Safety, Tolerability and Pharmacokinetics of Inhaled Nanoparticle Formulation of Remdesivir (GS-5734) and NA-831
- Conditions
- Severe Acute Respiratory Syndrome of Upper Respiratory TractCovid19Severe Acute Respiratory SyndromeSevere Acute Respiratory InfectionNeurodegenerationCorona Virus InfectionNeuroinflammatory ResponseSevere Acute Respiratory Syndrome (SARS) Pneumonia
- Interventions
- Drug: Placebo- 0.10 mg/kgDrug: Placebo- 1.00 mg/kgDrug: Placebo- 2.00 mg/kgDrug: Placebo- 0.20 mg/kgCombination Product: Placebo 0.20 mg + 2.00 mg/kgCombination Product: Placebo 0.10 mg + 1.00 mg/kg
- Registration Number
- NCT04480333
- Lead Sponsor
- Biomed Industries, Inc.
- Brief Summary
The clinical study is designed to evaluate the safety, tolerability and pharmacokinetics of inhaled nanoparticle nanoparticle formulation of Remdesivir (GS-5734) alone and in combination with NA-831 in 48 healthy volunteers.
- Detailed Description
It has been discovered that SARS-CoV-2 viruses (Covid-19) can directly invade the nervous system of patients, instead of injuring the nervous system through the immune response. Neurotropism is one common feature of Covid-19. Such neuro-invasive propensity of Covid-19 has been documented almost for all the Beta-coronaviruses including SARS-CoV and MERS-CoV.
Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. It was observed that patients surviving COVID-19 are at high risk for subsequent development of neurological disease and in particular Alzheimer's disease.
NA-831 is a new neuroprotective and neurogenesis drug that has been demonstrated its promising safety and efficacy in Phase 2A for the treatment of early onset of Alzheimer's disease. NA-831 in oral formulation is well tolerated NA-831 with no adverse effects. NA-831 in oral formulation exhibits predictable pharmacokinetics including dose-dependent exposure linearity and low variability.
Based on animal studies, NA-831 can provide effective interventions during the severe acute respiratory syndrome, and provide appropriate rehabilitation measures afterwards.
Remdesivir (GS-5734) intravenous formulation has been approved by the FDA under the emergency use authorization for potential treatment of severe cases of Covid-19.
It was found the upper respiratory tract is the most prevalent site of SARS-CoV-2 infection early in disease. Delivering drugs directly to the primary site of infection with a nebulizer, inhaled nanoparticle formulation may enable more targeted and accessible administration in non-hospitalized patients and potentially lower systemic exposure to the drug.
The study is designed to evaluate the safety, tolerability and pharmacokinetics of a new nanoparticle formulation of Remdesivir (GS-5734) and combination therapy with NA-831 in healthy volunteers.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 45
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Comparable Placebo- 0.10 mg/kg Placebo- 0.10 mg/kg 3 subjects will take inhaled formulation of placebo once a day for 5 days Comparable Placebo- 1.00 mg.kg Placebo- 1.00 mg/kg 3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days Comparable Placebo - 2.00 mg/kg Placebo- 2.00 mg/kg 3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days Comparable Placebo- 0.20 mg/kg Placebo- 0.20 mg/kg 3 subjects will take inhaled formulation of placebo once a day for 5 days Placebo- 0.20 mg/kg + 2.00mg/kg Placebo 0.20 mg + 2.00 mg/kg 3 Subjects- inhaled formulation of placebo once/day for 5 days Placebo- 0.10- mg/kg placebo+1.00 mg mg/kg Placebo 0.10 mg + 1.00 mg/kg 3 Subjects - inhaled formulation of placebo once/day for 5 days
- Primary Outcome Measures
Name Time Method Proportion of Participants Experiencing any Treatment-Emergent Adverse Events First dose date up to Day 30 Follow-up Assessment AEs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) V5.0
Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities First dose date up to Day 30 Follow-up Assessment This will be assessed at various time points by clinical laboratory tests and vital signs.
- Secondary Outcome Measures
Name Time Method AUC calculated from time of administration to the last measurable concentration (AUC0-last) - Pharmacokinetic Assessment 7 days Monitoring of the levels of drugs in subject sera at various time points to elucidate the area under the curve from time of administration to the last measurable of NA-831 and GS-5734
Maximum Concentration (Cmax) - Pharmacokinetic Assessment 7 days Monitoring of the levels of drugs in subject sera at various time points to elucidate the maximum concentration (Cmax) of NA-831 and GS-5734 in human serum.
Time to Maximum Concentration (Tmax) - Pharmacokinetic Assessment 7 days Monitoring of the levels of drugs in subject sera at various time points to elucidate the time to maximum concentration (Tmax) of NA-831 and GS-5734 in human serum
Area Under the Curve Extrapolated to Infinity (AUC0-∞) 7 days Monitoring of the levels of drugs in subject sera at various time points to elucidate the area under the curve extrapolated to infinity (AUC0-∞) of NA-831 and GS-5734
Half-Life (t1/2) - Pharmacokinetic Assessment 7 days Monitoring of the levels of drugs in subject sera at various time points to elucidate the half-life (t1/2) of NA-831 and GS-5734 in human serum.
Volume of Distribution (Vd) - Pharmacokinetic Assessment 7 days Monitoring of the levels of drugs in subject sera through various time points to elucidate the volume of distribution (Vd) of NA-831 and GS-5734 in human serum.
Clearance [CL] - Pharmacokinetic Assessment 7 days Monitoring of the levels of drugs in subject sera through at various time points to elucidate clearance \[CL\] of NA-831 and GS-5734 in human serum.
Trial Locations
- Locations (1)
Coronavirus Research Institute
🇺🇸Sunnyvale, California, United States