None listed
Conditions
Brief summary
This study has its objectives: To evaluate the safety and tolerability of multiple oral doses of NPI-001 Tablets in healthy adult subjects; To evaluate the effect of food on the pharmacokinetics (PK) of NPI-001 following single doses, 1500 mg and 750 mg, in the fed versus fasted state; To characterize the pharmacokinetics of NPI-001 following multiple doses over 5 days, fed; To evaluate the effect of NPI-001 on potential biomarkers of the pharmacodynamic effect (protein carbonyls, GSH/GSSG, cysteine/cystine (Cys/Cys-Cys)). Study design: This randomized, double-blinded, cross-over study will include an evaluation of PK of NPI-001 in fed versus fasted healthy volunteers followed by a 5-day dosing period to ascertain if multiple doses of NPI-001 can alter GSH and CYS levels in plasma. Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to first dose administration. Subjects will be resident in the clinical facility from the evening prior to first dose (Day -1) until discharge on Day 10. A post-dose follow up visit will occur at Day 15. On Day 1 and Day 3, each subject will receive a single oral dose of NPI-001 or Placebo. The dose levels of NPI-001 will be 1500 mg for Cohort 1 (6 tablets), and 750 mg for Cohort 2 (3 tablets). Dosing on Days 1 and 3 will be a placebo-controlled, balanced, two-treatment two-sequence randomized fasted/fed crossover design, as follows: • 8 subjects in each cohort (6 NPI-001, 2 placebo) will be dosed on Day 1 following a 10 hour overnight fast and on Day 3 following a high fat breakfast [Fasted-Fed]. • 8 subjects in each cohort (6 NPI-001, 2 placebo) will be dosed on Day 1 following a high fat breakfast and on Day 3 following a 10 hour overnight fast [Fed-Fasted]. On Days 5-9, all subjects will receive NPI-001 or placebo three times per day, at approximately 8am (following a standard breakfast), 2pm and 8pm, with the last dose on the morning of Day 9. The dose levels of NPI-001 will be 500 mg per dose for Cohort 1 (2 tablets), and 250 mg per dose for Cohort 2 (1 tablet). Safety measures monitored throughout the study will include adverse events and use of concomitant medication, vital signs, and clinical laboratory tests. Blood samples for assessment of PK will be collected on Days 1, 3 and 9, at pre-dose, then at 0.25, 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10 and 12 hours post-dose, and on Days 2, 4 and 10 at 24 hours post-dose. Blood samples for assessment of PD will be collected on Days 1 and 3 at pre-dose and 1 hour post-dose, on Day 9 at 1 hour post-dose, and at the follow-up visit.
Interventions
This randomized, double-blinded, cross-over study will include an evaluation of the Pharmacokinetics of NPI-001 in fed versus fasted healthy volunteers followed by a 5-day dosing period to ascertain if multiple doses of NPI-001 can alter Glutathione and Cysteine levels in plasma.
Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to first dose administration. Subjects will be resident in the clinical facility at CMAX, Adelaide from the eveni
This randomized, double-blinded, cross-over study will include an evaluation of the Pharmacokinetics of NPI-001 in fed versus fasted healthy volunteers followed by a 5-day dosing period to ascertain if multiple doses of NPI-001 can alter Glutathione and Cysteine levels in plasma. Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to first dose administration. Subjects will be resident in the clinical facility at CMAX, Adelaide from the evening prior to first dose (Day -1) until discharge on Day 10. A post-dose follow up visit will occur at Day 15. On Day 1 and Day 3, each subject will receive a single oral dose of NPI-001 or Placebo. The dose levels of NPI-001 will be 1500 mg for Cohort 1 (6 tablets), and 750 mg for Cohort 2 (3 tablets). Dosing on Days 1 and 3 will be a placebo-controlled, balanced, two-treatment two-sequence randomized fasted/fed crossover design, as follows: • 8 subjects in each cohort (6 NPI-001, 2 placebo) will be dosed on Day 1 following a 10 hour overnight fast and on Day 3 following a high fat breakfast [Fasted-Fed]. • 8 subjects in each cohort (6 NPI-001, 2 placebo) will be dosed on Day 1 following a high fat breakfast and on Day 3 following a 10 hour overnight fast [Fed-Fasted]. The high fat breakfast will consist of: 2 eggs fried in butter, 2 strips bacon. 