A Phase 1 Study to Assess the Safety, Tolerability and PK of IV TP-271

Exclusion Criteria

• •1. History and/or presence of any clinically significant disease or disorder such as cardiovascular, pulmonary, renal, hepatic, neurological, gastrointestinal, and psychiatric/mental disease/disorders, which, in the opinion of the PI, 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.
• •2. Clinical laboratory values that fall outside the eligibility range specified in the table in Appendix C are exclusionary. For the laboratory values that are not included in Appendix C, values outside of the reference range are exclusionary with the following exceptions:
• •Low Chemistry Values High Chemistry Values Out of Range UA Out of Range Hematology Bicarbonate (\> 18 mEq/L Chloride GGT HDL Cholesterol LDH LDL Cholesterol Phosphorus Triglycerides Chloride HDL Cholesterol LDL Cholesterol Phosphorus Triglycerides High or low specific gravity Cloudy Mucus Crystals Ketones (when blood glucose is normal) Hyaline casts High or low pH
• •High hematocrit Basophils Monocytes MCV MCHC MCH RBC
• •3. Blood pressure and pulse outside of the following ranges are exclusionary:
• •* Systolic blood pressure 85 - 145 mm Hg
• •* Diastolic blood pressure 50 - 95 mm Hg
• •* Pulse rate 45 - 95 beats per minute (bpm)
• •4. Known allergy to tetracycline antibiotics or to any of the excipients in TP-271.
• •5. Clinically significant abnormal 12-lead ECG, including the following:
• •* Rhythm other than sinus, QTc interval using Fridericia's formula (QTcF) \>450 msec;
• •* Evidence of second- or third-degree atrioventricular (AV) block;
• •* Pathological Q-waves (defined as Q-wave \>40 msec or depth \>0.4 to 0.5 mV);
• •* Evidence of ventricular pre-excitation;
• •* Electrocardiographic evidence of complete left bundle branch block, right bundle branch block (RBBB), incomplete LBBB;
• •* Intraventricular conduction delay with QRS duration \>120 msec;
• •* ST segment abnormalities unless judged by the Investigator to be non-pathologic.
• •6. History of seizures.
• •7. A history within 3 years of Screening of drug abuse (including benzodiazepines, opioids, amphetamine, and cocaine) or a positive drug result at Screening for any of these drugs of abuse. Also excluded are subjects who test positive for cannabinoids (THCs).
• •8. Use of tobacco, nicotine, or nicotine-replacement products within the 3 months prior to the dose of study drug through the last study visit.
• •9. Typical weekly alcohol consumption of 7 or more alcoholic drinks. One drink is defined as 1 glass of beer (approximately 10 to 12 oz) or 1 can (12 oz) of beer, 1 glass of wine (approximately 4 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).
• •10. Alcohol consumption within 48 hours prior to dosing.
• •11. Participation in a clinical trial within 10 half-lives of the prior study treatment or the past 3 months if the half-life is unknown of dose or planned participation in another trial in addition to this one during the trial.
• •12. History of difficulty in donating blood or poor venous access.
• •13. Subject has donated blood (1 unit or 350 mL) within 1 month prior to receiving test material or plans to donate prior to receiving test material or during the trial.
• •14. Use of 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. The use of acetaminophen, naproxen, and ibuprofen is permitted except for within 24 hours prior to dosing. (Note: Subjects must refrain from taking herbal or dietary supplements or prescription drug therapy for the duration of the study.)
• •15. Unwillingness or inability to follow the procedures outlined in the protocol. Subject is mentally or legally incapacitated