A Single-Dose, Randomized, Placebo- and Active-Control, Four-Way, Cross-Over Study for the Evaluation of the Effect of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) on the QT/QTc Intervals in Adult Healthy Subjects

NCT04238195 | Completed Phase 1 FDA Drug

• 1 other identifier: SPR994-104
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind (with respect to Tebipenem pivoxil hydrobromide \[TBPM-PI-HBr\]/placebo only), placebo- and active-control, single-dose, 4-way crossover study that will enroll 24 healthy adult male and female subjects. There will be a washout period of at least 7 days between dosing in each period and each subject will receive all 4 treatments over 4 periods in a crossover study design.

Conditions

TQT Study

Keywords

TQT

Outcome Measures

Primary Outcomes (1)

• To evaluate the effect of a single therapeutic and supratherapeutic dose of TBPM-PI-HBr on the heart rate corrected QT interval (QTc) by assessing concentration-QT (C-QT) relationship using exposure-response modeling.

  Holter monitors will be used to collect continuous 12-lead electrocardiogram (ECG) data on Day 1. Triplicate 10-second, 12-lead ECG recordings will be extracted from the Holter monitor data within a 5-minute time window prior to the pharmacokinetic (PK) blood samples collected as close to the exact time point as possible

  Pre-dose through 24 hours post-dose

Secondary Outcomes (14)

• 1. To evaluate the effect of a single therapeutic and supratherapeutic dose of TBPM-PI-HBr on other electrocardiogram (ECG) parameters.

  Pre-dose through 24 hours post-dose

• 1. To evaluate the effect of a single therapeutic and supratherapeutic dose of TBPM-PI-HBr on other electrocardiogram (ECG) parameters.

  Pre-dose through 24 hours post-dose

• 1. To evaluate the effect of a single therapeutic and supratherapeutic dose of TBPM-PI-HBr on other electrocardiogram (ECG) parameters.

  Pre-dose through 24 hours post-dose

• 1. To evaluate the effect of a single therapeutic and supratherapeutic dose of TBPM-PI-HBr on other electrocardiogram (ECG) parameters.

  Pre-dose through 24 hours post-dose

• 1. To evaluate the effect of a single therapeutic and supratherapeutic dose of TBPM-PI-HBr on other electrocardiogram (ECG) parameters.

  Pre-dose through 24 hours post-dose

Study Arms (4)

Treatment A

EXPERIMENTAL

600 mg TBPM-PI-HBr (2 x 300 mg tablets) and TBPM-PI-HBr-matching placebo (2 x matching placebo tablets) administered at Hour 0 on Day 1.

Drug: Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) + Placebo; Other: Placebo for Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr)

Treatment B

EXPERIMENTAL

1200 mg TBPM-PI-HBr (4 x 300 mg tablets) administered at Hour 0 on Day 1.

Drug: Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr)

Treatment C

PLACEBO COMPARATOR

TBPM-PI-HBr-matching placebo (4 x matching placebo tablets) administered at Hour 0 on Day 1.

Other: Placebo for Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr)

Treatment D

OTHER

Positive Control - unblinded: 400 mg moxifloxacin (1 x 400 mg tablet) administered at Hour 0 on Day 1.

Drug: Moxifloxacin 400mg

Interventions

Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) + Placebo DRUG

Treatment A: Subjects receive TBPM-PI-HBr + matching Placebo.

Also known as: SPR994

Treatment A

Moxifloxacin 400mg DRUG

Treatment D: Subjects receive 1 400 mg tablet of moxifloxacin administered in an open label manner.

Also known as: Avelox

Treatment D

Placebo for Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) OTHER

Treatment C: Subjects receive TBPM-PI-HBr matching placebo.

Treatment A; Treatment C

Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) DRUG

Treatment B: Subjects receive TBPM-PI-HBr.

Also known as: SPR994

Treatment B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy, adult, male or female, 18-65 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 dosing and throughout the study, based on subject self- reporting.
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at screening.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.
• No clinically significant history or presence of ECG findings as judged by the PI or qualified designee at screening and prior to dosing of Period 1, including each criterion as listed below:
• Normal sinus rhythm (heart rate between 50 and 100 bpm, inclusive);
• QTcF interval (Fridericia's correction to the QT interval) ≤ 450 msec;
• QRS interval \< 110 msec;
• PR interval \< 220 msec.
• For a female of childbearing potential: either be sexually inactive (abstinent as a lifestyle) for 3 months prior to the first dosing and throughout the study or be using one of the following acceptable birth control methods:
• non-hormone releasing intrauterine device for at least 3 months prior to the first dosing and throughout the study.
• surgical sterilization of the partner (vasectomy for 4 months minimum prior to the first dosing. In addition, female subjects of childbearing potential will be advised to remain sexually inactive or to keep the same birth control method for at least 28 days following the last dose.
• For a female of non-childbearing potential: must have undergone one of the following sterilization procedures at least 6 months prior to the first dosing:
• hysteroscopic sterilization (with confirmation of procedure success with hystosalpingogram);
• bilateral tubal ligation or bilateral salpingectomy;

You may not qualify if:

• Subjects must not be enrolled in the study if they meet any of the following criteria:
• 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 or designee.
• History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
• History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s) or related compounds (especially fluoroquinolone-, carbapenem-, penicillin-, and cephalosporin-antibiotics sensitivity).
• History or presence of any of the following, deemed clinically significant by the PI or designee:
• Ventricular pre-excitation syndrome (Wolff-Parkinson White syndrome);
• Arrhythmia or history of arrhythmia requiring medical intervention;
• Risk factors for Torsade de Pointes (e.g., heart failure, cardiomyopathy, or family history of Long QT Syndrome);
• Sick sinus syndrome, second or third degree atrioventricular block, myocardial infarction, pulmonary congestion, symptomatic or significant cardiac arrhythmia, prolonged QTcF interval, or conduction abnormalities.
• Allergy to ECG electrode adhesive patches, band aids, adhesive dressing or medical tape.
• History of epilepsy or seizure disorder.
• History of known genetic metabolism anomaly associated with carnitine deficiency (e.g., carnitine transporter defect, methylmalonic aciduria, propionic acidemia).
• Female subjects with a positive pregnancy test or who are lactating.

Sponsors & Collaborators

• Spero Therapeutics: lead
• Celerion: collaborator

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

tebipenem; 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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A computerized randomization scheme will be created by a CRO-statistician and it shall be considered blinded (as per the following). The randomization is available only to the pharmacy staff that is preparing the drug who will not be involved in any other aspect of the study including administration of the drug. The randomization will also be available to the bioanalytical laboratory as sample analyses will be treatment-dependent. It will not be made available to the Sponsor, subjects, or members of the staff responsible for the monitoring and evaluation of safety assessments. On Day 1 of each period, subjects will receive a single oral therapeutic dose of TBPM-PI-HBr (Treatment A), supratherapeutic dose of TBPM-PI-HBr (Treatment B), placebo (Treatment C), or moxifloxacin (Treatment D) according to the randomization scheme.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Over 4 separate treatment periods, each separated by a 7-day washout period, all subjects will receive a single dose of 4 different study treatments.The design is constructed from three 4x4 Latin Squares balanced for carry-over effects.

Study Record Dates

• First Submitted: January 16, 2020
• First Posted: January 23, 2020
• Study Start: January 19, 2020
• Primary Completion: February 26, 2020
• Study Completion: February 26, 2020
• Last Updated: March 13, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)