NCT01737892

Brief Summary

This study examines the pharmacokinetic profile of Armstrong's proposed Epinephrine Inhalation Aerosol USP, an HFA-MDI (E004), using a stable isotope deuterium-labeled epinephrine (epinephrine-d3) to differentiate the administered drug from the endogenous epinephrine, in healthy male and female adult volunteers. The current study is designed to complement an earlier PK study, API-E004-CL-B, for a more thorough evaluation of the E004 PK. Safety of E004 will also be evaluated.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at P25-P50 for phase_1 asthma

Timeline
Completed

Started Nov 2012

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2012

Completed
Same day until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2012

Completed
19 days until next milestone

First Submitted

Initial submission to the registry

November 20, 2012

Completed
10 days until next milestone

First Posted

Study publicly available on registry

November 30, 2012

Completed
Last Updated

March 17, 2016

Status Verified

February 1, 2016

Enrollment Period

Same day

First QC Date

November 20, 2012

Last Update Submit

February 18, 2016

Conditions

Asthma

Keywords

AsthmaPharmacokineticsEpinephrineBronchodilatorMetered dose inhaler

Outcome Measures

Primary Outcomes (1)

  • Calculation and Comparison of relative Bioavailability of Epinephrine

    Blood PK samples will be collected at each visit for both study arms, then the Area Under the Curve (s) will be calculated for both arms and compared to give relative bioavailability

    up to 30 min predose and at 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 minutes postdose

Secondary Outcomes (4)

  • Vital Signs

    up to 30 min predose and at 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 minutes postdose

  • 12-lead ECG (Routine and QT/QTc analysis)

    up to 30 min predose and at 5, 10, 15, 20, 30, 60, 120, and 360 minutes postdose

  • Physical Examinations

    up to 30 min predose and after 360 min post last dose

  • Lab tests

    up to 30 min predose

Study Arms (2)

Arm T-Epinephrine Inhalation Aerosol HFA

EXPERIMENTAL

Experimental arm utilizing Epinephrine HFA-MDI (E004)

Drug: Arm T Epinephrine Inhalation Aerosol HFA, 125 mcg, 1 inhalation

Arm C-Epinephrine Inhalation Aerosol CFC

ACTIVE COMPARATOR

Active comparator arm utilizing Epinephrine CFC-MDI

Drug: Arm C-Epinephrine Inhalation Aerosol CFC

Interventions

Arm T Epinephrine Inhalation Aerosol HFA, 125 mcg, 1 inhalationDRUG

Epinephrine Inhalation Aerosol HFA, Single dose 125 mcg, 1 inhalation

Arm T-Epinephrine Inhalation Aerosol HFA
Arm C-Epinephrine Inhalation Aerosol CFCDRUG

Epinephrine Inhalation Aerosol - CFC, Single dose 220 mcg, 1 inhalation

Also known as: Primatene Mist
Arm C-Epinephrine Inhalation Aerosol CFC

Eligibility Criteria

Age18 Years - 30 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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;
  • Body weight greater than or equal to 50 kg for men and greater than or equal to 45 kg for women, and BMI within the range of 18.5 - 30.0 kg/m2 inclusive
  • Sitting blood pressure less than or equal to 135/90 mmHg;
  • Demonstrating negative alcohol/drug screen tests;
  • Demonstrating negative HIV, HBsAg and HCV-Ab screen tests;
  • Women of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control;

You may not qualify if:

  • A smoking history of more than or equal to 10 pack-years, or having smoked within 6 months prior to Screening;
  • Upper respiratory tract infections within 2 weeks, or lower respiratory tract infection within 4 weeks, prior to Screening
  • Any current or recent respiratory conditions that, per investigator discretion, might significantly affect pharmacodynamic response to the study drugs, including but not limited to: asthma, COPD, cystic fibrosis, bronchiectasis, tuberculosis, emphysema, etc.
  • Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine (including diabetes), psychiatric, neoplastic or other illnesses that in the opinion of the investigator could impact on the conduct, safety and evaluation of the study
  • Known intolerance or hypersensitivity to any of the study MDI ingredients (i.e., epinephrine, HFA-134a, CFC-12, CFC-114, polysorbate-80, ethanol, thymol, nitric acid and ascorbic acid)
  • Use of prohibited drugs or failure to observe the drug washout restrictions
  • Having been on other investigational drug/device studies, or donated blood, in the last 30 days prior to Screening.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

West Coast Clinical Trials, LLC

Cypress, California, 90630, United States

Location

Related Publications (6)

  • Pinnas JL, Schachtel BP, Chen TM, Roseberry HR, Thoden WR. Inhaled epinephrine and oral theophylline-ephedrine in the treatment of asthma. J Clin Pharmacol. 1991 Mar;31(3):243-7. doi: 10.1002/j.1552-4604.1991.tb04969.x.

    PMID: 2019665BACKGROUND

  • Hendeles L, Marshik PL, Ahrens R, Kifle Y, Shuster J. Response to nonprescription epinephrine inhaler during nocturnal asthma. Ann Allergy Asthma Immunol. 2005 Dec;95(6):530-4. doi: 10.1016/S1081-1206(10)61014-9.

    PMID: 16400891BACKGROUND

  • Warren JB, Doble N, Dalton N, Ewan PW. Systemic absorption of inhaled epinephrine. Clin Pharmacol Ther. 1986 Dec;40(6):673-8. doi: 10.1038/clpt.1986.243.

    PMID: 3780129BACKGROUND

  • Cripps A, Riebe M, Schulze M, Woodhouse R. Pharmaceutical transition to non-CFC pressurized metered dose inhalers. Respir Med. 2000 Jun;94 Suppl B:S3-9.

    PMID: 10919679BACKGROUND

  • Dickinson BD, Altman RD, Deitchman SD, Champion HC. Safety of over-the-counter inhalers for asthma: report of the council on scientific affairs. Chest. 2000 Aug;118(2):522-6. doi: 10.1378/chest.118.2.522.

    PMID: 10936150BACKGROUND

  • Kushner DJ, Baker A, Dunstall TG. Pharmacological uses and perspectives of heavy water and deuterated compounds. Can J Physiol Pharmacol. 1999 Feb;77(2):79-88.

    PMID: 10535697BACKGROUND

MeSH Terms

Conditions

Asthma

Interventions

Epinephrine

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System Diseases

Intervention Hierarchy (Ancestors)

EthanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsAminesBiogenic MonoaminesBiogenic AminesCatecholaminesCatecholsPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbons

Study Officials

  • Vladimir Evilevitch, M.D.

    Amphastar Pharmaceuticals, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 20, 2012

First Posted

November 30, 2012

Study Start

November 1, 2012

Primary Completion

November 1, 2012

Study Completion

November 1, 2012

Last Updated

March 17, 2016

Record last verified: 2016-02

Locations

US(1)