthine-containing beverages or food
• Non-smoker

Exclusion Criteria:

• Received any investigational drug within 8 weeks before administration of the first dose of the study drug
• Female who is pregnant, has a positive pregnancy test, or is breastfeeding.
• Positive test result for amphetamines, barbiturates, benzodiazepines, cocaine metabolites, opiates, cannabinoids, methylenedioxymethamphetamine, cotinine, or alcohol in urine at Screening or Day -1.
• Positive screening test for hepatitis B surface antigen, hepatitis C, and/or human immunodeficiency virus antibodies.
• Any surgical or medical condition that, in the judgment of the investigator, might interfere with the absorption, distribution, metabolism, or excretion of the drug.
• Used any medication (prescription or over-the-counter, including health supplements and herbal remedies, with the exception of acetaminophen, as defined in exclusion number 8) within 2 weeks (4 weeks for drugs or substances known to inhibit or induce CYP enzymes and/or P-gp including St. John's wort [Hypericum perforatum]) or 5 half-lives (whichever is longer) before the first dose of study drug.
• Used an oral or IV antibiotic within 4 weeks of administration of the first dose of the study drug.
• Routinely or chronically used more than 2 g of acetaminophen daily.
• Performed strenuous activity, sunbathing, and/or contact sports within 96 hours (4 days) before entry into the clinical study site on Day -1, and for the duration of the study.
• Donated or lost greater than 400 mL of blood in the 30 days before administration of the first dose of the study drug.
• History of clinically significant GI disease, or gastroenteritis (vomiting or diarrhea) or any history of GI bleeding (excluding bleeding from hemorrhoids)
• History of any significant drug allergy
• History of any drug or alcohol abuse in the past 2 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Midazolam/Delafloxacin; Each subject will receive a single 5 mg oral dose of midazolam syrup on Day 1, oral 450 mg delafloxacin tablets twice daily (Q12h) for Days 3 to 8, and co-administered a single 5 mg oral dose of midazolam syrup in the AM on Day 8.	Drug: Midazolam; Single 5 mg oral dose of midazolam syrup given in the AM on Day 1 and Day 8.; Drug: Delafloxacin; Oral 450 mg delafloxacin tablets given twice daily (Q12h) on Days 3 to 8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Midazolam and 1-hydroxymidazolam Plasma PK: AUC0-t	Days 1 and 8
Midazolam and 1-hydroxymidazolam Plasma PK: AUC0-inf	Days 1 and 8
Midazolam and 1-hydroxymidazolam Plasma PK: Cmax	Days 1 and 8

Collaborators and Investigators

• Sponsor: Melinta Therapeutics, Inc.

Publications and helpful links

General Publications

• Paulson SK, Wood-Horrall RN, Hoover R, Quintas M, Lawrence LE, Cammarata SK. The Pharmacokinetics of the CYP3A Substrate Midazolam After Steady-state Dosing of Delafloxacin. Clin Ther. 2017 Jun;39(6):1182-1190. doi: 10.1016/j.clinthera.2017.04.009. Epub 2017 May 9.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: June 23, 2015
• First Submitted That Met QC Criteria: July 21, 2015
• First Posted (Estimate): July 22, 2015

Study Record Updates

• Last Update Posted (Estimate): December 16, 2016
• Last Update Submitted That Met QC Criteria: December 15, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: ML-3341-118