Clinical trial NCT02505997: Study to Evaluate the Effect of Delafloxacin on the Pharmacokinetics of Midazolam in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: VA Drug Interactions
Lead sponsor: Melinta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-07-22
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Midazolam and 1-hydroxymidazolam Plasma PK: AUC0-t
timeFrame: Days 1 and 8
measure: Midazolam and 1-hydroxymidazolam Plasma PK: AUC0-inf
timeFrame: Days 1 and 8
measure: Midazolam and 1-hydroxymidazolam Plasma PK: Cmax
timeFrame: Days 1 and 8
Secondary outcomes:
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD Development, LP
state: Texas
Study officials:
affiliation: Melinta Therapeutics, Inc.
name: Sue Cammarata, MD
role: STUDY_DIRECTOR
References:
citation: 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.