A Phase 1 TP-271 Oral PK Single Ascending Dose Study

NCT03024034 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: TP-271-00315-0061
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety and tolerability of up to 6 different single ascending oral doses of TP-271, ranging from 25 mg to 300 mg, in healthy adult male or female subjects.

Conditions

Bacterial Infections

Outcome Measures

Primary Outcomes (5)

• Adverse Events (AE)

  The incidence, intensity, and type of adverse events (AE) and the total number of participants experiencing AEs that are related to treatment 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, approximately 39 days

• Physical Exams

  Changes in physical examination findings

  Through study completion, approximately 39 days

• Vital Signs

  Changes in vital signs

  Through study completion, approximately 39 days

• Safety Laboratory

  Changes in safety laboratory (chemistry, hematology, coagulation, urinalysis) results that are considered abnormal, clinically significant and related to treatment

  Through study completion, approximately 39 days

• ECG measurements

  Abnormal ECG measurements that are abnormal, clinically significant and related to treatment

  Through study completion, approximately 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

Oral dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 25 mg single dose (n = 6) or matching placebo (n = 2)

Drug: TP-271

Cohort B

ACTIVE COMPARATOR

Oral dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 50 mg single dose (n = 6) or matching placebo (n = 2)

Drug: TP-271

Cohort C

ACTIVE COMPARATOR

Oral dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 100 mg single dose (n = 6) or matching placebo (n = 2)

Drug: TP-271

Cohort D

ACTIVE COMPARATOR

Oral dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 150 mg single dose (n = 6) or matching placebo (n = 2)

Drug: TP-271

Cohort E

ACTIVE COMPARATOR

Oral dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 200 mg single dose (n = 6) or matching placebo (n = 2)

Drug: TP-271

Cohort F

ACTIVE COMPARATOR

Oral dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 300 mg single dose (n = 6) or matching placebo (n = 2)

Drug: TP-271

Cohort G

ACTIVE COMPARATOR

Oral dose of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 50 mg TP 271, cross-over to 50 mg TP 271/250 mg EDTA (n = 3); 50 mg TP 271/250 mg EDTA, cross-over to 50 mg TP 271 (n = 3); matching placebo, cross over to 250 mg EDTA (n= 1); or 250 mg EDTA, cross over to matching placebo (n = 1)

Drug: TP-271

Interventions

TP-271 DRUG

single oral dose of TP 271 or placebo, randomized 3:1, doses escalating as 25 mg, 50 mg, 100 mg, 150 mg, 200 mg, and 300 mg, and a final crossover cohort of 50 mg TP-271 and 50 mg TP-271 with 250 mg of EDTA, or placebo and 250 mg of EDTA

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 Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 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
• Have a negative history of and negative screening results for human immunodeficiency virus 1 and 2 and hepatitis B and C antibodies
• Have the ability to communicate with the study unit staff in a manner sufficient to carry out all protocol procedures as described
• Female subjects 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 contraception or practice abstinence (including male subjects who had a vasectomy) from dosing through 90 days post-dosing of the study drug

You may not qualify if:

• History and/or presence of any clinically significant disease or disorder such as cardiovascular, pulmonary, renal, hepatic, neurological, gastrointestinal, endocrine, psychiatric, or mental disease or disorder, or mental or legal incapacitation, 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
• Table 3 Acceptable Out-of-Range Clinical Laboratory Values Low Chemistry Values High Chemistry Values Out-of-Range Urinalysis Values Out of Range Hematology Values Bicarbonate Chloride High or low specific gravity High hematocrit Chloride HDL cholesterol Cloudy Basophils GGT LDL cholesterol Mucus Monocytes HDL cholesterol Phosphorus Crystals MCV LDH Triglycerides Ketones MCHC LDL cholesterol Hyaline casts MCH Phosphorus High or low pH RBC Triglycerides Urobilinogen a Bicarbonate \>18 mEq/L. b Ketonuria is acceptable only when the concurrent blood glucose is normal. c Measured when monitoring the serum bilirubin concentration. Abbreviations: GGT = gamma-glutamyltransferase; HDL = high-density lipoprotein; LDH = lactate dehydrogenase; LDL = low-density lipoprotein; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular volume; RBC = red blood cell.
• Known allergy to tetracycline antibiotics, EDTA, or any of the excipients in TP 271
• Clinically significant abnormality on a 12-lead ECG including the following:
• Rhythm other than sinus
• Corrected QT interval using Fridericia's formula (QTcF) \>450 msec
• Evidence of second- or third-degree atrioventricular (AV) block
• Pathological Q-waves (defined as a Q-wave \>40 msec or depth \>0.4 to 0.5 mV)
• Evidence of ventricular pre-excitation
• Evidence of complete left bundle branch block (BBB), right BBB, or incomplete left BBB
• Intraventricular conduction delay with QRS duration \>120 msec
• ST segment abnormalities unless judged by the Investigator to be non pathologic
• History of seizures
• A history within 3 years of positive result on urine screen for drugs of abuse or a positive result at Screening for any of the following drugs of abuse: tetrahydrocannabinols, cocaine, opioids, phencyclidines, amphetamine, benzodiazepine, and barbiturates
• Use of tobacco, nicotine, or nicotine-replacement products within 3 months prior to administration of study drug through the last study visit

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

Bacterial Infections

Interventions

TP-271

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Study Design

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

Study Record Dates

• First Submitted: January 9, 2017
• First Posted: January 18, 2017
• Study Start: March 2, 2017
• Primary Completion: December 1, 2017
• Study Completion: June 4, 2018
• Last Updated: December 13, 2021

Record last verified: 2021-12

Locations

US (1)