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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
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: epinephrine inhalation aerosol
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase I/II Study Epinephrine Inhalation Aerosol USP, an HFA-MDI Clinical Study-B for Assessment of Pharmacokinetics

Resource links provided by NLM:


Further study details as provided by Amphastar Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 24
Study Start Date: January 2010
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treatment C
Active comparator arm utilizing marketed Primatene Mist with CFC propellant at the labeled dose.
Drug: epinephrine inhalation aerosol
Single dose 220 mcg/inhalation, 10 inhalations
Other Name: Primatene Mist
Experimental: Treatment 1
T1 is HFA propelled epinephrine inhalation aerosol 125 mcg/inhalation
Drug: epinephrine inhalation aerosol
HFA propelled epinephrine inhalation aerosol, 125 mcg/inhalation, 10 inhalations
Other Name: Primatene Mist
Experimental: Treatment 2
HFA propelled epinephrine inhalation aerosol, 160 mcg/inhalation
Drug: epinephrine inhalation aerosol
HFA propelled epinephrine inhalation aerosol, 160 mcg/inhalation, 10 inhalations
Other Name: Primatene Mist

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01143051

Locations
United States, California
Amphastar Location 1
Cypress, California, United States, 90630
Sponsors and Collaborators
Amphastar Pharmaceuticals, Inc.
Investigators
Study Director: Medical Director Amphastar Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01143051     History of Changes
Other Study ID Numbers: API-E004-CL-B
Study First Received: June 7, 2010
Results First Received: February 5, 2014
Last Updated: June 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Amphastar Pharmaceuticals, Inc.:
Asthma
Pharmacokinetics
Epinephrine
Bronchodilator
metered dose inhaler

Additional relevant MeSH terms:
Epinephrine
Epinephryl borate
Racepinephrine
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-Agonists
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Mydriatics
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Sympathomimetics
Therapeutic Uses
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on November 25, 2014