Study Evaluating the Effect of ETX2514 on Cardiac Repolarization in Healthy Male or Female Volunteers

NCT03985410 | Completed Phase 1 FDA Drug

• 1 other identifier: CS2514-2018-0003
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to evaluate the effects of supratherapeutic ETX2514 plasma concentrations on the heart rate-corrected QT interval (QTc).

Conditions

Acinetobacter Baumannii-calcoaceticus Complex Infections

Keywords

Acinetobacter baumannii-calcoaceticus; complex infections; ETX2514; cardiac repolarization; heart rate-corrected QT interval (QTc)

Outcome Measures

Primary Outcomes (1)

• Placebo-corrected change from Baseline in Fridericia-corrected QTc (QTcF) (ΔΔQTcF)

  Baseline; up to Day 22

Secondary Outcomes (9)

• Change from baseline in heart rate (HR) (ΔHR)

  Baseline; up to Day 22

• Change from Baseline in QTcF (ΔQTcF)

  Baseline; up to Day 22

• Change from Baseline in the PR interval (ΔPR)

  Baseline; up to Day 22

• Change from Baseline in the QRS interval (ΔQRS)

  Baseline; up to Day 22

• Placebo-corrected change from Baseline in HR (ΔΔHR)

  Baseline; up to Day 22

Study Arms (6)

Treatment Sequence ABC

EXPERIMENTAL

Participants will receive a single 3-hour intravenous (IV) infusion of 4 grams (g) of ETX2514 (supratherapeutic dose) (Treatment A), followed by a single 3-hour IV infusion of placebo for ETX2514 (Treatment B), followed by a single 3-hour IV infusion of placebo for ETX2514 and a single oral dose of 400 milligrams (mg) open-label moxifloxacin given at the end of the infusion (Treatment C). There will be 7 ± 2 days washout between treatments.

Drug: ETX2514; Drug: Placebo; Drug: moxifloxacin

Treatment Sequence ACB

EXPERIMENTAL

Participants will receive a single 3-hour IV infusion of 4 g of ETX2514 (supratherapeutic dose) (Treatment A), followed by a single 3-hour IV infusion of placebo for ETX2514 and a single oral dose of 400 mg open-label moxifloxacin given at the end of the infusion (Treatment C), followed by a single 3-hour IV infusion of placebo for ETX2514 (Treatment B). There will be 7 ± 2 days washout between treatments.

Drug: ETX2514; Drug: Placebo; Drug: moxifloxacin

Treatment Sequence BAC

EXPERIMENTAL

Participants will receive a single 3-hour IV infusion of placebo for ETX2514 (Treatment B), followed by a single 3-hour IV infusion of 4 g of ETX2514 (supratherapeutic dose) (Treatment A), followed by a single 3-hour IV infusion of placebo for ETX2514 and a single oral dose of 400 mg open-label moxifloxacin given at the end of the infusion (Treatment C). There will be 7 ± 2 days washout between treatments.

Drug: ETX2514; Drug: Placebo; Drug: moxifloxacin

Treatment Sequence BCA

EXPERIMENTAL

Participants will receive a single 3-hour IV infusion of placebo for ETX2514 (Treatment B), followed by a single 3-hour IV infusion of placebo for ETX2514 and a single oral dose of 400 mg open-label moxifloxacin given at the end of the infusion (Treatment C), followed by a single 3-hour IV infusion of 4 g of ETX2514 (supratherapeutic dose) (Treatment A). There will be 7 ± 2 days washout between treatments.

Drug: ETX2514; Drug: Placebo; Drug: moxifloxacin

Treatment Sequence CAB

EXPERIMENTAL

Participants will receive a single 3-hour IV infusion of placebo for ETX2514 and a single oral dose of 400 mg open-label moxifloxacin given at the end of the infusion (Treatment C), followed by a single 3-hour IV infusion of 4 g of ETX2514 (supratherapeutic dose) (Treatment A), followed by a single 3-hour IV infusion of placebo for ETX2514 (Treatment B). There will be 7 ± 2 days washout between treatments.

