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

NCT02724085 | Completed Phase 1 DMC

• 2 other identifiers: TP-271-001HHSN272201100028C
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pneumonia

Outcome Measures

Primary Outcomes (5)

• Adverse Events (AE)

  The incidence, intensity, and type of adverse events (AE) Outcome measures to be collected in support of the primary objective (safety and tolerability) include: * The incidence, intensity, and type of AEs (from time of signing of informed consent form \[ICF\] through EOS); * Changes in physical examination findings (Day -1 and EOS); * Changes in vital signs (Day -1 through EOS); * Changes in safety laboratory (chemistry, hematology, coagulation, urinalysis) results (Days -1 through EOS); and * Changes in ECG measurements (Days -1 through EOS).

  Through study completion, appromiximately 39 days

• Physical Exams

  Changes in physical examination findings

  Through study completion, appromiximately 39 days

• Vital Signs

  Changes in vital signs

  Through study completion, appromiximately 39 days

• Safety Laboratory

  Changes in safety laboratory (chemistry, hematology, coagulation, urinalysis) results

  Through study completion, appromiximately 39 days

• ECG measurements

  Changes in ECG measurements

  Through study completion, appromiximately 39 days

Secondary Outcomes (15)

• Plasma Pharmacokinetic (PK) Analysis

  Days 1-5

• Urine Pharmacokinetic (PK) Analysis

  Days 1-5

• PK parameters - Cmax

  Days 1-5

• PK parameters - Tmax

  Days 1-5

• PK parameters - C8

  Days 1-5

Study Arms (7)

Cohort A

ACTIVE COMPARATOR

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

Drug: TP-271

Cohort B

ACTIVE COMPARATOR

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

Drug: TP-271

Cohort C

ACTIVE COMPARATOR

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

Drug: TP-271

Cohort D

ACTIVE COMPARATOR

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

Drug: TP-271

Cohort E

ACTIVE COMPARATOR

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

Drug: TP-271

Cohort F

ACTIVE COMPARATOR

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

Drug: TP-271

Cohort G

ACTIVE COMPARATOR

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

Drug: TP-271

Interventions

TP-271 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 A; Cohort B; Cohort C; Cohort D; Cohort E; Cohort F; Cohort G

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Be within the age range of 18 to 50 years, inclusive, at the time of Screening.
• 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.
• Have a body mass index (BMI) ≥18.0 and ≤33.0 kg/m2.
• Be clear of any history of, and have negative screen for, HIV 1 and 2 and hepatitis B and C.
• Have the ability to communicate with the investigative site staff in a manner sufficient to carry out all protocol procedures as described.
• Females must be of non-child bearing potential, either 1-year post-menopausal or surgically sterile (bilateral oophorectomy, bilateral tubal ligation, or complete hysterectomy).
• 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.

You may not qualify if:

• 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.
• 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
• Systolic blood pressure 85 - 145 mm Hg
• Diastolic blood pressure 50 - 95 mm Hg
• Pulse rate 45 - 95 beats per minute (bpm)
• Known allergy to tetracycline antibiotics or to any of the excipients in TP-271.
• 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.

Sponsors & Collaborators

• Tetraphase Pharmaceuticals, Inc: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

PPD Phase 1 Clinic

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Pneumonia

Interventions

TP-271

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2015
• First Posted: March 31, 2016
• Study Start: December 18, 2015
• Primary Completion: September 28, 2016
• Study Completion: December 12, 2016
• Last Updated: December 13, 2021

Record last verified: 2021-12

Locations

US (1)