An Open Label, Phase 1b, Ascending Dose Study of DM199

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

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.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: Recombinant human tissue kallikrein

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia
      • Linear Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

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 (α1-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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Low dose (Part A); Recombinant human tissue kallikrein	Drug: Recombinant human tissue kallikrein; Intravenous DM199; Other Names: DM199
EXPERIMENTAL: Medium low dose (Part A); Recombinant human tissue kallikrein	Drug: Recombinant human tissue kallikrein; Intravenous DM199; Other Names: DM199
EXPERIMENTAL: Medium high dose (Part A); Recombinant human tissue kallikrein	Drug: Recombinant human tissue kallikrein; Intravenous DM199; Other Names: DM199
EXPERIMENTAL: High dose (Part A); Recombinant human tissue kallikrein	Drug: Recombinant human tissue kallikrein; Intravenous DM199; Other Names: DM199
EXPERIMENTAL: Subcutaneous (Part B); Recombinant human tissue kallikrein	Drug: Recombinant human tissue kallikrein; Intravenous DM199; Other Names: DM199
EXPERIMENTAL: IV (Part B); Recombinant human tissue kallikrein	Drug: Recombinant human tissue kallikrein; Intravenous DM199; Other Names: DM199

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Assessment of safety of intravenous dosing	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of DM199 in plasma	Assess plasma drug levels	3 days
Concentration of bradykinin in plasma	Assess drug associated biomarkers (e.g. plasma bradykinin levels)	3 days

Collaborators and Investigators

• Sponsor: DiaMedica Therapeutics Inc
• Collaborators: Novotech (Australia) Pty Limited

Publications and helpful links

Helpful Links

• Safety, tolerability and pharmacokinetic profile of recombinant human tissue kallikrein, DM199, after intravenous and subcutaneous administration in healthy volunteers

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (ACTUAL): March 1, 2017
• Study Completion (ACTUAL): March 1, 2017

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: August 11, 2016
• First Posted (ESTIMATE): August 16, 2016

Study Record Updates

• Last Update Posted (ACTUAL): December 7, 2017
• Last Update Submitted That Met QC Criteria: December 5, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Coagulants; Reproductive Control Agents; Fertility Agents; Fertility Agents, Male; Kallikreins
• Other Study ID Numbers: DM199-2016-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES