NAVX-010-Phase I Tolerability and Pharmacokinetic Study in Healthy Male Subjects
Condition: Safety
Study type: Interventional
Phase: Phase 1

Summary: 
      This was a double-blind, placebo-controlled, randomized, single ascending dose, sequential
      group study. Each subject participated in only 1 treatment period.

      The primary objective was to determine the safety of single intramuscular (IM) injections of
      NAVX 010 in healthy subjects. The secondary objective was to determine the single dose
      pharmacokinetics (PK) of Gonyautoxin 2 (GTX 2) and Gonyautoxin 3 (GTX 3) following IM
      administration of NAVX 010 in healthy subjects.

      Thirty subjects were studied in 5 groups (Groups A to E); each group consisted of 6 subjects,
      of which 4 subjects received the Investigational Medicinal Product and 2 subjects received
      placebo. All subjects completed the study and data for all subjects were included in the
      safety analyses. A total of 20 subjects received NAVX-010 and were included in the PK
      population and subsequent PK analysis.
    

Detailed description: 
      This was a double-blind, placebo-controlled, randomized, single ascending dose, sequential
      group study. Each subject participated in only 1 treatment period.

      The primary objective was to determine the safety of single intramuscular (IM) injections of
      NAVX-010 in healthy subjects. The secondary objective was to determine the single dose
      pharmacokinetics (PK) of Gonyautoxin 2 (GTX 2) and Gonyautoxin 3 (GTX 3) following IM
      administration of NAVX-010 in healthy subjects.

      Thirty subjects were studied in 5 groups (Groups A to E); each group consisted of 6 subjects,
      of which 4 subjects received the Investigational Medicinal Product (IMP; NAVX-010) and 2
      subjects received placebo. All subjects completed the study and data for all subjects were
      included in the safety analyses. A total of 20 subjects received NAVX-010 and were included
      in the PK population and subsequent PK analysis.

      This study comprised healthy male subjects of any ethnic origin, aged between 18 and 45
      years, inclusive, and with a body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive.

      Dose levels of NAVX-010 were 2, 8, 25, 50, and 75 mcg. Doses were administered as IM
      injections into the deltoid muscle in the fasted state. The IMP was supplied in glass vials
      containing 1.2 mL solution at a total GTX 2 and GTX 3 concentration of 42 mcg/mL (at a
      relative epimer ratio of 62% GTX 2:38% GTX 3).

      Placebo was of identical appearance to the IMP, and was administered into the deltoid muscle
      in the fasted state.

      Single IM injections were administered in each group. Blood and urine samples were collected
      for the analysis of plasma and urinary concentrations of GTX 2 and GTX 3, and the following
      PK parameters for GTX 2 and GTX 3 were calculated: area under the concentration-time curve
      (AUC) from time 0 up to the time of last quantifiable plasma concentration (AUC0 t), AUC from
      time 0 to 24 hours postdose (AUC0-24), AUC from time 0 extrapolated to infinity (AUC0 ∞),
      percentage of AUC that is due to extrapolation from the time of last quantifiable
      concentration to infinity (%AUCextrap), maximum observed plasma concentration (Cmax), time of
      the maximum observed plasma concentration (tmax), time of last quantifiable plasma
      concentration (tlast), time before the start of absorption (tlag), apparent plasma terminal
      elimination half life (t½), apparent total plasma clearance (CL/F), apparent volume of
      distribution during the terminal elimination phase (Vz/F), amount of drug excreted in urine
      (Ae), percentage of dose excreted in urine (Fe), and renal clearance (CLR).

      Safety evaluations included adverse events (AEs), vital signs, 12 lead electrocardiogram
      (ECG), telemetry, clinical laboratory evaluations, physical examination, and clinical study
      questionnaires.
    

Intervention name(s): NAVX-010; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Dose levels of NAVX-010 were 2, 8, 25, 50, and 75 mcg. Four patients per active group. Each subject participated in only 1 treatment period.; There were two Placebos per group.
Other intervention name(s): Gonyautoxin 2/3; Placebo of NAVX-010
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: This was a double-blind, placebo-controlled, randomized, single ascending dose, sequential group study. Each subject participated in only 1 treatment period.
Masking: Double (Participant, Investigator)
Primary purpose: Other