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
Results First Received: February 5, 2014  
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
Condition: Asthma
Intervention: Drug: epinephrine inhalation aerosol

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited from a specialty clinic in Cypress, CA between 04/29/2010 and 05/27/2010

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 38 subjects were screened, 24 subjects passed screening, consented and were randomized for participation in the study. The IRB approval date was 04/29/2010, the last subject was screened on 05/27/2010.

Reporting Groups
  Description
C, T1, T2 Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 2: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 3: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min.
C, T2, T1 Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 2: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 3: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min.
T1, C, T2 Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 2: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 3: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min.
T1, T2, C Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 2: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 3: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min.
T2, C, T1 Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 2: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 3: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min.
T2, T1, C Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 2: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 3 Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min.

Participant Flow for 5 periods

Period 1:   Visit 1
    C, T1, T2     C, T2, T1     T1, C, T2     T1, T2, C     T2, C, T1     T2, T1, C  
STARTED     4     4     4     4     4     4  
COMPLETED     4     4     4     4     4     4  
NOT COMPLETED     0     0     0     0     0     0  

Period 2:   3-14 Day Washout
    C, T1, T2     C, T2, T1     T1, C, T2     T1, T2, C     T2, C, T1     T2, T1, C  
STARTED     4     4     4     4     4     4  
COMPLETED     4     4     3     4     4     4  
NOT COMPLETED     0     0     1     0     0     0  
Withdrawal by Subject                 0                 0                 1                 0                 0                 0  

Period 3:   Visit 2
    C, T1, T2     C, T2, T1     T1, C, T2     T1, T2, C     T2, C, T1     T2, T1, C  
STARTED     4     4     3     4     4     4  
COMPLETED     4     4     3     4     4     4  
NOT COMPLETED     0     0     0     0     0     0  

Period 4:   3-14 Day Washout
    C, T1, T2     C, T2, T1     T1, C, T2     T1, T2, C     T2, C, T1     T2, T1, C  
STARTED     4     4     3     4     4     4  
COMPLETED     4     4     3     4     4     3  
NOT COMPLETED     0     0     0     0     0     1  
Withdrawal by Subject                 0                 0                 0                 0                 0                 1  

Period 5:   Visit 3
    C, T1, T2     C, T2, T1     T1, C, T2     T1, T2, C     T2, C, T1     T2, T1, C  
STARTED     4     4     3     4     4     3  
COMPLETED     4     4     3     4     4     3  
NOT COMPLETED     0     0     0     0     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
C, T1, T2 Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 2: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 3: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min.
C, T2, T1 Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 2: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 3: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min.
T1, C, T2 Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 2: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 3: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min.
T1, T2, C Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 2: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 3: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min.
T2, C, T1 Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 2: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 3: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min.
T2, T1, C Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 2: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 3 Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min.
Total Total of all reporting groups

Baseline Measures
    C, T1, T2     C, T2, T1     T1, C, T2     T1, T2, C     T2, C, T1     T2, T1, C     Total  
Number of Participants  
[units: participants]
  4     4     4     4     4     4     24  
Age  
[units: participants]
             
<=18 years     0     0     0     0     0     0     0  
Between 18 and 65 years     4     4     4     4     4     4     24  
>=65 years     0     0     0     0     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  24.0  ± 2.94     25.3  ± 4.27     24.0  ± 3.37     21.8  ± 1.71     25.3  ± 0.50     22.0  ± 3.56     23.7  ± 3.01  
Gender  
[units: participants]
             
Female     1     2     1     2     1     2     9  
Male     3     2     3     2     3     2     15  
Region of Enrollment  
[units: participants]
             
United States     4     4     4     4     4     4     24  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine   [ Time Frame: 0 to 30 minutes prior to dosing ]

2.  Primary:   Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6])   [ Time Frame: Pre-dose to 6 hours post-dose ]

3.  Primary:   Peak Concentration (Cmax) for Total Epinephrine From Time Zero to 6 Hours Post-dose   [ Time Frame: Pre-dose to 6 hours post-dose ]

4.  Primary:   Time to Reach Peak Concentration (Tmax) for Total Epinephrine   [ Time Frame: Pre-dose to 6 hours post-dose ]

5.  Primary:   Half-life (t1/2) for Total Epinephrine   [ Time Frame: Pre-dose to 6 hours post-dose ]

6.  Primary:   Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose   [ Time Frame: Pre-dose to 6 hours post-dose ]

7.  Secondary:   Vital Sign Analysis   [ Time Frame: at baseline, and at 10, 30, 60, 120, 180, and 360 min post-dose. ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes

8.  Secondary:   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. ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes

9.  Secondary:   Blood Values   [ Time Frame: at baseline, and at 15, 30, 60, 120, and 360 min post-dose ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes

10.  Secondary:   Hand Tremor   [ Time Frame: at baseline, and at 10, 60, and 360 post-dose ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes

11.  Secondary:   General Health Assessment   [ Time Frame: Screening and at or within 7 days after study visit 3 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes

12.  Secondary:   Laboratory Analysis   [ Time Frame: Screening, after each treatment and end of study, within 7 days of study visit 3 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Stephen A. Campbell, Esq.
Organization: Amphastar Pharmaceuticals, Inc.
phone: (909) 980-9484 ext 2016
e-mail: stephenc@amphastar.com


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