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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01143051
First received: June 7, 2010
Last updated: June 13, 2014
Last verified: June 2014

June 7, 2010
June 13, 2014
January 2010
June 2010   (final data collection date for primary outcome measure)
  • Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine [ Time Frame: 0 to 30 minutes prior to dosing ] [ Designated as safety issue: No ]
    Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at Baseline (prior to dosing) in each treatment period following a specified washout period (3-14 days), and were analyzed using an established analysis method. Baseline concentration (C0) is the concentration of epinephrine measured in the plasma at this time point.
  • Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6]) [ Time Frame: Pre-dose to 6 hours post-dose ] [ Designated as safety issue: No ]
    Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Area under the curve from time zero to 6 hours post-dose (AUC[0-6]) was calculated using the trapezoidal rule.
  • Peak Concentration (Cmax) for Total Epinephrine From Time Zero to 6 Hours Post-dose [ Time Frame: Pre-dose to 6 hours post-dose ] [ Designated as safety issue: No ]
    Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Peak (maximum) concentration (Cmax) is the highest concentration of epinephrine measured in plasma during the treatment period.
  • Time to Reach Peak Concentration (Tmax) for Total Epinephrine [ Time Frame: Pre-dose to 6 hours post-dose ] [ Designated as safety issue: No ]
    Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. tmax is the amount of time it takes for epinephrine to reach peak concentration in plasma during the treatment period.
  • Half-life (t1/2) for Total Epinephrine [ Time Frame: Pre-dose to 6 hours post-dose ] [ Designated as safety issue: No ]
    Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Half-life (t1/2) is the amount of time it takes for epinephrine decrease to half the peak concentration in plasma during the treatment period.
  • Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose [ Time Frame: Pre-dose to 6 hours post-dose ] [ Designated as safety issue: No ]
    Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method.
Pharmacokinetics [ Time Frame: 5, 15, 30, 45, 60 90, 120, 180, 240 and 360 min postdose ] [ Designated as safety issue: No ]
PK blood samples will be taken from a vein in a hand or arm via indwelling anticoagulated IV catheters, or by venipunctures, at scheduled time points
Complete list of historical versions of study NCT01143051 on ClinicalTrials.gov Archive Site
  • Vital Sign Analysis [ 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 to assess general health
  • 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.
  • 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.
Not Provided
Not Provided
 
Pharmacokinetics (PK) Study of Epinephrine Inhalation Aerosol in Healthy Volunteers
Phase I/II Study Epinephrine Inhalation Aerosol USP, an HFA-MDI Clinical Study-B for Assessment of Pharmacokinetics

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.
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Asthma
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
June 2010
June 2010   (final data collection date for primary outcome measure)

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
Both
18 Years to 30 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01143051
API-E004-CL-B
No
Amphastar Pharmaceuticals, Inc.
Amphastar Pharmaceuticals, Inc.
Not Provided
Study Director: Medical Director Amphastar Pharmaceuticals, Inc.
Amphastar Pharmaceuticals, Inc.
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP