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

T

Tetraphase Pharmaceuticals

Status and phase

Completed
Phase 1

Conditions

Bacterial Infections

Treatments

Drug: TP-271

Study type

Interventional

Funder types

Industry
NIH

Identifiers

NCT03450187
TP-271-004

Details and patient eligibility

About

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.

Full description

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.

Up to 5 cohorts of 8 subjects each (up to a total of 40 subjects) will be enrolled. Subjects in each cohort will be randomized 6:2 to receive multiple oral doses of TP 271 or placebo. Every effort will be made to dose all subjects in a cohort on the same day.

Doses of study drug will be administered orally either once daily in the morning or twice daily in the morning and evening from Days 1 to 7. In all subjects, the morning dose will be administered following an overnight fast (minimum 8 hours) of food and all beverages, except for water. For subjects in Cohorts D and E only, the evening dose will be administered following a minimum 3-hour fast of food and all beverages, except for water. Fasting in all cohorts will continue for at least 2 hours following each study drug administration.

During the Screening Period (within 28 days prior to the subject receiving study drug), each subject will be assessed for eligibility. Each subject must sign and date an ICF prior to undergoing any study-related procedures.

Enrollment

40 patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  1. Be within the age range of 18 to 50 years, inclusive, at the time of Screening
  2. 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
  3. Have a body mass index (BMI) ≥18.0 and ≤33.0 kg/m2
  4. Have a negative history of and negative screening results for human immunodeficiency virus (HIV) types 1 and 2 and hepatitis B and C
  5. Have the ability to communicate with the study unit staff in a manner sufficient to carry out all protocol procedures as described
  6. 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)
  7. 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

Exclusion criteria

  1. 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

  2. Clinical laboratory values that fall outside of the eligibility range specified in Appendix D are exclusionary; for clinical laboratory values that are not included in Appendix D, values outside of the reference range are exclusionary, except for those parameters listed in Table 4).

    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.

  3. Known allergy to tetracycline antibiotics or any of the excipients in TP 271

  4. 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)
    • 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 to be nonpathologic
  5. History of seizures

  6. History within 3 years of a positive result on a urine screen for drugs of abuse or a positive result on a urine screen at Screening for any of the following drugs of abuse: tetrahydrocannabinols, cocaine, opioids, phencyclidines, amphetamines, benzodiazepines, barbiturates, and cotinine

  7. Use of tobacco, nicotine, or nicotine-replacement products within 3 months prior to initial administration of study drug to the EOS Visit

  8. 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 of beer (12 oz), 1 glass of wine (approximately 4 to 5 oz), or distilled spirits (approximately 1 oz or 30 mL of liquor)

  9. Alcohol consumption within 48 hours prior to admission

  10. Participation in a clinical study within 10 half-lives of the prior study treatment or within the previous 3 months (if the half-life of investigational agent is unknown) prior to initial administration of study drug or planned participation in another clinical study concurrent with the present study

  11. History of difficulty donating blood or poor venous access

  12. Recent blood donation (1 unit or approximately 525 mL) within 1 month prior to receiving study drug or plans to donate prior to receiving study drug or during the clinical study

  13. Use of any prescription or nonprescription medication, including vitamins or herbal medications, vaccination, or immunization within 7 days or 5 half-lives (if known), whichever is longer, prior to initial administration of study drug, with the following exceptions: medications used to treat an AE are permitted, and the use of acetaminophen, naproxen, and ibuprofen is permitted, except for within 24 hours prior to dosing

  14. Male subjects who donate or plan to donate sperm during the study or within 90 days after final administration of the study drug

  15. Unwillingness or inability to follow the procedures outlined in the clinical study protocol

  16. Previous participation in another TP-271 study

Trial design

Primary purpose

Other

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

40 participants in 5 patient groups

Cohort A
Active Comparator group
Description:
50 mg TP-271 q24 (n=6), a novel, broad-spectrum tetracycline-class antibiotic or matching placebo (n=2) once daily for 7 days.
Treatment:
Drug: TP-271
Cohort B
Active Comparator group
Description:
100 mg TLP-271 q24 (n=6), a novel, broad spectrum tetracycline-class antibiotic or matching placebo (n=2) once daily for 7 days.
Treatment:
Drug: TP-271
Cohort C
Active Comparator group
Description:
200 mg TP-271 q24 (n=6), a novel, broad spectrum tetracycline-class antibiotic or matching placebo (n=2) once daily for 7 days.
Treatment:
Drug: TP-271
Cohort D
Active Comparator group
Description:
300 mg TP-271 q24 (n=6), a novel, broad spectrum tetracycline-class antibiotic or matching placebo (n=2) once daily for 7 days.
Treatment:
Drug: TP-271
Cohort E
Active Comparator group
Description:
400 mg TP-271 q24 (n=6), a novel, broad spectrum tetracycline-class antibiotic or matching placebo (n=2) once daily for 7 days.
Treatment:
Drug: TP-271

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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