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

NCT03450187 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: TP-271-004
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, single-center, randomized, placebo-controlled, double-blind, multiple ascending-dose study to assess the safety, tolerability, and PK of oral TP-271 in healthy adult subjects. Male or female 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 (15)

• Adverse Events

  Incidence, intensity, and type of adverse events.

  From the time of signing of the informed consent form throughout study completion (approximately 39 days)

• A Directed Physical Examination including chest/respiratory

  changes in physical examination findings for chest/respiratory

  Day -1 to the End of Study visit, Day 21

• A Directed Physical Examination including heart/cardiovascular

  Changes in Physical Examination including heart/cardiovascular

  Day -1 to the End of study visit, Day 21

• Vital Signs including Pulse Rate

  Changes in Pulse Rate

  Day -1 to the End of study visit, Day 21

• Vital Signs including respiration rate

  Changes in respiration rate

  Day -1 to the End of study visit, Day 21

• Vital Signs including body temperature

  Changes in body temperature

  Day -1 to the end of study visit, Day 21

• Vital Signs including blood pressure

  Changes in blood pressure

  Day -1 to the End of study visit, Day 21

• ECG measurements including PR interval

  Changes in PR interval \> or=20

  Day -1 to the End of study visit, Day 21

• ECG measurements including QRS interval

  Changes in QRS interval\> or=10

  Day -1 to the end of study visit, Day 21

• ECG measurements including QTcF interval

  Changes in QTcF interval 30 to 60, \> or =60

  Day -1 to the end of study visit, Day 21

• Safety Laboratory results including clinical chemistry

  Changes in safety laboratory results including clinical chemistry

  Day -1 to the End of study visit, Day 21

• Safety Laboratory results including electrolytes

  Changes in safety laboratory results including electrolytes

  Day -1 to the End of study visit, Day 21

• Safety Laboratory results including hematology

  Changes in safety laboratory results including hematology

  Day -1 to the End of study visit, Day 21

• Safety Laboratory results including blood glucose

  Changes in Safety laboratory results including glucose

  Day -1 to the End of study visit, Day 21

• Safety Laboratory results including coagulation

  Changes in Safety Laboratory results including coagulation

  Day -1 to the End of study visit, Day 21

Secondary Outcomes (12)

• Plasma concentrations

  Days 1-7

• Urine pharmacokinetics

  Days 1-7

• PK parameters - Cmax

  Days 1-7

• PK parameters- Tmax

  Days 1-7

• PK parameters AUC (0-last)

  Days 1-7

Study Arms (5)

Cohort A

ACTIVE COMPARATOR

50 mg TP-271 q24 (n=6), a novel, broad-spectrum tetracycline-class antibiotic or matching placebo (n=2) once daily for 7 days.

Drug: TP-271

Cohort B

ACTIVE COMPARATOR

100 mg TLP-271 q24 (n=6), a novel, broad spectrum tetracycline-class antibiotic or matching placebo (n=2) once daily for 7 days.

Drug: TP-271

Cohort C

ACTIVE COMPARATOR

200 mg TP-271 q24 (n=6), a novel, broad spectrum tetracycline-class antibiotic or matching placebo (n=2) once daily for 7 days.

Drug: TP-271

Cohort D

ACTIVE COMPARATOR

300 mg TP-271 q24 (n=6), a novel, broad spectrum tetracycline-class antibiotic or matching placebo (n=2) once daily for 7 days.

Drug: TP-271

Cohort E

ACTIVE COMPARATOR

400 mg TP-271 q24 (n=6), a novel, broad spectrum tetracycline-class antibiotic or matching placebo (n=2) once daily for 7 days.

Drug: TP-271

Interventions

TP-271 DRUG

multiple oral doses of TP-271 or placebo, randomized 6:2, doses escalating 50 mg, 100 mg, 200 mg, 300 mg, 400 mg once daily for 7 days.

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 to 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 (HIV) types 1 and 2 and hepatitis B and C
• 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-childbearing potential, either 1-year postmenopausal or surgically sterile (i.e., 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 to 90 days after final administration 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 due to participation in the study, influence the results of the study, or influence the subject's ability to participate in the study
• Table 4 Acceptable Out-of-Range Clinical Laboratory Values
• Low Chemistry Values:
• Bicarbonate (a) Chloride GGT HDL cholesterol LDH LDL cholesterol Phosphorus
• High Chemistry Values:
• Chloride HDL cholesterol LDL cholesterol Phosphorus Triglycerides
• Out-of-Range Urinalysis Values; High or low specific gravity Cloudy Mucus Crystals Ketones (b) Hyaline casts High or low pH Urobilinogen (c)
• Out of Range Hematology Values; High hematocrit Basophils Monocytes MCV MCH MCHC RBC
• a Bicarbonate \>18 mEq/L. b 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 or any of the excipients in TP 271
• Clinically significant abnormality on a 12-lead ECG, which includes 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)

Sponsors & Collaborators

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

Study Sites (1)

PPD Phase I Clinic

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Bacterial Infections

Interventions

TP-271

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Study Officials

• Larry Tsai, MD

  Tetraphase Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Up to 5 cohorts of 8 subjects each will be enrolled. Subjects in each cohort will be randomized 6:2 to receive multiple oral doses of TP 271 at 1 of 5 ascending doses of TP-271 or placebo once or twice daily for 7 days, as shown in the table below. Every effort will be made to dose all subjects in a cohort on the same day. Proposed Oral Doses of Study Drug by Dose Cohort Cohort Dose Regimen Proposed Oral Dose A Once daily 50 mg TP-271 q24 (n = 6) or matching placebo (n = 2) B Once daily 100 mg TP-271 q24 (n = 6) or matching placebo (n = 2) C Once daily 200 mg TP-271 q24 (n = 6) or matching placebo (n = 2) D Once daily 300 mg TP-271 q24 (n = 6) or matching placebo (n = 2) E Once daily 400 mg TP-271 q24 (n = 6) or matching placebo (n = 2) Abbreviations: q24 = every 24 hours.

Study Record Dates

• First Submitted: February 16, 2018
• First Posted: March 1, 2018
• Study Start: March 20, 2018
• Primary Completion: December 31, 2018
• Study Completion: March 31, 2019
• Last Updated: December 17, 2021

Record last verified: 2021-12

Locations

US (1)