A study in healthy males to assess the safety and tolerability of two different formulations of the study drug, (MSP-2017), administered intranasally.

Study Treatments/Medications: There will be two active formulations. All formulations will be administered by the intranasal route. Active Test Formulations: The active investigational product (API) is (-)-MSP-2017 (code-named MSP-2017). The two Active Test Formulations (MSP-2017A and MSP-2017B) are the API formulated in two different, but closely related, aqueous solutions: MSP-2017A: water, MSP-2017, acetic acid, n-dodecyl-D-maltoside, disodium EDTA, sulfuric acid. MSP-2017B: water, MSP-2017, acetic acid, disodium EDTA, sulfuric acid. Single doses of both MSP-2017A and MSP-2017B will be evaluated at ascending concentrations with subsequent cohorts, but doses will not alter within a cohort. The starting doses for both MSP-2017A and MSP-2017B will be 3.5 mg (nominal 0.05 mg/kg based on 70 kg subject). Each subject in each dose level cohort will receive two single doses of either both active drugs or both placebos. Within each cohort, the eight subjects will be randomly assigned to one of four groups. For those assigned active drug: N=3: Active MSP-2017A and Active MSP-2017B N=3: Active MSP-2017B and Active MSP-2017A Doses will be escalated sequentially through the cohorts. The starting dose and incremental dose increase through the cohorts will be determined based on the results of the preclinical studies. Before the subsequent cohort of eight subjects can be enrolled and dosed at the next highest dose level, feasibility of escalation will be evaluated based on safety observations from the previous, lower dose level. Evaluation will be a full safety review by the Safety Evaluation Committee (SEC), which will include at least one certified cardiologist, the Principal Investigator and the Sponsor’s Medical Monitor after each dosing cohort is complete. It is intended that at no time will a dose be increased by more than twice that of the previous dose. However, a greater increase may be permitted if there are no detectable plasma concentrations of MSP-2017 or there is no effect on the pharmacodynamic parameters, provided the greater increase is deemed to be safe by the SEC. Dose escalation is planned to be identical for both MSP-2017 formulations, however, the data will be reviewed independently for each MSP-2017 formulation and the SEC may allow deviation from the planned dose escalation schedule for either MSP-2017 formulations independently in response to the results from each cohort. If = 2 subjects administered a dose of one of the MSP-2017 formulations experience a clearly determined DLT at that dose level, dosing must cease with that formulation and the MTD for that MSP-2017 formulation will be determined. However, the SEC may deem it safe to continue dose escalation with the second MSP-2017 formulation for subsequent cohort(s) of eight subjects with six subjects receiving that MSP-2017 formulation and two receiving a single dose of the matched Placebo. Dose escalation will proceed until two or more of six active (drug) subjects experience a DLT or until dose level #6 is achieved. However, if the maximum tolerated dose (MTD) is not achieved for each or one of the MSP-2017 formulations after six dose levels, an additional two cohorts (i.e., 16 subjects) will be enrolled, resulting in a total of 64 subjects enrolled in the study. The MTD for that active drug will be considered the dose level immediately below the dose at which two of six subjects who received the MSP-2017 formulation experienced a DLT. If no DLT occurs, the MTD for the active drug(s) will be declared as the highest dose evaluated. Subjects will be randomly assigned to one of four groups within each cohort which will involve administration of a single intranasal dose on Day 1 (right nostril) and Day 3 (left nostril), when possible depending on dose level, of either MSP-2017A then MSP-2017B, or MSP-2017B then MSP-2017A, or Placebo A then Placebo B or Placebo B then Placebo A.