A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single-Dose and Multiple-Dose Continuous Intravenous Infusions of TNP-2092 for Injection in Healthy Chinese Participants
Overview
- Phase
- Phase 1
- Intervention
- TNP-2092 for injection
- Conditions
- Acute Bacterial Skin and Skin Structure Infection (ABSSSI)
- Sponsor
- TenNor Therapeutics Inc.
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a phase 1, single-center, randomized, double-blind, placebo-controlled, dose-escalation clinical trial of single and multiple intravenous doses of TNP-2092 for injection in healthy Chinese participants.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Eighteen to 45 years of age, inclusive, of either gender.
- •A body weight of at least 50 kg (male participants) or 45 kg (female participants). A Body Mass Index (BMI) of between 18 to 28 kg/m2, inclusive.
- •Physical examinations, vital signs, and clinical laboratory tests are normal, or non-clinically significant abnormal judged by Investigator.
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria
- •History or clinical manifestations of significant central nervous system, cardiovascular, pulmonary, hepatic, renal, metabolic, other gastrointestinal, urological, endocrine or hematological disease that, in the opinion of the investigator, would confound the study results or compromise subject safety.
- •History or presence of alcohol or drug abuse, or illegal drug use.
- •Loss or donation of blood (\> 450 mL) within 3 months prior to the start of the Screening Period.
- •Any history of allergic drug reactions, or any contraindication to the use of rifampin/rifamycin or a fluoroquinolone.
- •Taking any medication known to induce or inhibit CYP enzymes within 28 days prior to screening.
- •Taking any prescribed or over-the-counter medications within 2 weeks prior to screening, or during the trial, including vitamins, food supplements, herbal remedies, or traditional Chinese remedies.
- •Significant abnormal findings on clinical laboratory tests, in the opinion of the Investigator, could jeopardize achieving the study objectives and/or compromise the participant's safety, including but not limited to:
- •Hematology: hemoglobin (HGB), white blood cell (WBC), absolute neutrophil count (ANC), or platelet count (PLT) \< the lower limit of normal (LLN).
- •Liver function: aspartate aminotransferase (AST) \> the upper limit of normal (ULN), and/or alanine aminotransferase (ALT) \> ULN, and/or total bilirubin \> ULN.
- •Renal function: serum creatinine \> ULN.
Arms & Interventions
200 mg single dose group (low-dose group)
Participants in the single-dose groups (200 mg in the low-dose group) were enrolled and received a single intravenous infusion of TNP-2092 for injection(Day 1) over 60 min (± 1 0 min).
Intervention: TNP-2092 for injection
200 mg single dose group (low-dose group)
Participants in the single-dose groups (200 mg in the low-dose group) were enrolled and received a single intravenous infusion of TNP-2092 for injection(Day 1) over 60 min (± 1 0 min).
Intervention: placebo
300 mg single and multiple dose continuous dose group (medium-dose group)
Participants in the single-dose, multiple-dose continuous dosing group (300 mg in the medium-dose group) received a single intravenous infusion of TNP-2092 for injection on Day 1 of the study. Subsequently, TNP-2092 for injection or placebo was administered as an intravenous infusion every 12 hours (q12 h, ± 10 min) daily on Study Days 4 to 10, and the last dose of TNP-2092 for injection was administered on the morning of Study Day 11.
Intervention: TNP-2092 for injection
300 mg single and multiple dose continuous dose group (medium-dose group)
Participants in the single-dose, multiple-dose continuous dosing group (300 mg in the medium-dose group) received a single intravenous infusion of TNP-2092 for injection on Day 1 of the study. Subsequently, TNP-2092 for injection or placebo was administered as an intravenous infusion every 12 hours (q12 h, ± 10 min) daily on Study Days 4 to 10, and the last dose of TNP-2092 for injection was administered on the morning of Study Day 11.
Intervention: placebo
400 mg single dose group (high-dose group)
Participants in the single-dose groups (400 mg in the high-dose group) were enrolled and received a single intravenous infusion of TNP-2092 for injection over 60 min (± 1 0 min)
Intervention: TNP-2092 for injection
400 mg single dose group (high-dose group)
Participants in the single-dose groups (400 mg in the high-dose group) were enrolled and received a single intravenous infusion of TNP-2092 for injection over 60 min (± 1 0 min)
Intervention: placebo
Placebo
Intervention: placebo
Outcomes
Primary Outcomes
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf)
Time Frame: 10, 20, 30, 45 minutes, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72 hours after the end of infusion
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma pharmacokinetic(PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Area Under the Plasma Concentration Versus Time Curve from 0 to the Last Measurable Concentration (AUC0-last)
Time Frame: 10, 20, 30, 45 minutes, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72 hours after the end of infusion
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma PK parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Maximum Observed Plasma Concentration (Cmax) of TNP-2092
Time Frame: 10, 20, 30, 45 minutes, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72 hours after the end of infusion
Plasma concentrations of TNP-2092 were measured by a specific and validated assay at specified time points
Percentage of Participants With Adverse Events (AEs)
Time Frame: Day 1 to Day 14
An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events.