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

• ClinicalTrials.gov Identifier: NCT01143051
• Recruitment Status: Completed
• First Posted: June 14, 2010
• Results First Posted: July 15, 2014
• Last Update Posted: September 25, 2018
• Sponsor: Amphastar Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Amphastar Pharmaceuticals, Inc.

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Asthma	Drug: epinephrine inhalation aerosol	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, 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
• Study Start Date: January 2010
• Actual Primary Completion Date: June 2010
• Actual Study Completion Date: June 2010

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine [ Time Frame: 0 to 30 minutes prior to dosing ]
   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.
2. Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6]) [ Time Frame: Pre-dose to 6 hours post-dose ]
   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.
3. Peak Concentration (Cmax) for Total Epinephrine From Time Zero to 6 Hours Post-dose [ Time Frame: Pre-dose to 6 hours post-dose ]
   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.
4. Time to Reach Peak Concentration (Tmax) for Total Epinephrine [ Time Frame: Pre-dose to 6 hours post-dose ]
   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.
5. Half-life (t1/2) for Total Epinephrine [ Time Frame: Pre-dose to 6 hours post-dose ]
   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.
6. Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose [ Time Frame: Pre-dose to 6 hours post-dose ]
   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 :

1. Vital Signs: Systolic Blood Pressure (SBP) [ Time Frame: Pre-dose (baseline) to 360 minutes post-dose ]
   Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
2. Vital Signs: Diastolic Blood Pressure (DBP) [ Time Frame: Pre-dose (baseline) to 360 minutes post-dose ]
   Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
3. Vital Signs: Heart Rate (HR) [ Time Frame: Pre-dose (baseline) to 360 minutes post-dose ]
   Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
4. ECG: QT Interval [ Time Frame: Pre-dose (baseline) to 360 minutes post-dose ]
   Subject QT and QTc Intervals were recorded using a 12-Lead ECG prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
5. ECG: QTc Interval [ Time Frame: Pre-dose (baseline) to 360 minutes post-dose ]
   Subject QT and QTc Intervals were recorded using a 12-Lead ECG prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
6. Serum Glucose Levels [ Time Frame: Pre-dose (baseline) to 360 minutes post-dose ]
   Blood samples used to measure subject serum glucose and potassium levels were collected prior to study drug dosing (baseline) and up to 360 minutes post-dose.
7. Serum Potassium Levels [ Time Frame: Pre-dose (baseline) to 360 minutes post-dose ]
   Blood samples used to measure subject serum glucose and potassium levels were collected prior to study drug dosing (baseline) and up to 360 minutes post-dose.
8. Hand Tremor Scores [ Time Frame: Pre-dose (baseline) to 360 minutes post-dose ]
   Subjects evaluated hand tremor experiences using a scale from 0 to 3 (0: No tremor; 1: Mild, perceivable; 2: Moderate, observable; and 3: Severe, interfering with hand activities). Hand tremors were evaluated prior to study drug dosing (baseline) and up to 360 minutes post-dose.
9. Number of Subjects With Significant Changes in Physical Examination [ Time Frame: Approximately 6 weeks ]
   Physical examinations were performed as a part of Screening and End-of-Study (EOS) procedures. This outcome is a count of the number of subjects that showed a clinically significant change in the EOS physical examination compared to the Screening Visit.
10. Number of Subjects With Significant Changes in Laboratory Tests [ Time Frame: Approximately 6 weeks ]
    Laboratory tests (CBC, serum comprehensive metabolic panel, urinalysis, and urinary pregnancy test for women of childbearing potential) were performed as a part of Screening and End-of-Study (EOS) procedures. This outcome is a count of the number of subjects that showed a clinically significant change in the EOS laboratory tests compared to the Screening Visit.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 30 Years (Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Amphastar Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01143051
• Other Study ID Numbers: API-E004-CL-B
• First Posted: June 14, 2010
• Results First Posted: July 15, 2014
• Last Update Posted: September 25, 2018
• Last Verified: September 2018

Keywords provided by Amphastar Pharmaceuticals, Inc.:

Asthma; Pharmacokinetics; Epinephrine; Bronchodilator; metered dose inhaler

Additional relevant MeSH terms:

Asthma; Respiratory Aspiration; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Respiration Disorders; Pathologic Processes; Epinephrine; Racepinephrine; Epinephryl borate; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Adrenergic beta-Agonists; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Asthmatic Agents; Respiratory System Agents; Mydriatics; Sympathomimetics; Vasoconstrictor Agents