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

NCT03263507 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ISIS 721744-CS1
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteers

Keywords

IONIS PKK-LRx

Outcome Measures

Primary Outcomes (4)

• Incidence and severity of adverse events that are related to treatment with Donidalorsen

  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.

  Up to 176 days

• Peak plasma Concentration (Cmax) of Donidalorsen

  Maximum Donidalorsen plasma concentration, Cmax (ug/mL) will be assessed following SC administration

  Up to 176 days

• Time to peak plasma Concentration (Tmax) of Donidalorsen

  Time to peak Donidalorsen plasma concentration, Tmax (hours) will be assessed following SC administration

  Up to 176 days

• Effects of Donidalorsen on plasma PKK concentration

  Effects of Donidalorsen on plasma PKK concentration after multiple doses of Donidalorsen compared to baseline

  Up to 176 days

Study Arms (2)

Donidalorsen

EXPERIMENTAL

Ascending single and multiple doses of Donidalorsen administered subcutaneously

Drug: Donidalorsen

Placebo (sterile saline 0.9%)

PLACEBO COMPARATOR

Calculated volume to match active comparator

Drug: Placebo

Interventions

Placebo DRUG

Saline .9%

Placebo (sterile saline 0.9%)

Donidalorsen DRUG

Donidalorsen administered subcutaneously

Also known as: ISIS 721744, IONIS-PKK-LRx

Donidalorsen

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (1)

Ionis Investigative Site

Toronto, Ontario, M9L 3A2, Canada

Location

MeSH Terms

Interventions

donidalorsen; IONIS-PKK-LRx

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: August 28, 2017
• Study Start: August 28, 2017
• Primary Completion: October 9, 2018
• Study Completion: October 9, 2018
• Last Updated: August 4, 2022

Record last verified: 2022-08

Locations

CA (1)