search
Back to results

Study of Inhaled DMC-IH1 and Intramuscular (EpiPen®) Epinephrine in Healthy Male and Female Participants.

Primary Purpose

Anaphylactic Reaction

Status
Not yet recruiting
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
Epinephrine
Placebo
Sponsored by
De Motu Cordis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anaphylactic Reaction

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Is willing to sign an ICF on a voluntary basis and to voluntarily participate in the study, after being able to read the ICF and understand the information contained within, prior to any Screening procedure being undertaken. Male or female and ≥18 to ≤45 years of age at time of signing the ICF. Has a BMI of ≥18.00 to ≤30.00 kg/m2, with a minimum body weight of 45.0 kg and a maximum body weight of 120 kg. Is in good health based on the results of medical and surgical history, physical examination, vital sign measurements, and clinical laboratory evaluations, as assessed by the Investigator (or designee). Has a resting heart rate of ≥45 and ≤90 beats per minute; systolic blood pressure of ≥90 but ≤130 mmHg and diastolic blood pressure of ≥50 but ≤90 mmHg at Screening (Visit 1) and prior to randomisation on Day -1 (Visit 2). Has normal lung function assessed using spirometry and defined by forced vital capacity (FVC) ≥ lower limit of normal (LLN), forced expiratory volume in 1 second/FVC ≥LLN, and peak inspiratory flow rate ≥ LLN at Screening (Visit 1). Has no history of anaphylaxis or severe allergy requiring the use of epinephrine. Is a non-smoker/non-vaping; or social smoker who currently only uses ≤5 cigarettes per month and has used nicotine on ≤5 occasions within 30 days prior to Screening, a negative cotinine test at Visit 2/Day -1, and ability and willingness to refrain from smoking 7 days prior to the first epinephrine dose through the EOS [Part 1: Visit 3; Part 2: Visit 6]). Has adequate venous access. Is able to demonstrate correct use of the device using a practice device and follow directions for use. Able to follow contraceptive measures as per Protocol. Ability and willingness to refrain from undertaking any strenuous exercise (including weightlifting) 48 hours prior to each clinic visit. 14. Ability and willingness to refrain from alcohol and/or drug use from Screening (or at least 1 week prior to dosing) (testing at Day -1 to ensure compliance) until EOS (Part 1:until Visit 3/EOS; Part 2: until Visit 6/EOS). Exclusion Criteria: Participant who is pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time from screening to the end of study visit (Part 1: through Visit 3/EOS; Part 2: through Visit 6/EOS). Participant has a history of significant hypersensitivity or intolerance to lactose and/or epinephrine. Participant has a history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular (including severe pulmonary haemorrhage), gastrointestinal, neurological (including history of migraine requiring specific treatment), respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee) except for fully resolved childhood asthma. Participant has a positive urine drug screen at Screening and at Baseline (Visit 2/Day -1). Participant has a positive urine cotinine test at Baseline (Visit 2/Day -1). Participant took part in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives prior to Baseline (Visit 2/Day -1). Participant used or intends to use any prescription or non-prescription medications/products within 14 days prior to randomization (Day -1) through EOS (Part 1: Visit 3/EOS; Part 2: Visit 6/EOS), with the exception of paracetamol/acetaminophen at the discretion of the Investigator, and contraceptives. Participant has a history of alcoholism or substance or drug abuse-related disorders deemed significant by the Investigator (or designee) (ie, >14 drinks/week for women or >21 drinks/week for men [1 drink=150 mL of wine or 360 mL of beer or 45 mL of hard liquor]) within the last 3 months prior to Screening (Visit 1) and randomization (Day -1/Visit 2). Participant has a positive alcohol breath test at Screening and prior to randomization (Day -1/Visit 2). Female participant has a positive serum pregnancy test at Screening and a positive urine pregnancy test prior to randomization (Day -1/Visit 2). Participant has a positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C virus antibody (anti-HCV) with HCV RNA detected at Screening and hepatitis B core antibody at Screening. Participant has presence of any physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the participant will comply with the protocol or complete the study per protocol. Participant has received any of the following vaccinations: Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study. Killed vaccine 1 week prior to randomization (Day -1/Visit 2). COVID-19 vaccine Day -7 through Visit 3 for Part 1 and through Visit 6 for Part 2 (EOS). Participant had surgery of the nose/paranasal sinuses/mouth/throat within 8 weeks or thoracic surgery within 24 weeks prior to Screening or randomization (Day -1/Visit 2). Participant has any history of clinically relevant respiratory (especially with reduction of respiratory capacity) or history of clinically significant cardiovascular abnormality (eg, including hypertension, ischemic heart disease, previous myocardial infarct, heart failure or conduction abnormalities (SVT, AF, interventricular conduction blocks, etc.) or any other abnormality that in the opinion of the Investigator may pose a safety risk to a participant), or any other abnormality that in the opinion of the Investigator may pose a safety risk to a participant in this study may confound the clinical performance or safety assessment, or may interfere with study participation. Participant has any of the following ECG criteria: PR interval >220 ms or <120 ms QRS interval >120 ms QTcF interval >450 ms (males) or >470 ms (females) A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval >450 ms) ST segment elevation or depression considered to be clinically significant by the PI or designee T-wave or U-wave abnormalities considered to be clinically significant by the PI or designee -

