A Phase 1 Study to Assess the Safety, Tolerability and PK of IV TP-271

NCT ID: NCT02724085

Last Updated: 2021-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

57 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-18

Study Completion Date

2016-12-12

Brief Summary

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This is a single-center, randomized, placebo-controlled, double-blind, single-ascending-dose, inpatient study to assess the safety, tolerability, and pharmacokinetics of TP-271 in healthy subjects. Subjects aged 18 to 50 years who fulfill the inclusion/exclusion criteria will be enrolled in this study.

Detailed Description

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Up to seven cohorts of eight subjects each (up to a total of 56 subjects) will be enrolled. The eight subjects within each cohort will be randomized 6:2 to receive a single intravenous dose of TP-271 or placebo. The planned doses are:

Cohort A: 0.15 mg/kg Cohort B: 0.45 mg/kg Cohort C: 1.0 mg/kg Cohort D: 2.0 mg/kg Cohort E: 3.0 mg/kg Cohort F: 4.0 mg/kg Cohort G: 5.0 mg/kg

Doses of IMP will be administered intravenously on the morning of Day 1 following an overnight fast (minimum 8 hours).

During the Screening Period (within the 28 days prior to the subject receiving TP-271 or placebo) each subject will be assessed for eligibility. Each subject must sign and date an ICF prior to undergoing any study-related procedures.

All cohorts will follow the same study design (Figure 1). On Day -1, subjects will be admitted to the study unit so their eligibility can be confirmed. Subjects will be required to stay overnight at the study unit on Day -1. On Day 1, eligible subjects will be enrolled and randomized to receive either TP-271 or placebo. Subjects will be required to stay at the study unit from Day 1 through Day 5 to assess safety and obtain required PK samples. On Day 5, subjects will be discharged from the study unit. A final safety assessment will be performed once between Day 7 and Day 10 following the subject's dose of IMP.

Conditions

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Pneumonia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Cohort A

IV dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 0.15 mg/kg single dose, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion

Group Type ACTIVE_COMPARATOR

TP-271

Intervention Type DRUG

TP-271 is a novel, broad-spectrum tetracycline with potent activity against multidrug-resistant pathogens. It will be administered intravenously (IV) in doses ranging from 0.15 to 5.0 mg/kg

Cohort B

IV dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 0.45 mg/kg single dose, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion

Group Type ACTIVE_COMPARATOR

TP-271

Intervention Type DRUG

TP-271 is a novel, broad-spectrum tetracycline with potent activity against multidrug-resistant pathogens. It will be administered intravenously (IV) in doses ranging from 0.15 to 5.0 mg/kg

Cohort C

IV dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 1.0 mg/kg single dose, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion

Group Type ACTIVE_COMPARATOR

TP-271

Intervention Type DRUG

TP-271 is a novel, broad-spectrum tetracycline with potent activity against multidrug-resistant pathogens. It will be administered intravenously (IV) in doses ranging from 0.15 to 5.0 mg/kg

Cohort D

IV dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 2.0 mg/kg single dose, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion

Group Type ACTIVE_COMPARATOR

TP-271

Intervention Type DRUG

TP-271 is a novel, broad-spectrum tetracycline with potent activity against multidrug-resistant pathogens. It will be administered intravenously (IV) in doses ranging from 0.15 to 5.0 mg/kg

Cohort E

IV dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 3.0 mg/kg single dose, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion

Group Type ACTIVE_COMPARATOR

TP-271

Intervention Type DRUG

TP-271 is a novel, broad-spectrum tetracycline with potent activity against multidrug-resistant pathogens. It will be administered intravenously (IV) in doses ranging from 0.15 to 5.0 mg/kg

Cohort F

IV dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 4.0 mg/kg single dose, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion

Group Type ACTIVE_COMPARATOR

TP-271

Intervention Type DRUG

TP-271 is a novel, broad-spectrum tetracycline with potent activity against multidrug-resistant pathogens. It will be administered intravenously (IV) in doses ranging from 0.15 to 5.0 mg/kg

Cohort G

IV dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 5.0 mg/kg single dose, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion

Group Type ACTIVE_COMPARATOR

TP-271

Intervention Type DRUG

TP-271 is a novel, broad-spectrum tetracycline with potent activity against multidrug-resistant pathogens. It will be administered intravenously (IV) in doses ranging from 0.15 to 5.0 mg/kg

Interventions

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TP-271

TP-271 is a novel, broad-spectrum tetracycline with potent activity against multidrug-resistant pathogens. It will be administered intravenously (IV) in doses ranging from 0.15 to 5.0 mg/kg

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Be within the age range of 18 to 50 years, inclusive, at the time of Screening.
2. Voluntarily sign an IRB/Research Ethics Committee (IRB/REC)-approved ICF to participate in the study after all relevant aspects of the study have been explained and discussed with the subject and before undergoing any study related procedures.
3. Have a body mass index (BMI) ≥18.0 and ≤33.0 kg/m2.
4. Be clear of any history of, and have negative screen for, HIV 1 and 2 and hepatitis B and C.
5. Have the ability to communicate with the investigative site staff in a manner sufficient to carry out all protocol procedures as described.
6. Females must be of non-child bearing potential, either 1-year post-menopausal or surgically sterile (bilateral oophorectomy, bilateral tubal ligation, or complete hysterectomy).
7. Male subjects must be willing and able to use a barrier method of birth control or practice abstinence (even if they have had a vasectomy) from dosing through 90 days after the dose of IMP.

Exclusion Criteria

1. History and/or presence of any clinically significant disease or disorder such as cardiovascular, pulmonary, renal, hepatic, neurological, gastrointestinal, and psychiatric/mental disease/disorders, which, in the opinion of the PI, may either put the subject at risk because of participation in the study, influence the results of the study, or influence the subject's ability to participate in the study.
2. Clinical laboratory values that fall outside the eligibility range specified in the table in Appendix C are exclusionary. For the laboratory values that are not included in Appendix C, values outside of the reference range are exclusionary with the following exceptions:

Low Chemistry Values High Chemistry Values Out of Range UA Out of Range Hematology Bicarbonate (\> 18 mEq/L Chloride GGT HDL Cholesterol LDH LDL Cholesterol Phosphorus Triglycerides Chloride HDL Cholesterol LDL Cholesterol Phosphorus Triglycerides High or low specific gravity Cloudy Mucus Crystals Ketones (when blood glucose is normal) Hyaline casts High or low pH

High hematocrit Basophils Monocytes MCV MCHC MCH RBC
3. Blood pressure and pulse outside of the following ranges are exclusionary:

* Systolic blood pressure 85 - 145 mm Hg
* Diastolic blood pressure 50 - 95 mm Hg
* Pulse rate 45 - 95 beats per minute (bpm)
4. Known allergy to tetracycline antibiotics or to any of the excipients in TP-271.
5. Clinically significant abnormal 12-lead ECG, including the following:

* Rhythm other than sinus, QTc interval using Fridericia's formula (QTcF) \>450 msec;
* Evidence of second- or third-degree atrioventricular (AV) block;
* Pathological Q-waves (defined as Q-wave \>40 msec or depth \>0.4 to 0.5 mV);
* Evidence of ventricular pre-excitation;
* Electrocardiographic evidence of complete left bundle branch block, right bundle branch block (RBBB), incomplete LBBB;
* Intraventricular conduction delay with QRS duration \>120 msec;
* ST segment abnormalities unless judged by the Investigator to be non-pathologic.
6. History of seizures.
7. A history within 3 years of Screening of drug abuse (including benzodiazepines, opioids, amphetamine, and cocaine) or a positive drug result at Screening for any of these drugs of abuse. Also excluded are subjects who test positive for cannabinoids (THCs).
8. Use of tobacco, nicotine, or nicotine-replacement products within the 3 months prior to the dose of study drug through the last study visit.
9. Typical weekly alcohol consumption of 7 or more alcoholic drinks. One drink is defined as 1 glass of beer (approximately 10 to 12 oz) or 1 can (12 oz) of beer, 1 glass of wine (approximately 4 to 5 oz), or 1 glass of distilled spirits (hard liquor) containing 1 oz of the liquor (1 oz of liquid is approximately 30 mL).
10. Alcohol consumption within 48 hours prior to dosing.
11. Participation in a clinical trial within 10 half-lives of the prior study treatment or the past 3 months if the half-life is unknown of dose or planned participation in another trial in addition to this one during the trial.
12. History of difficulty in donating blood or poor venous access.
13. Subject has donated blood (1 unit or 350 mL) within 1 month prior to receiving test material or plans to donate prior to receiving test material or during the trial.
14. Use of any prescription or non-prescription medication, including vitamins or herbal medications, within 7 days, or 5 half-lives (if known), whichever is longer, prior to dosing. The use of acetaminophen, naproxen, and ibuprofen is permitted except for within 24 hours prior to dosing. (Note: Subjects must refrain from taking herbal or dietary supplements or prescription drug therapy for the duration of the study.)
15. Unwillingness or inability to follow the procedures outlined in the protocol. Subject is mentally or legally incapacitated
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Tetraphase Pharmaceuticals, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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PPD Phase 1 Clinic

Austin, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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HHSN272201100028C

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

TP-271-001

Identifier Type: -

Identifier Source: org_study_id