Pharmacokinetics, Pharmacodynamics and Safety of Basis in Acute Kidney Injury Study


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Primary Outcome Measures:

  • Maximum plasma concentration [Cmax] of NR [ Time Frame: 2 days ]

    Maximum plasma concentration [Cmax] of NR after oral administration of Basis

  • Maximum plasma concentration [Cmax] of pterostilbene [ Time Frame: 2 days ]

    Maximum plasma concentration [Cmax] of pterostilbene after oral administration of Basis

  • Area Under the Curve [AUC] of NR [ Time Frame: 2 days ]

    Area Under the Curve [AUC] of NR after oral administration of Basis

  • Area Under the Curve [AUC] of pterostilbene [ Time Frame: 2 days ]

    Area Under the Curve [AUC] of pterostilbene after oral administration of Basis

  • Incidence of Treatment-Emergent Adverse Events (Safety) [ Time Frame: 2 days ]

    Subjects will be interviewed to determine onset of nausea, abdominal pain, vomiting, diarrhea, or rash. Adverse events will be characterized as probably related, probably not related, or unknown

  • Incidence of Treatment-Emergent Laboratory Abnormalities (Safety) [ Time Frame: 2 days ]

    comprehensive metabolic panel (including liver function tests), complete blood count

Secondary Outcome Measures:

  • NAD+ levels [ Time Frame: 2 days ]

    To determine the increase in NAD+ levels in white blood cells (WBCs) following twice daily Basis administration

  • Dose finding for 50% increase in NAD+ levels in WBCs [ Time Frame: 2 days ]

    Dose of Basis that leads to 50% increase in NAD+ levels in WBC

  • Dose finding for 100% increase in NAD+ levels in WBCs [ Time Frame: 2 days ]

    Dose of Basis that leads to 100% increase in NAD+ levels in WBC

Acute kidney injury (AKI) is common, growing in incidence, and associated with significant morbidity and mortality. Sirtuins are anti-aging enzymes that play a diverse role in cellular energy metabolism and gene regulation. Mice deficient in SIRT1 are more susceptible to developing AKI and sirtuin activation is a potential treatment for AKI.

This is a randomized, double-blind, placebo-controlled, stepwise study of escalating doses of Basis (NR/pterostilbene) in patients with AKI. The study will potentially comprise up to four Steps. The purpose of the stepwise approach is to identify the dose of Basis that achieves at least a 50% and up to 100% increase in white blood cell (WBC) content of nicotinamide adenine dinucleotide (NAD+) without side-effects.

During each Step, Basis (5 patients) or placebo (1 patient) will be given twice a day for 2 days. Patients will have frequent blood sampling performed for a 24 hour period following dosing on Day 1 and then at 48 hr. The measurements in blood will include NR/pterostilbene blood concentrations and NAD+ and NAAD (nicotinic acid adenine dinucleotide) concentrations in WBCs.