Sites / Locations

  • CMAX Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Epinephrine

Placebo

Arm Description

Dosage Level: Part 1 of the study: Participants across cohort 1 to 3 will receive a single dose of either 1mg or 1.3mg or 1.5mg respectively of epinephrine or placebo via DMC-IHI device. Part 2 of the study: This is an open label where participants will receive multiple doses of inhaled epinephrine via DMC-IHI across 5 cohorts the highest tolerated dose based on safety, PK, PD data from Part 1 of the study on. Dosage form: Single-use capsule based dry powder inhaler or EpiPen® IM Route of administraion: Inhalation (Part 1 and Part 2) and Intramuscular (Part 2)

Drug: Placebo Participants will receive matching placebo across the Part 1 of the study.

Outcomes

Primary Outcome Measures

Number of participants with adverse events (AEs)
Number of participants with clinical laboratory abnormalities
Number of participants with changes in the 12-lead electrocardiogram (ECG)
PK Parameters: Assess timepoints of carryover effect of repeated dose of inhaled epinephrine
Part 1: Pre-dose and multiple timepoints post dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on Days 1, 4, and 9 (Arm 1) and on Days 1, 2, and 9 (Arms 2 and 3).

Secondary Outcome Measures

PK Parameters: Time for maximum concentration (Tmax)
PK Parameters: Maximum concentration (Cmax)
PK Parameters: Area under Curve (AUC)
PD parameters: Maximum effect on heart rate and blood pressure (Emax)
PD parameters: Time to maximum effect (TEmax)

Full Information

First Posted
August 22, 2023
Last Updated
August 22, 2023
Sponsor
De Motu Cordis
Collaborators
Novotech (Australia) Pty Limited
search

1. Study Identification

Unique Protocol Identification Number
NCT06013150
Brief Title
Study of Inhaled DMC-IH1 and Intramuscular (EpiPen®) Epinephrine in Healthy Male and Female Participants.
Official Title
A Phase 1, 2-Part Study in Healthy Male and Female Participants; Part 1 - A Randomised, Double-Blind, Placebo-Controlled, Single Ascending Dose-Escalation Study of Inhaled DMC-IH1; Part 2 - An Open-Label, 3-Arm Study Assessing the Carryover Effects of Inhaled (DMC-IH1) and Intramuscular (EpiPen®) Epinephrine
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 23, 2023 (Anticipated)
Primary Completion Date
January 18, 2024 (Anticipated)
Study Completion Date
February 12, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
De Motu Cordis
Collaborators
Novotech (Australia) Pty Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase 1, randomised, double blind placebo controlled 2-part study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of inhaled DMC-IH1 (epinephrine) and relative bioavailability and carryover effects of Inhaled (DMC-IH1) and Intramuscular(IM) (EpiPen®) Epinephrine in healthy male and female participants.
Detailed Description
DMC-IH1 (Investigational product) inhaler is a proprietary single-use capsule based dry powder inhaler designed for oral pulmonary drug delivery in emergency scenarios. This study is in two parts- Part 1 will enrol 24 participants into 3 cohorts receiving a single ascending dose; Part 2 will enrol 39 participants into 3 arms to receive either DMC-IH1 through the inhaler device or epinephrine IM. Each participant will receive 3 doses of epinephrine either inhaled (DMC-IH1) or IM at differing intervals to assess carryover effect. Both Parts 1 and 2 of the study will comprise 3 periods: Screening, Treatment Period and Follow-up .

