A Phase 1, Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Intravenous TP-271 in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- TP-271
- Conditions
- Bacterial Infections
- Sponsor
- Tetraphase Pharmaceuticals, Inc.
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Adverse Events
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Detailed Description
Up to 5 cohorts of 8 subjects each (up to a total of 40 subjects) will be enrolled. The 8 subjects within each cohort will be randomized 6:2 to receive multiple IV doses of TP-271 or placebo. Study drug will be administered IV once daily on the morning of Days 1 through 7 following an overnight fast (minimum 8 hours). The planned doses for study drug for Cohorts A - E are 0.5 mg/kg TP-271 or placebo, 1.0 mg/kg TP-271 or placebo, 2.0 mg/kg TP-271 or placebo, 2.5 mg/kg TP-271 or placebo and 3.0 mg/kg TP-271 or placebo respectively. During the Screening period (Days -28 to -2 prior to the subject receiving TP-271 or placebo), each subject will be assessed for eligibility. Each subject must sign and date the ICF prior to undergoing any study-related procedures. All cohorts will follow the same study design. On Day -1, subjects will be admitted to the study unit and eligibility confirmed. On Day 1, eligible subjects will be enrolled and randomized to receive either TP-271 or placebo and will receive the assigned drug from Days 1 through 7. Subjects will be required to stay at the study unit from Days -1 through 11 to assess safety and obtain the required PK samples. On Day 11, subjects will be discharged from the study unit. A final safety assessment will be performed once between Days 14 and 20, 7 to 13 days following administration of the subject's final dose of study drug. After all 8 subjects in a cohort have completed study procedures through Day 11, the Principal Investigator and the Sponsor's Medical Monitor will evaluate all blinded safety and plasma PK data to determine whether any criteria that would require a meeting of the Safety Monitoring Committee (SMC) are met. If no such criteria are met, the study may proceed to the subsequent cohort at the next higher dose of TP-271 without consulting the SMC.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
- •Clinical laboratory values that fall outside the eligibility range specified in Appendix D; for laboratory values that are not included in Appendix D, values outside the reference range are exclusionary, with the following exceptions (Table
- •Acceptable Out-of-Range Clinical Laboratory Values
- •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
Arms & Interventions
Cohort A
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
Intervention: TP-271
Cohort A
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
Intervention: Placebo
Cohort B
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
Intervention: TP-271
Cohort B
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
Intervention: Placebo
Cohort C
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
Intervention: TP-271
Cohort C
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
Intervention: Placebo
Cohort D
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
Intervention: TP-271
Cohort D
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
Intervention: Placebo
Cohort E
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
Intervention: TP-271
Cohort E
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
Intervention: Placebo
Outcomes
Primary Outcomes
Adverse Events
Time Frame: Throughout the study, ~ 49 days
Incidence, intensity, and type of adverse events (AEs) from the time of signing the informed consent form (ICF) through the EOS Visit
Vital Signs
Time Frame: ~ 20 days
Changes in vital signs from Day -1 through the EOS Visit
Safety Laboratory Results
Time Frame: ~ 20 days
Changes in safety laboratory (clinical chemistry, electrolytes, hematology, blood glucose, and coagulation) results from Day -1 through the EOS Visit
Physical Exams
Time Frame: ~ 20 days
Changes in physical examination findings between Day -1 and the EOS Visit
ECG measurements
Time Frame: ~ 20 days
Changes in electrocardiogram (ECG) measurements from Day -1 through the EOS Visit
Secondary Outcomes
- Assess the Pharmacokinetics (PK) of TP-271 in Urine(~11 days)
- Assess the Pharmacokinetics (PK) of TP-271in Plasma(~11 days)