Pharmacokinetics (PK) Study of Epinephrine Inhalation Aerosol in Healthy Volunteers

• Vital Signs [ Time Frame: at baseline, and at 10, 30, 60, 120, 180, and 360 min post-dose. ] [ Designated as safety issue: Yes ]
  Vital signs, i.e., blood pressure (SBP/DBP) and heart rate (HR);
• Telemetry and 12 lead ECG Analysis [ Time Frame: within 30 min pre-dose, telemetry for 5 min post dose, 12 lead at 30, 90, and 360 min post-dose. ] [ Designated as safety issue: Yes ]

  Telemetry ECG recording of heart rate pre-dose, and during the initial 5 min post-dose.

  A 12-lead ECG (Routine and QT / QTc intervals)at specified intervals

• Blood Values [ Time Frame: at baseline, and at 15, 30, 60, 120, and 360 min post-dose ] [ Designated as safety issue: Yes ]
  Serum glucose and potassium levels;
• Hand Tremor [ Time Frame: at baseline, and at 10, 60, and 360 post-dose ] [ Designated as safety issue: Yes ]
  Hand tremor scores
• General health assessment [ Time Frame: Screening and at or within 7 days after study visit 3 ] [ Designated as safety issue: Yes ]
  Physical examinations
• Laboratory Analysis [ Time Frame: Screening, after each treatment and end of study, within 7 days of study visit 3 ] [ Designated as safety issue: Yes ]
  Lab tests, including CBC, serum comprehensive metabolic panel, and urinalysis for all subjects, and urinary pregnancy test for women of child-bearing potential.

This study examines the pharmacokinetic profile of Armstrong's proposed Epinephrine Inhalation Aerosol USP, an HFA-MDI (E004), in healthy male and female adult volunteers. Safety of E004 will also be evaluated, under augmented dose conditions.

This study is a randomized, evaluator-blind, single dose, three-arm, crossover, PK study, to be conducted in ~18 healthy, male and female, adult volunteers. PK will be studied at two dose strengths (Arm T1 and Arm T2). A currently marketed, non-labeled, Epinephrine CFC-MDI will be used as a Reference Control (Arm C).

• At the Screening Visit and the beginning of each Study Visit, each subject will be trained on the correct self-administration of MDI. The following three randomized treatments will be self-administered, at three Study Visits:

  • Treatment T1: Ten (10) inhalations of the low dose E004(125 mcg/inhalation), totaling 1.25 mg of epinephrine;
  • Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine;
  • Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation, totaling 2.2 mg of epinephrine base equivalent).
• PK blood samples will be taken from a vein at scheduled time points.
• Safety parameters and adverse drug events, if any, will be monitored and documented at each study visit. An End-of-Study (EOS) safety evaluation will be conducted.

• Drug: epinephrine inhalation aerosol
  Single dose 220 mcg/inhalation, 10 inhalations
  Other Name: Primatene Mist
• Drug: epinephrine inhalation aerosol
  HFA propelled epinephrine inhalation aerosol, 125 mcg/inhalation, 10 inhalations
  Other Name: Primatene Mist
• Drug: epinephrine inhalation aerosol
  HFA propelled epinephrine inhalation aerosol, 160 mcg/inhalation, 10 inhalations
  Other Name: Primatene Mist

• Active Comparator: Treatment C
  Active comparator arm utilizing marketed Primatene Mist with CFC propellant at the labeled dose.
  Intervention: Drug: epinephrine inhalation aerosol
• Experimental: Treatment 1
  T1 is HFA propelled epinephrine inhalation aerosol 125 mcg/inhalation
  Intervention: Drug: epinephrine inhalation aerosol
• Experimental: Treatment 2
  HFA propelled epinephrine inhalation aerosol, 160 mcg/inhalation
  Intervention: Drug: epinephrine inhalation aerosol

Inclusion Criteria:

• Generally healthy, male and female adults, 18-30 yrs of age at Screening;
• Having no clinically significant respiratory, cardiovascular and other systemic or organic illnesses, per investigator discretion;
• Women of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control;
• Having properly consented and satisfied all other inclusion/exclusion criteria as required for this protocol.
• Other criteria apply.

Exclusion Criteria:

• A recent or significant smoking history;
• Use of prohibited drugs or failure to observe the drug washout restrictions;
• Having been on other investigational drug/device studies in the last 30 days prior to Screening.
• Other criteria apply