Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Donidalorsen (IONIS-PKK-LRx) Administered Subcutaneously to Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: Placebo; Drug: Donidalorsen

• Registration Number: NCT03263507
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

The purpose is to assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Donidalorsen administered subcutaneously to Healthy Volunteers

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-08-17
• Study First Submitted QC: 2017-08-23
• Study Start: 2017-08-28
• Study First Posted: 2017-08-28
• Primary Completion: 2018-10-09
• Study Completion: 2018-10-09
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-02
• Last Update Posted: 2022-08-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo (sterile saline 0.9%)	Placebo	Calculated volume to match active comparator
Donidalorsen	Donidalorsen	Ascending single and multiple doses of Donidalorsen administered subcutaneously

Primary Outcome Measures

Name	Time	Method
Peak plasma Concentration (Cmax) of Donidalorsen	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	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	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	Up to 176 days	Effects of Donidalorsen on plasma PKK concentration after multiple doses of Donidalorsen compared to baseline

Trial Locations

Locations (1)

Ionis Investigative Site; 🇨🇦 Toronto, Ontario, Canada