A Phase 1, Open-Label Study to Assess the Single-Dose Pharmacokinetics of Eravacycline in Subjects With End Stage Renal Disease and Healthy Subjects
A Phase 1, Open-Label Study to Assess the Single-Dose Pharmacokinetics of Eravacycline in Subjects With End Stage Renal Disease and Healthy Subjects
This is a multi-center, open-label clinical study to assess the single-dose PK of
 eravacycline in subjects with renal impairment and healthy subjects conducted at
 approximately 2 sites in the United States. This study includes an up to 21-day Screening
 Period, a 5-day Treatment Period, and an End of Study Visit occurring approximately 2 weeks
 (±2 days) after study drug administration. Approximately 12 subjects will be enrolled: 6
 subjects with ESRD and 6 healthy subjects with normal renal function. Healthy subjects will
 be matched to renally impaired subjects in gender, age, and body mass index (BMI). All
 subjects will be administered a single IV dose of eravacycline (1.5 mg/kg).
Inclusion Criteria:

 1. Male or female subject aged 18 years at Screening;

 2. Eligible female subjects of childbearing potential with a non-sterilized male sexual
 partner must agree to use 2 medically accepted, effective methods of birth control
 (eg, hormonal contraceptive, barrier contraceptive with additional spermicide, or an
 intrauterine device) beginning >30 days prior to study drug administration and
 continuing until 7 days after the end of the study. Female subjects who are
 postmenopausal must have been postmenopausal for >1 year if they wish not to use
 contraceptives. If postmenopausal status is questionable, the subject's follicle
 stimulating hormone level must be checked and must be elevated and consistent with
 postmenopausal levels (ie, >40 IU/L); otherwise these subjects must agree to use
 contraceptives listed above;

 3. Male subjects with sexual partners of childbearing potential must agree to use a
 barrier contraceptive from the time of study drug administration through 7 days after
 the end of the study;

 4. Female subjects of childbearing potential (including females with questionable
 postmenopausal status) must have a negative pregnancy test prior to dosing (Screening
 and Day -1);

 5. Has a body mass index of 17 kg/m2 to 40 kg/m2, inclusive;

 6. Has negative alcohol and illicit drug screens;

 7. Has a negative screen for Human Immunodeficiency Virus;

 8. Is able to understand and comply with study procedures and give written informed
 consent according to institutional and regulatory guidelines;

 Subjects with ESRD renal impairment:

 9. Has a positive diagnosis of ESRD maintained on hemodialysis treatments 3 times a week
 for at least 3 months with a minimum Kt/V of 1.2;

 10. Is otherwise considered healthy except for abnormalities consistent with underlying
 ESRD as determined by past medical history, physical examination, vital signs, and
 laboratory tests at Screening;

 Healthy subjects without renal impairment:

 11. Must be in good health as determined by screening medical history, physical
 examination, vital signs, blood chemistry, hematology, glucose, and coagulation
 performance at Screening;

 12. Has a negative screen for hepatitis B (HBV) and hepatitis C (HCV); and

 13. Should be matched to a subject with renal impairment in gender, age, and BMI.

 Exclusion Criteria:

 1. Female subjects who are pregnant, breastfeeding, or planning to become pregnant during
 the course of the study;

 2. Has a history or current evidence of clinically significant hematological, hepatic,
 endocrine, pulmonary, gastrointestinal, cardiovascular, neurological, or psychiatric
 disease that may pose a significant safety risk or diminish a subject's ability to
 undergo all study procedures and assessments;

 3. Use of another investigational drug or device within 30 days prior to receiving
 eravacycline (TP-434), or within at least 5 half-lives of the previous investigational
 drug, whichever is longer;

 4. Has a history of alcoholism or drug abuse within 6 months prior to dosing;

 5. Has urinary incontinence;

 6. Has a typical weekly alcohol consumption of 14 alcoholic drinks. One drink is defined
 as 1 glass of beer (approximately 10 oz to 12 oz) or 1 can (12 oz) of beer, 1 glass of
 wine (approximately 4 oz to 5 oz), or 1 glass of distilled spirits (hard liquor)
 containing 1 oz of the liquor (1 oz of liquid is approximately 30 mL);

 7. Use of alcohol within 48 hours prior to admission until completion of the final PK
 draw on Day 5;

 8. Has had a major surgical procedure within 3 months prior to administration of study
 drug;

 9. Has known allergies to tetracycline antibiotics or related compounds, or a history of
 multiple adverse drug allergies of any origin;

 10. Has inadequate venous access;

 11. Donated >500 mL of blood within 2 months prior to Screening;

 12. Is a member of the clinical site personnel directly affiliated with this study;

 13. Has poor mental function or any other reason to expect subject difficulty in complying
 with the requirements of the study in the judgment of the investigator;

 14. Has any surgical or medical condition which might significantly alter the absorption,
 distribution, or excretion of the drug;

 15. Fails to comply with protocol requirements, or whose further participation in the
 study would be unsuitable to the subject, as determined by the investigator;

 16. Clinically significant abnormal electrocardiograms (ECGs) (QTcF >500 msec);

 17. Has clinically significant abnormal laboratory value(s), other than those consistent
 with stage 5 chronic kidney disease. Aspartate aminotransferase or alanine
 aminotransferase >1.5 × the upper limit of the reference range or total bilirubin >1.5
 × the upper limit of the reference range. A single repeat is allowed for eligibility
 determination;

 18. Unwillingness to refrain from liquids or food containing grapefruit, cranberry,
 caffeine, or other xanthines from 96 hours prior to admission until completion of the
 final PK draw on Day 5;

 19. Unwillingness to refrain from eating foods containing poppy seeds for 48 hours before
 admission until completion of the final PK draw on Day 5;

 20. Unwillingness to abstain from any unaccustomed strenuous exercise or contact sports
 for at least 72 hours prior to the Screening Visit and 72 hours prior to admission on
 Day -1 until discharge from the study;

 Subjects with ESRD renal impairment:

 21. Has active HCV or HBV and is receiving antiviral therapy (either prescribed or
 herbal);

 22. Has fluctuating or rapidly deteriorating renal function as indicated by clinical
 and/or laboratory signs of renal impairment;

 23. Has signs of active infection;

 24. Takes any herbal concomitant medication within 7 days, or 5 half-lives (if known),
 whichever is longer, prior to dosing and within 24 hours after dosing, excluding
 hormonal contraceptives;

 Subjects without renal impairment:

 25. Has systolic blood pressure outside of the range of 90-160 mmHg, or diastolic blood
 pressure outside the range of 45-100 mmHg, or heart rate outside the range of 50 100
 bpm for female subjects or 45-100 bpm for male subjects;

 26. Has a history of Gilbert's disease; or

 27. Takes any concomitant medication, either prescribed or over the counter. This includes
 any prescription or non-prescription medication, including vitamins or herbal
 medications, within 7 days, or 5 half-lives (if known), whichever is longer, prior to
 dosing and within 24 hours after dosing, excluding hormonal contraceptives. The use of
 acetaminophen, naproxen, and ibuprofen is permitted except for within 24 hours prior
 to dosing.