Drug: ETX2514; Drug: Placebo; Drug: moxifloxacin

Treatment Sequence CBA

EXPERIMENTAL

Participants will receive a single 3-hour IV infusion of placebo for ETX2514 and a single oral dose of 400 mg open-label moxifloxacin given at the end of the infusion (Treatment C), followed by a single 3-hour IV infusion of placebo for ETX2514 (Treatment B), followed by a single 3-hour IV infusion of 4 g of ETX2514 (supratherapeutic dose) (Treatment A). There will be 7 ± 2 days washout between treatments.

Drug: ETX2514; Drug: Placebo; Drug: moxifloxacin

Interventions

ETX2514 DRUG

intravenous infusion

Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

Placebo DRUG

intravenous infusion

Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

moxifloxacin DRUG

oral tablet

Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, adult, male or female, 18-55 years of age, inclusive, at Screening
• Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dose
• Must weigh at least 60 kilograms (kg) for males or 52 kg for females and have a body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/meters squared (m\^2) at Screening.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the Principal Investigator (PI)
• Women of childbearing potential (i.e., not post-menopausal or surgically sterilized) must have a negative serum pregnancy test before randomization. Participating heterosexual women of childbearing potential must be willing to consistently use 2 highly effective methods of contraception (i.e., condom with spermicide, combined oral contraceptive, implant, injectable, indwelling intrauterine device, or a vasectomized partner) from Screening until at least 30 days after administration of the last dose of study drug; and
• Non-childbearing women must have had a hysterectomy, surgical sterilization, or be postmenopausal at least 12 months prior to Screening.
• Male participants must be willing to use condoms with spermicide during sexual intercourse from Screening until at least 90 days after administration of the last dose of study drug.
• Male participants with a vasectomy must have had the vasectomy at least 90 days prior to randomization.
• Male participants must agree not to donate sperm from the Screening period through 90 days after the last dose.
• Understands the study procedures in the informed consent form and is willing and able to comply with the protocol
• Able to swallow tablets
• Supine blood pressure between 90/40 millimeters of mercury (mmHg) and 140/90 mmHg (inclusive) at Screening
• No clinically significant history or presence of ECG findings as judged by the PI at Screening and check-in, including each criterion as listed below:
• Normal sinus rhythm (heart rate between 45 beats per minute \[bpm\] and 100 bpm inclusive);
• Fridericia-corrected QTc (QTcF) interval \< 450 milliseconds (msec);

You may not qualify if:

• Participant is mentally or legally incapacitated or has significant emotional problems at the time of the Screening visit or expected during the conduct of the study.
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI
• History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the participant by their participation in the study
• History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose of study drug
• History or presence of hypersensitivity or idiosyncratic reaction to the study drugs, related compounds, or inactive ingredients
• History of significant multiple and/or severe allergies (e.g., latex allergy, band aids, adhesive dressing, or medical tape), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs
• Female participants who are pregnant or lactating
• Positive urine drug or alcohol results at Screening or check-in
• Positive results at Screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV)
• Unable to refrain from or anticipates the use of:
• Any drug, including prescription and non-prescription medications (including antacids), herbal remedies, or vitamin supplements (especially those containing magnesium, aluminum, iron, or zinc) beginning 14 days prior to the first dose of study drug and throughout the study. Co-administration of ETX2514 and probenecid is prohibited.
• Any drugs known to be significant inhibitors or inducers of cytochrome P450 (CYP) enzymes and/or permeability glycoprotein (P-gp), including St. John's Wort, for 28 days prior to the first dose of study drug and throughout the study.
• Has been on a diet incompatible with the on-study diet (including an extreme diet which resulted in a significant weight change for whatever reason), in the opinion of the PI, within the 28 days prior to the first dose of study drug, and throughout the study
• Donation of blood or significant blood loss more than 500 milliliters (mL) within 56 days prior to the first dose of study drug
• Plasma donation within 7 days prior to the first dose of study drug

Sponsors & Collaborators

• Entasis Therapeutics: lead

Study Sites (1)

Pharmaron Clinical Pharmacology Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Interventions

durlobactam; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The administration of ETX2514 and ETX2514 placebo will be double-blinded. Placebo and moxifloxacin (Treatment Period C) will be administered open-label.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2019
• First Posted: June 13, 2019
• Study Start: May 23, 2019
• Primary Completion: July 24, 2019
• Study Completion: July 24, 2019
• Last Updated: August 30, 2019

Record last verified: 2019-08

Locations

US (1)