Adult healthy participants (Part A) and adults recently taking ACE inhibitors (Part B) Not Applicable
Conditions
Interventions
Part A: DM199 will be given as a single intravenous dose diluted into 50 ml of normal saline in a PVC bag and controlled IV kit materials. A minimum of three participant cohorts will be dosed. The fir
Sponsors
DiaMedica Therapuetics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. =18 years of age 2. Part A only: healthy participants with no clinically significant medical problems and taking no medications for a chronic medical condition (oral supplements and vitamins as well as oral contraception medications are allowed) 3. Part B only: non-healthy participants recently taking ACE inhibitor medications: 3.1. Non-healthy participants taking ACE inhibitor medications for chronic medical conditions including hypertension, diabetes, or mild congestive heart failure with the last dose of medication taken >24 hours prior to the start of the IV infusion 3.2. Participant is willing to forego taking prescribed ACE inhibitor medication through the duration of the study or at minimum do not restart ACE inhibitor until 24 hours after completion of the IV infusion (i.e., half-life of DM199 given IV is approximately 4 hours and 24 hours is greater than 5 half-lives) 3.3. All other chronic medications may be allowed if taking stable doses for at least 3 months with no new recent medications, and with pre-approval from the Sponsor Medical Monitor 4. Weight between 50 and 130 kg 5. No history of alcohol or drug abuse (barbiturates, benzodiazepines, cocaine, methadone, amphetamines, methamphetamines, opiates, tetrahydrocannabinol [cannabis]) 6. Non-smokers or light smokers (<5 cigarettes per day or approximately equivalent nicotine amount) by history and planned during the study; smoking includes tobacco and nicotine only vaping 7. No history of significant allergic diathesis such as urticaria, angioedema or anaphylaxis 8. Willing and able to sign written, informed consent 9. Participant is willing and able to comply with the study protocol, in the PI's opinion
Exclusion criteria
Exclusion criteria: 1. Participant has a positive drug test and/or a positive alcohol breath test 2. Any significant past or current cardiac, pulmonary, hepatic, renal or other medical condition which in the opinion of the investigator would make the participation of the participant in this study medically unsafe or compromise the accuracy of assessment of safety, and PK data of the study 3. Participants who have abnormal safety labs outside the local lab ranges will be excluded at the PI’s discretion based on his/her assessment of clinical significance (can be repeated once at Screening at the PI’s discretion) 4. Participants with a past medical history of malignancy except for 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 5. A value below the specified range of 100 mmHg for SBP OR 60 mmHg for DBP at Screening (can be repeated once at Screening as per PI’s discretion) 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 HIV, HBsAg, or anti-HCV at Screening 10. Females who are pregnant or nursing 11. Females of childbearing potential (i.e., any woman who is not surgically sterile e.g., hysterectomy, bilateral oophorectomy or >1-year postmenopausal status confirmed by 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 (eg, double-barrier condom plus diaphragm, condom or diaphragm plus a stable dose of hormonal contraception) throughout the study period and until 1 month after receiving the study drug. Women of childbearing potential (WOCBP) will require compulsory pregnancy testing. A negative pregnancy test (urine) will be documented during Screening and on Day -1 respectively 12. Participation in any other drug study within 8 weeks or 5 half-lives of the study drug, whichever is longer 13. Unable or unwilling to comply with the protocol requirements for study visits and procedures 14. Participants who do not have good venous access for infusion of study drug or for blood sampling
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The safety of a single dose of DM199 administered by IV in a PVC bag will be assessed as follows: 1. Safety is measured by the incidence, frequency, severity, and causality of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) evaluated continuously while in the Phase 1 unit from Screening to Day 3 2. Tolerability of DM199 is measured by the incidence and severity of infusion-related reactions during the infusion on Day 1 and after the infusion up to Day 3 3. Safety is measured by change in physical examination (PE) findings from the initial baseline physical exam on day minus 1, to a PE at 24 hours post-infusion start, to a PE at 48 hours post-infusion start 4. Safety is measured by change in vital sign measurements (resting heart rate, systolic blood pressure [SBP], diastolic blood pressure [DBP], respiratory rate, and body temperature) from the initial baseline vital signs on day one (pre-dose), and blood pressure and heart rate at 5, 10,15, 20, 30, 40, 50,60, 90 minutes post the start of the study drug infusion, and also at 2, 3, 4, 8, 12 hours, and full vital signs again at 24 and 48 hours post-infusion start 5. Safety is measured by change in hematology and chemistry parameters from baseline (day 1 pre-dose) and 24 hours post-dose 6. Safety is measured by change in 12-lead electrocardiogram (ECG) from baseline, at infusion end (approximately 60 minutes post-dose on Day 1), and 24 hours post-dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 05/06/2023: 1. Pharmacokinetics of DM199 will be measured by the plasma concentrations of DM199/KLK1 at baseline (day 1 pre-dose), and at 5, 10 ,15, 20, 30, 40, 50, 60, 90 minutes post the start of the study drug infusion, and also at 2, 3, 4, 8, and 12, 24 and 48 hours post infusion start for Part A participants. For Part B participants, pharmacokinetics of DM199 will be measured by the plasma concentrations of DM199/KLK1 at screening, baseline (day 1 pre-dose), and at 5, 15, 30, 50, 90 minutes post the start of the study drug infusion, and also at 4, 12, 24 and 48 hours post infusion start. 2. Immunogenicity of DM199 will be measured by the plasma DM199 antidrug antibodies (ADA) at baseline (day 1 pre-dose), and at 48 hours post infusion start for all participants. _____ Previous secondary outcome measures: 1. Pharmacokinetics of DM199 will be measured by the plasma concentrations of DM199/KLK1 at baseline (day 1 pre-dose), and at 5, 10 ,15, 20, 30, 40, 50, 60, 90 minutes post the start of the study drug infusion, and also at 2, 3, 4, 8, and 12, 24 and 48 hours post infusion start 2. Immunogenicity of DM199 will be measured by the plasma DM199 antidrug antibodies (ADA) at baseline (day 1 pre-dose), and at 48 hours post infusion start | — |
Countries
Australia
Contacts
Public ContactJulie Daves
Outcome results
None listed