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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06013150




Registration number
NCT06013150
Ethics application status
Date submitted
22/08/2023
Date registered
28/08/2023
Date last updated
28/08/2023

Titles & IDs
Public title
Study of Inhaled DMC-IH1 and Intramuscular (EpiPen®) Epinephrine in Healthy Male and Female Participants.
Scientific 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
Secondary ID [1] 0 0
DMC-CL-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaphylactic Reaction 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Epinephrine
Treatment: Drugs - Placebo

Experimental: Epinephrine - 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)

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


Treatment: Drugs: Epinephrine
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.

Treatment: Drugs: Placebo
Participant in Part 1 of the study will receive matching doses of placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events (AEs)
Timepoint [1] 0 0
Upto 7 days for Part 1; Upto 16 days for Part 2
Primary outcome [2] 0 0
Number of participants with clinical laboratory abnormalities
Timepoint [2] 0 0
Upto 7 days for Part 1; Upto 16 days for Part 2
Primary outcome [3] 0 0
Number of participants with changes in the 12-lead electrocardiogram (ECG)
Timepoint [3] 0 0
Upto 7 days for Part 1; Upto 16 days for Part 2
Primary outcome [4] 0 0
PK Parameters: Assess timepoints of carryover effect of repeated dose of inhaled epinephrine
Timepoint [4] 0 0
Upto 7days post effect in Part 2 of the study
Secondary outcome [1] 0 0
PK Parameters: Time for maximum concentration (Tmax)
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
PK Parameters: Maximum concentration (Cmax)
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
PK Parameters: Area under Curve (AUC)
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
PD parameters: Maximum effect on heart rate and blood pressure (Emax)
Timepoint [4] 0 0
Part 1: 240 minutes postdose;Part 2- 360 mins post dose and carry over effect upto 7 days post dose
Secondary outcome [5] 0 0
PD parameters: Time to maximum effect (TEmax)
Timepoint [5] 0 0
Part 1: 240 minutes postdose;Part 2- 360 mins post dose and carry over effect upto 7 days post dose

Eligibility
Key inclusion criteria
1. 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.

2. Male or female and =18 to =45 years of age at time of signing the ICF.

3. 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.

4. 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).

5. 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).

6. 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).

7. Has no history of anaphylaxis or severe allergy requiring the use of epinephrine.

8. 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]).

9. Has adequate venous access.

10. Is able to demonstrate correct use of the device using a practice device and follow
directions for use.

11. Able to follow contraceptive measures as per Protocol.

12. 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).
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. 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).

2. Participant has a history of significant hypersensitivity or intolerance to lactose
and/or epinephrine.

3. 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.

4. Participant has a positive urine drug screen at Screening and at Baseline (Visit 2/Day
-1).

5. Participant has a positive urine cotinine test at Baseline (Visit 2/Day -1).

6. 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).

7. 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.

8. 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).

9. Participant has a positive alcohol breath test at Screening and prior to randomization
(Day -1/Visit 2).

10. Female participant has a positive serum pregnancy test at Screening and a positive
urine pregnancy test prior to randomization (Day -1/Visit 2).

11. 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.

12. 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.

13. Participant has received any of the following vaccinations:

1. Live vaccine(s) within 1 month prior to Screening or plans to receive such
vaccines during the study.

2. Killed vaccine 1 week prior to randomization (Day -1/Visit 2).

3. COVID-19 vaccine Day -7 through Visit 3 for Part 1 and through Visit 6 for Part 2
(EOS).

14. 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).

15. 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.

16. Participant has any of the following ECG criteria:

1. PR interval >220 ms or <120 ms

2. QRS interval >120 ms

3. QTcF interval >450 ms (males) or >470 ms (females)

4. A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of
a QTc interval >450 ms)

5. ST segment elevation or depression considered to be clinically significant by the
PI or designee

6. T-wave or U-wave abnormalities considered to be clinically significant by the PI
or designee -

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
23/10/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
12/02/2024
Actual
Sample size
Target
63
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
CMAX Clinical Research - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
De Motu Cordis
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06013150
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Peter O'Neil
Address 0 0
peter.oneill@demotucordis.co
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
John Fredatovich
Address 0 0
Country 0 0
Phone 0 0
+61 07 3520 0350
Fax 0 0
Email 0 0
john.fredatovich@demotucordis.co
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06013150