2 slices of toast with butter, 4 oz hash brown potatoes fried in butter 8 oz (240 mL) whole milk. This high fat meal contains the equivalent of approximately 150 protein calories, 250 carbohydrate calories, and 500 to 600 fat calories. For the high fat meal, subjects should commence the recommended meal approximately 30 minutes prior to administration of the study drug. Although study subjects should consume this meal in less than or equal to 30 minutes, the drug product should be administered approximately 30 minutes after starting the meal and at least 80% of the meal should be finished promptly. The following measures will be employed to ensure treatment and high fat meal compliance: All study drug doses and high fat meals will be administered under the supervision of suitably qualified study site staff Immediately after dose administration, visual inspection of the mouth and hands will be performed for each subject At each dosing occasion, a predose and postdose inventory of IMP and placebo will be performed on the dose containers. Subjects will be monitored throughout the trial for adherence to the protocol by CMAX staff. All deviations from the protocol will be recorded by staff on duty at the time and logged in the eCRF for the study. Quality control and quality assurance will be performed according to CMAX Clinical Research standard operating procedures (SOPs) On Days 5-9, all subjects will receive NPI-001 or placebo three times per day, at approximately 8am (following a standard breakfast), 2pm and 8pm, with the last dose on the morning of Day 9. The dose levels of NPI-001 will be 500 mg per dose for Cohort 1 (2 tablets), and 250 mg per dose for Cohort 2 (1 tablet). Safety measures monitored throughout the study will include adverse events and use of concomitant medication, vital signs, and clinical laboratory tests. Blood samples for assessment of PK will be collected on Days 1, 3 and 9, at pre-dose, then at 0.25, 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10 and 12 hours post-dose, and on Days 2, 4 and 10 at 24 hours post-dose. Blood samples for assessment of PD will be collected on Days 1 and 3 at pre-dose and 1 hour post-dose, on Day 9 at 1 hour post-dose, and at the follow-up visit.
Sponsors
Nacuity Pharmaceuticals Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects must satisfy all of the following criteria at the Screening Visit unless otherwise stated: 1. Males or females, of any race, between 18 and 60 years of age, inclusive. 2. Body mass index between 18.0 and 32.0 kg/m2, inclusive. 3. In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations at Screening or Check-in as assessed by the Investigator (or designee). 4. Females will be nonpregnant and nonlactating, and females of childbearing potential and males will agree to use contraception. 5. Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions.
Exclusion criteria
Subjects will be excluded from the study if they satisfy any of the following criteria at the Screening visit, unless otherwise stated: 1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee). 2. History of significant hypersensitivity to any drug compound, food, or other substance, unless approved by the Investigator (or designee). 3. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs, including cholecystectomy (uncomplicated appendectomy and hernia repair will be allowed). 4. History of alcohol abuse or drug/chemical abuse per the Diagnostic and Statistical Manual of Mental Disorders-IV criteria within 2 years prior to Check in. 5. Alcohol consumption of >21 units per week for males and >14 units for females. 6. Positive urinary drug screen (confirmed by repeat, if necessary) at Screening (does not include alcohol) or Check in (does include alcohol breath test). 7. Liver function test values >1.5 upper limit of normal (ULN) (excluding isolated hyperbilirubinemia) or QTcF >450 milliseconds. 8. Positive hepatitis panel and/or positive human immunodeficiency test. Subjects whose results are compatible with prior immunization and not infection may be included at the discretion of the Investigator. 9. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half lives, whichever is longer, prior to Check in. 10. Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John’s Wort, within 30 days or 5 half-lives (whichever is longer) prior to Check in, unless deemed acceptable by the Investigator (or designee). 11. Use or intend to use any prescription medications/products other than oral, implantable, transdermal, injectable, or intrauterine contraceptives, or hormone replacement therapy, within 14 days prior to Check in, unless deemed acceptable by the Investigator (or designee). 12. Use or intend to use any nonprescription medications/products (excluding paracetamol, which is allowed), vitamins, minerals, antioxidant supplements (e.g., acetylecysteine-related, cysteine-related or glutathione-related substances, etc.) and phytotherapeutic/herbal/plant derived preparations within 7 days prior to Check in, unless deemed acceptable by the Investigator (or designee). 13. Use of tobacco or nicotine containing products within 3 months prior to Check in and positive urine cotinine test at screening or check-in. 14. Receipt of blood products within 2 months prior to Check in. 15. Donation of blood from 30 days prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening. 16. Poor peripheral venous access. 17. Have previously completed or withdrawn from this study or any other study investigating NPI 001 or NACA, and have previously received the investigational product. 18. Subjects who, in the opinion of the Investigator and/or Sponsor (or designee), should not participate in this study. 19. An employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, sibling, or child, whether biological or legally adopted.
Outcome results
None listed