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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02868996




Registration number
NCT02868996
Ethics application status
Date submitted
8/08/2016
Date registered
16/08/2016
Date last updated
7/12/2017

Titles & IDs
Public title
An Open Label, Phase 1b, Ascending Dose Study of DM199
Scientific title
An Open Label, Phase 1b, Single CENTER, Ascending Dose Study TO ASSESS THE SAFETY AND TOLERABILITY of DM199 With a Comparative Pharmacokinetic Study of DM199 Administered Intravenously and a Bioavailability Assessment of Subcutaneous Administration of DM199 in Normal Healthy Subjects
Secondary ID [1] 0 0
DM199-2016-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Recombinant human tissue kallikrein

Experimental: Low dose (Part A) - Recombinant human tissue kallikrein

Experimental: Medium low dose (Part A) - Recombinant human tissue kallikrein

Experimental: Medium high dose (Part A) - Recombinant human tissue kallikrein

Experimental: High dose (Part A) - Recombinant human tissue kallikrein

Experimental: Subcutaneous (Part B) - Recombinant human tissue kallikrein

Experimental: IV (Part B) - Recombinant human tissue kallikrein


Treatment: Drugs: Recombinant human tissue kallikrein
Intravenous DM199

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 - Assessment of safety of intravenous dosing
Timepoint [1] 0 0
30 days
Secondary outcome [1] 0 0
Concentration of DM199 in plasma - Assess plasma drug levels
Timepoint [1] 0 0
3 days
Secondary outcome [2] 0 0
Concentration of bradykinin in plasma - Assess drug associated biomarkers (e.g. plasma bradykinin levels)
Timepoint [2] 0 0
3 days

Eligibility
Key inclusion criteria
1. Male or female between 18 and 50 years of age (inclusive);

2. Healthy with no clinically significant medical problems;

3. BMI between 18 to 30 kg/m2 with a weight between 50 to 100 kg (both inclusive);

4. No history of alcohol or drug abuse (Paracetamol, Barbiturates, Benzodiazepines,
Cocaine, Methadone, Amphetamines, Methamphetamines, Opiates, Phencyclidine,
Tetrahydrocannabinol (cannabis), Tricyclic Antidepressants). Subjects should be
enrolled only after passing the urine drug screen (positive test for paracetamol will
be allowed);

5. Non-smokers or light smokers (Less than 5 cigarettes per day) by history and planned
during the study;

6. No history of significant allergic diathesis such as urticaria, angioedema or
anaphylaxis;

7. Receiving no chronic medications that affect blood pressure control, the bradykinin or
angiotensin system including angiotensin-converting-enzyme inhibitors (ACEi) or
angiotensin receptor blockers (ARB);

8. Willing and able to sign written, informed consent.
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any significant past or current cardiac, pulmonary, hepatic, renal or other medical
condition which in the opinion of the investigator would make participation of the
subject in this study medically unsafe or compromise the accuracy of assessment of
safety, pharmacokinetic and pharmacodynamic data of the study;

2. Subjects who have abnormal safety labs outside the local lab ranges will be excluded
at PI's discretion based on his/her assessment of clinical significance (can be
repeated once at screening at PI's discretion);

3. Subjects with past medical history of malignancy except basal cell or squamous cell
carcinoma of the skin who have had curative surgical treatment and at least 6 months
have elapsed since the procedure;

4. A value outside the specified range of 90 mm Hg - 140 mm Hg for systolic blood
pressure and 50 mm Hg - 90 mm Hg for diastolic blood pressure (both inclusive) at
screening (can be repeated once at screening as per PI's discretion);

5. Subjects using angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor
blockers (ARB) to control blood pressure;

6. History of clinically significant acute bacterial, viral, or fungal systemic
infections in the last 4 weeks prior to screening;

7. Clinical or laboratory evidence of an active infection at the time of screening;

8. Known alpha 1-antitrypsin deficiency (a1-antitrypsin deficiency);

9. Serological evidence of human immunodeficiency virus (HIV), hepatitis B surface
antigen (HBsAg), or anti-hepatitis C virus (Anti-HCV) at screening;

10. Vaccination within 3 months of screening for the study or requiring vaccination during
the study or within 3 months after completion of the study;

11. Females who are pregnant or nursing;

12. Females of childbearing potential (i.e., any woman who is not surgically sterile e.g.,
hysterectomy, bilateral oophorectomy or >1-year postmenopause status confirmed by
follicle-stimulating hormone (FSH) levels as defined by established lab ranges) and
all men who, if participating in heterosexual sexual activity that could lead to
pregnancy are unable or unwilling to practice medically effective contraception during
the study. They should agree to use two reliable methods of contraception (e.g.,
double-barrier condom plus diaphragm, condom or diaphragm plus a stable dose of
hormonal contraception) throughout the study period and until 3 months after receiving
study drug. Women of childbearing potential will require compulsory pregnancy testing.
A negative pregnancy test (serum and urine) will be documented during screening and at
Day -1 respectively;

13. Participation in any other drug study within 8 weeks or 5 half-lives of the study
drug, whichever is longer;

14. Unable or unwilling to comply with the protocol requirements for study visits and
procedures;

15. Subjects who do not have good venous access for infusion of study drug or for blood
sampling;

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Linear Clinical Research - Perth
Recruitment postcode(s) [1] 0 0
- Perth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
DiaMedica Therapeutics Inc
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 1B study to assess the safety, tolerability and pharmacokinetics of DM199 in
healthy volunteers. The study will be consist of two parts: Part A will focus on intravenous
dosing and Part B will directly compare intravenous dosing with subcutaneous dosing.
Trial website
https://clinicaltrials.gov/show/NCT02868996
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications