Study to Explore the Pharmacokinetics and Pharmacodynamics of Epinephrine in Healthy Male and Female Subjects With Different Skin to Muscle Depth (STMD)

An Single-dose, Open Label, Randomized Cross-over Study to Explore the Pharmacokinetics and Pharmacodynamics of Epinephrine in Healthy Male and Female Subjects With Different Skin to Muscle Depth (STMD)

A single dose, open label, randomized cross-over study to explore the pharmacokinetics and pharmacodynamics of epinephrine in healthy male and female subjects

Study Overview

• Status: Completed
• Conditions: Anaphylaxis
• Intervention / Treatment: Device: Part 1; Device: Part 2 Group 1; Drug: Part 2 group 2; Device: Part 2 group 3; Device: Part 2 Group 4

Detailed Description

A single dose, open label, randomized cross-over study to explore the pharmacokinetics and pharmacodynamics of epinephrine in healthy male and female subjects with different skin-to-muscle depth (STMD) of the thigh after injections with four different marketed auto-injectors

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Wegenerstrasse 13
    • Neu-Ulm, Wegenerstrasse 13, Germany, 89231
      • Nuvisan GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 54 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male and female subjects, between 18 and 54 years of age (inclusive).
2. Subjects who are able and willing to give written informed consent.
3. Body mass index (BMI) between 28.0 and 40.0 kg/m² (inclusive). Weight on Day -1 may not have changed by more than 3 kg compared to screening.
4. Compressed STMD of 10 mm and above (Part 1+2).
5. Non-smoker for at least 6 months.

Exclusion Criteria:

1. Receipt of medication (prescription or non-prescription) within 14 days prior to the planned drug administration, except for occasional use of paracetamol or ibuprofen.
2. Receipt of any of the following medications within the previous 6 months; beta adrenergic blockers, tricyclic antidepressants, monoamine oxidase inhibitors and catechol-O-methyl transferase inhibitors, methylphenidate, amphetamines, any drugs that may sensitize the heart to arrhythmias, including digitalis and quinidine.

3. History or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neuropsychological, endocrine, gastrointestinal or pulmonary diseases especially asthma bronchiale. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which could affect the endpoint analysis if the disease/condition exacerbated during the study.

   History or presence of silent infections, including positive tests for HIV1, HIV2, Hepatitis B or C.

4. Presence of any disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
5. Hypersensitivity to epinephrine or any of the excipients (e.g. metabisulphite).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Group 1; A single dose of 500 μg epinephrine (0.5 mL Suprarenin®) will be administered i.m. and s.c. by using a needle and a syringe in randomized order.	Device: Part 1; A single dose of 500 μg epinephrine (0.5 mL Suprarenin®) will be administered i.m. and s.c. by using a needle and a syringe in randomized order; Other Names: Group 1
Experimental: Part 2 group 1; 300 μg epinephrine auto-injector (Emerade, Bausch and Lomb, 23 mm needle length)	Device: Part 2 Group 1; 300 μg epinephrine auto-injector (Emerade, Bausch and Lomb, 23 mm needle length); Other Names: Group 1
Experimental: Part 2 Group 2; 500 μg epinephrine auto-injector (Emerade, Bausch and Lomb, 23 mm needle length)	Drug: Part 2 group 2; 500 μg epinephrine auto-injector (Emerade, Bausch and Lomb, 23 mm needle length); Other Names: Group 2
Experimental: Part 2 Group 3; 300 μg epinephrine auto-injector (Fastjekt, MEDA Pharma, 16 mm needle length)	Device: Part 2 group 3; 300 μg epinephrine auto-injector (Fastjekt, MEDA Pharma, 16 mm needle length); Other Names: Group 3
Experimental: Part 2 Group 4; 300 μg epinephrine auto-injector (Jext, Alk-Abelló, 15 mm needle length)	Device: Part 2 Group 4; 300 μg epinephrine auto-injector (Jext, Alk-Abelló, 15 mm needle length); Other Names: Group 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum observed drug concentration	14 days
tmax	Time of the maximum drug concentration (obtained without interpolation). If the maximum value occurs at more than one time point, tmax is defined as the first time point with this value.	14 days

Collaborators and Investigators

• Sponsor: Bausch & Lomb Incorporated
• Investigators: Principal Investigator: Beate Klaus, MD, Baush and Lomb

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2017
• Primary Completion (Actual): September 28, 2018
• Study Completion (Actual): October 15, 2018

Study Registration Dates

• First Submitted: July 21, 2017
• First Submitted That Met QC Criteria: September 13, 2017
• First Posted (Actual): September 14, 2017

Study Record Updates

• Last Update Posted (Actual): June 21, 2019
• Last Update Submitted That Met QC Criteria: June 20, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Anaphylaxis
• Other Study ID Numbers: N-A-PH1-15-050

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No