A Phase 1 Safety and PK Study of IV TP-271

NCT03234738 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: TP-271-002HHSN272201100028C
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, randomized, placebo-controlled, double-blind, multiple-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

Bacterial Infections

Outcome Measures

Primary Outcomes (5)

• Adverse Events

  Incidence, intensity, and type of adverse events (AEs) from the time of signing the informed consent form (ICF) through the EOS Visit

  Throughout the study, ~ 49 days

• Physical Exams

  Changes in physical examination findings between Day -1 and the EOS Visit

  ~ 20 days

• Vital Signs

  Changes in vital signs from Day -1 through the EOS Visit

  ~ 20 days

• Safety Laboratory Results

  Changes in safety laboratory (clinical chemistry, electrolytes, hematology, blood glucose, and coagulation) results from Day -1 through the EOS Visit

  ~ 20 days

• ECG measurements

  Changes in electrocardiogram (ECG) measurements from Day -1 through the EOS Visit

  ~ 20 days

Secondary Outcomes (2)

• Assess the Pharmacokinetics (PK) of TP-271in Plasma

  ~11 days

• Assess the Pharmacokinetics (PK) of TP-271 in Urine

  ~11 days

Study Arms (5)

Cohort A

ACTIVE COMPARATOR

Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 0.5 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion

Drug: TP-271; Drug: Placebo

Cohort B

ACTIVE COMPARATOR

Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 1.0 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion

Drug: TP-271; Drug: Placebo

Cohort C

ACTIVE COMPARATOR

Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 2.0 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion

Drug: TP-271; Drug: Placebo

Cohort D

ACTIVE COMPARATOR

Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 2.5 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion

Drug: TP-271; Drug: Placebo

Cohort E

ACTIVE COMPARATOR

Multiple IV doses of TP-271, a novel, broad-spectrum tetracycline-class antibiotic, 3.0 mg/kg once daily for 7 days, 60 minute infusion or Placebo - sterile 0.45% saline for 60 minute IV infusion

Drug: TP-271; Drug: Placebo

Interventions

TP-271 DRUG

multiple oral doses of TP-271 or placebo, dosed once daily for 7 days, randomized 3:1, doses escalating as 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 2.5 mg/kg, and 3.0 mg/kg

Cohort A; Cohort B; Cohort C; Cohort D; Cohort E

Placebo DRUG

Placebo is sterile 0.45% saline randomized 3:1 to receive

Cohort A; Cohort B; Cohort C; Cohort D; Cohort E

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
• For female subjects, be of non-childbearing potential, either 1 year postmenopausal or surgically sterile (bilateral oophorectomy, bilateral tubal ligation, or complete hysterectomy)
• For male subjects, be willing and able to use a barrier method of contraception or practice abstinence (including males who had a vasectomy) from dosing through 90 days after administration of the final dose of 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 or Sub-Investigator(s), 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
• Known allergy to tetracycline antibiotics or to 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 block
• Pathological Q-waves (defined as 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 PI or Sub-Investigator(s) to be non pathologic
• History of seizures
• History within 3 years of a positive result on a 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 the study drug through the last visit
• Typical weekly alcohol consumption of 7 or more alcoholic drinks, where 1 alcoholic drink is defined as 1 glass of beer (approximately 10 to 12 oz), 1 can (12 oz) of beer, 1 glass of wine (approximately 4 to 5 oz), or distilled spirits (approximately 1 oz or 30 mL of liquor)

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
• Masking Details: IV bags and lines are covered to prevent unblinding.
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Five Multiple-Ascending Doses

Study Record Dates

• First Submitted: July 6, 2017
• First Posted: July 31, 2017
• Study Start: August 16, 2017
• Primary Completion: January 2, 2018
• Study Completion: January 2, 2018
• Last Updated: December 13, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)