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anaphylactic Reaction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
63 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Epinephrine
Arm Type
Experimental
Arm Description
Dosage Level: Part 1 of the study: Participants across cohort 1 to 3 will receive a single dose of either 1mg or 1.3mg or 1.5mg respectively of epinephrine or placebo via DMC-IHI device. Part 2 of the study: This is an open label where participants will receive multiple doses of inhaled epinephrine via DMC-IHI across 5 cohorts the highest tolerated dose based on safety, PK, PD data from Part 1 of the study on. Dosage form: Single-use capsule based dry powder inhaler or EpiPen® IM Route of administraion: Inhalation (Part 1 and Part 2) and Intramuscular (Part 2)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Drug: Placebo Participants will receive matching placebo across the Part 1 of the study.
Intervention Type
Drug
Intervention Name(s)
Epinephrine
Intervention Description
Participants in Part 1 of the study will receive single dose either 1mg, 1.3mg or 1.5mg of an inhaled single dose of Epinephrine or placebo delivered via DMC-IHI device. Participants in the Part 2 of the study will receive multiple doses of the Epinephrine based on MTD of Part 1 of the study.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participant in Part 1 of the study will receive matching doses of placebo
Primary Outcome Measure Information:
Title
Number of participants with adverse events (AEs)
Time Frame
Upto 7 days for Part 1; Upto 16 days for Part 2
Title
Number of participants with clinical laboratory abnormalities
Time Frame
Upto 7 days for Part 1; Upto 16 days for Part 2
Title
Number of participants with changes in the 12-lead electrocardiogram (ECG)
Time Frame
Upto 7 days for Part 1; Upto 16 days for Part 2
Title
PK Parameters: Assess timepoints of carryover effect of repeated dose of inhaled epinephrine
Description
Part 1: Pre-dose and multiple timepoints post dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on Days 1, 4, and 9 (Arm 1) and on Days 1, 2, and 9 (Arms 2 and 3).
Time Frame
Upto 7days post effect in Part 2 of the study
Secondary Outcome Measure Information:
Title
PK Parameters: Time for maximum concentration (Tmax)
Time Frame
Part 1: Pre-dose multiple timepoints post-dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on day 1, 4, 9 (Arm1) and 1,2 and 9 (Arm 2 & 3)
Title
PK Parameters: Maximum concentration (Cmax)
Time Frame
Part 1: Pre-dose multiple timepoints post-dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on day 1, 4, 9 (Arm1) and 1,2 and 9 (Arm 2 & 3)
Title
PK Parameters: Area under Curve (AUC)
Time Frame
Part 1: Pre-dose multiple timepoints post-dose on Day 1; Part 2: Pre-dose and multiple timepoints post-dose on day 1, 4, 9 (Arm1) and 1,2 and 9 (Arm 2 & 3)
Title
PD parameters: Maximum effect on heart rate and blood pressure (Emax)
Time Frame
Part 1: 240 minutes postdose;Part 2- 360 mins post dose and carry over effect upto 7 days post dose
Title
PD parameters: Time to maximum effect (TEmax)
Time Frame
Part 1: 240 minutes postdose;Part 2- 360 mins post dose and carry over effect upto 7 days post dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Is willing to sign an ICF on a voluntary basis and to voluntarily participate in the study, after being able to read the ICF and understand the information contained within, prior to any Screening procedure being undertaken. Male or female and ≥18 to ≤45 years of age at time of signing the ICF. Has a BMI of ≥18.00 to ≤30.00 kg/m2, with a minimum body weight of 45.0 kg and a maximum body weight of 120 kg. Is in good health based on the results of medical and surgical history, physical examination, vital sign measurements, and clinical laboratory evaluations, as assessed by the Investigator (or designee). Has a resting heart rate of ≥45 and ≤90 beats per minute; systolic blood pressure of ≥90 but ≤130 mmHg and diastolic blood pressure of ≥50 but ≤90 mmHg at Screening (Visit 1) and prior to randomisation on Day -1 (Visit 2). Has normal lung function assessed using spirometry and defined by forced vital capacity (FVC) ≥ lower limit of normal (LLN), forced expiratory volume in 1 second/FVC ≥LLN, and peak inspiratory flow rate ≥ LLN at Screening (Visit 1). Has no history of anaphylaxis or severe allergy requiring the use of epinephrine. Is a non-smoker/non-vaping; or social smoker who currently only uses ≤5 cigarettes per month and has used nicotine on ≤5 occasions within 30 days prior to Screening, a negative cotinine test at Visit 2/Day -1, and ability and willingness to refrain from smoking 7 days prior to the first epinephrine dose through the EOS [Part 1: Visit 3; Part 2: Visit 6]). Has adequate venous access. Is able to demonstrate correct use of the device using a practice device and follow directions for use. Able to follow contraceptive measures as per Protocol. Ability and willingness to refrain from undertaking any strenuous exercise (including weightlifting) 48 hours prior to each clinic visit. 14. Ability and willingness to refrain from alcohol and/or drug use from Screening (or at least 1 week prior to dosing) (testing at Day -1 to ensure compliance) until EOS (Part 1:until Visit 3/EOS; Part 2: until Visit 6/EOS). Exclusion Criteria: Participant who is pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time from screening to the end of study visit (Part 1: through Visit 3/EOS; Part 2: through Visit 6/EOS). Participant has a history of significant hypersensitivity or intolerance to lactose and/or epinephrine. Participant has a history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular (including severe pulmonary haemorrhage), gastrointestinal, neurological (including history of migraine requiring specific treatment), respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee) except for fully resolved childhood asthma. Participant has a positive urine drug screen at Screening and at Baseline (Visit 2/Day -1). Participant has a positive urine cotinine test at Baseline (Visit 2/Day -1). Participant took part in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives prior to Baseline (Visit 2/Day -1). Participant used or intends to use any prescription or non-prescription medications/products within 14 days prior to randomization (Day -1) through EOS (Part 1: Visit 3/EOS; Part 2: Visit 6/EOS), with the exception of paracetamol/acetaminophen at the discretion of the Investigator, and contraceptives. Participant has a history of alcoholism or substance or drug abuse-related disorders deemed significant by the Investigator (or designee) (ie, >14 drinks/week for women or >21 drinks/week for men [1 drink=150 mL of wine or 360 mL of beer or 45 mL of hard liquor]) within the last 3 months prior to Screening (Visit 1) and randomization (Day -1/Visit 2). Participant has a positive alcohol breath test at Screening and prior to randomization (Day -1/Visit 2). Female participant has a positive serum pregnancy test at Screening and a positive urine pregnancy test prior to randomization (Day -1/Visit 2). Participant has a positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C virus antibody (anti-HCV) with HCV RNA detected at Screening and hepatitis B core antibody at Screening. Participant has presence of any physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the participant will comply with the protocol or complete the study per protocol. Participant has received any of the following vaccinations: Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study. Killed vaccine 1 week prior to randomization (Day -1/Visit 2). COVID-19 vaccine Day -7 through Visit 3 for Part 1 and through Visit 6 for Part 2 (EOS). Participant had surgery of the nose/paranasal sinuses/mouth/throat within 8 weeks or thoracic surgery within 24 weeks prior to Screening or randomization (Day -1/Visit 2). Participant has any history of clinically relevant respiratory (especially with reduction of respiratory capacity) or history of clinically significant cardiovascular abnormality (eg, including hypertension, ischemic heart disease, previous myocardial infarct, heart failure or conduction abnormalities (SVT, AF, interventricular conduction blocks, etc.) or any other abnormality that in the opinion of the Investigator may pose a safety risk to a participant), or any other abnormality that in the opinion of the Investigator may pose a safety risk to a participant in this study may confound the clinical performance or safety assessment, or may interfere with study participation. Participant has any of the following ECG criteria: PR interval >220 ms or <120 ms QRS interval >120 ms QTcF interval >450 ms (males) or >470 ms (females) A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval >450 ms) ST segment elevation or depression considered to be clinically significant by the PI or designee T-wave or U-wave abnormalities considered to be clinically significant by the PI or designee -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Fredatovich
Phone
+61 07 3520 0350
Email
john.fredatovich@demotucordis.co
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter O'Neil
Organizational Affiliation
peter.oneill@demotucordis.co
Official's Role
Study Director
Facility Information:
Facility Name
CMAX Clinical Research
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
CMAX C Research
First Name & Middle Initial & Last Name & Degree
Angela Rowland, Dr
Email
Teamrowland08@yahoo.com.au

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of Inhaled DMC-IH1 and Intramuscular (EpiPen®) Epinephrine in Healthy Male and Female Participants.

We'll reach out to this number within 24 hrs