A Double-Blind, Placebo-Controlled, Dose-Escalation Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 721744, an Antisense Oligonucleotide Inhibitor of PKK, Administered Subcutaneously to Healthy Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Peak plasma Concentration (Cmax) of Donidalorsen
Study Overview
Brief Summary
The purpose is to assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Donidalorsen administered subcutaneously to Healthy Volunteers
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Must have given written informed consent and be able to comply with all study requirements
- •Healthy males or females aged 18-65 inclusive at the time of Informed Consent
- •Females must be non-pregnant and non-lactating, and either surgically sterile or post- menopausal
- •Males must be surgically sterile, abstinent or using an acceptable contraceptive method
- •BMI <35 kg/m2
Exclusion Criteria
- •Clinically-significant abnormalities in medical history including acute coronary syndrome, major surgery within 3 months of Screening, planned surgery that would occur during the study or physical examination or other screening results such as ECGs at Screening
- •Clinically significant hematologic, chemistry, and urine abnormalities
- •Treatment with another Study Drug, biological agent, or device within 4 weeks of Screening
- •History of bleeding diathesis or coagulopathy
- •Smoking >10 cigarettes per day
- •Considered unsuitable for inclusion by the Principal Investigator
- •Current use of concomitant medications (including herbal or OTC medications) unless approved by Sponsor Medical Monitor
- •Known history or positive test for HIV, hepatitis C or chronic hepatitis B
- •Blood donation within 30 days of screening
Arms & Interventions
Donidalorsen
Ascending single and multiple doses of Donidalorsen administered subcutaneously
Intervention: Donidalorsen (Drug)
Placebo (sterile saline 0.9%)
Calculated volume to match active comparator
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Peak plasma Concentration (Cmax) of Donidalorsen
Time Frame: Up to 176 days
Maximum Donidalorsen plasma concentration, Cmax (ug/mL) will be assessed following SC administration
Time to peak plasma Concentration (Tmax) of Donidalorsen
Time Frame: Up to 176 days
Time to peak Donidalorsen plasma concentration, Tmax (hours) will be assessed following SC administration
Incidence and severity of adverse events that are related to treatment with Donidalorsen
Time Frame: Up to 176 days
The safety and tolerability of multiple doses of Donidalorsen will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with Donidalorsen.
Effects of Donidalorsen on plasma PKK concentration
Time Frame: Up to 176 days
Effects of Donidalorsen on plasma PKK concentration after multiple doses of Donidalorsen compared to baseline
Secondary Outcomes
No secondary outcomes reported