A Phase 1, Open-label Pharmacokinetic Study of Intravenous NTM-001 (A Novel Formulation of Ketorolac Tromethamine Applied by Continuous Intravenous Infusion From A Pre-Mixed Bag) in Healthy Chinese Subjects
Overview
- Phase
- Phase 1
- Intervention
- Ketorolac Tromethamine
- Conditions
- Healthy Volunteers
- Sponsor
- Nuance Pharma (shanghai) Co., Ltd
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Cmax of NTM-001
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This will be a single center, open-label phase 1 study in healthy Chinese subjects. A total of up to 16 subjects may be enrolled to achieve a total target of 12 evaluable subjects. A full dose for NTM-001 will be defined as a 12.5 mg IV Loading Dose + 24-hour IV infusion (3.5 mg/hour).
Detailed Description
This will be a single center, open-label phase 1 study in healthy Chinese subjects. A total of up to 16 subjects may be enrolled to achieve a total target of 12 evaluable subjects. Subjects will remain in-house for the entire study. All subjects will be discharged at End-of-Study (EOS) on Day 5. A full dose for NTM-001 will be defined as a 12.5 mg IV Loading Dose + 24-hour IV infusion (3.5 mg/hour). Subjects who withdraw or are withdrawn from the study will not be replaced since attrition is considered. Blood will be collected for PK analysis. Safety assessments will include the following: adverse events (AEs), vital sign measurements, physical examinations, 12-lead electrocardiograms (ECGs), and clinical laboratory evaluations. infusion site reactions will be recorded as AEs.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject is a male or female Chinese with his/her biological parents and grandparents are of Chinese ethnicity, aged 18 to 45 years, inclusive at Screening.
- •Subject has a body mass index (BMI) between 19.0 and 24.0 kg/m2 at Screening and Baseline.
- •Subject has a body weight ≥50 kg at Screening and Baseline.
- •Subject is in good health, as determined by the Investigator, based on medical history, no findings of clinical significant abnormalities at physical examination, vital signs and clinical laboratory tests at Screening and Baseline.
- •Subject has normal renal function (CrCl ≥ 90 mL/min) as determined by Cockcroft Gault formula at Screening and Baseline.
- •Negative blood pregnancy test at Screening and negative urine test at Baseline for women of childbearing potential (WOCBP). For the purposes of this study, WOCBP is defined as: "All female subjects after puberty unless they are postmenopausal for at least 24 months, are surgically sterile for at least 6 months, or are sexually inactive for at least 6 weeks prior to first dose and throughout the study".
- •Subject is able to communicate well with the Investigator and is willing to comply with the requirements of the entire study.
- •Subject provides a written informed consent prior to the performance of any study procedure.
Exclusion Criteria
- •Subject has known hypersensitivity to ketorolac or any of the excipients in the Test or Reference formulations
- •There is evidence in the subject's medical history or in the medical examination or clinical laboratory results of any clinically significant hepatic, renal, gastrointestinal, cardiovascular, pulmonary, hematological or other significant acute or chronic abnormalities which might influence either the safety of the subject, interfere with trial procedures or outcomes, explicitly the absorption, distribution, metabolism or excretion of the active agent under investigation.
- •Subjects who smoked more than 5 cigarettes per day during the 3 months prior to screening or did not agree to refrain from using any tobacco products during the study period.
- •Subject has significant acute or chronic infections, including, among others:
- •Known history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome or HIV antibody positive.
- •Hepatitis B virus (HBV) surface antigen positive or Hepatitis C virus (HCV) antibody positive.
- •Active tuberculosis (history of exposure or history of positive tuberculin test, plus, presence of clinical symptoms, physical or radiographic findings). If the Investigator suspects a potential risk history for tuberculosis, the physician may use the Quanteferon® test to omit the risk.
- •Subject has chronic malnutrition or severe hypovolemia.
- •Subject is pregnant or breastfeeding. Pregnancy status will be confirmed by serum assay for qualitative human chorionic gonadotropin (hCG) at Screening and urine assay at Baseline for females of child-bearing potential.
- •Subject has a positive test result for amphetamines including methylenedioxymethamphetamine and methamphetamine, barbiturates, benzodiazepines, cocaine, marijuana (THC), opioids including opiates and methadone or alcohol (blood) at Screening or Baseline.
Arms & Interventions
NTM-001 Treatment Arm
NTM-001 loading dose of 12.5 mg administered over approximately 60 seconds, followed by a continuous IV infusion at a rate of 3.5 mg/h for 24h, by a pre-programmed infusion pump.
Intervention: Ketorolac Tromethamine
Outcomes
Primary Outcomes
Cmax of NTM-001
Time Frame: 0 to 96 hours
Maximum observed plasma concentration (Cmax).
AUC0-t of NTM-001
Time Frame: 0 to 96 hours
Area under the plasma concentration-versus-time curve from time 0 to the last collection time after drug administration with a concentration equal to or greater than the lower limit of quantification (AUC0-t).
AUC0-∞ of NTM-001
Time Frame: 0 to 96 hours
Area under the plasma concentration-versus-time curve from time 0 extrapolated to infinity after drug administration (AUC0-∞).
Tmax of NTM-001
Time Frame: 0 to 96 hours
Time to maximum observed plasma concentration (Tmax).
t1/2 of NTM-001
Time Frame: 0 to 96 hours
Apparent terminal elimination half-life (t1/2).