Elevated Triglycerides (TG) Clinical Trial
Official title:
Placebo-Controlled, Dose-Escalation Study to Assess Safety, Tolerability, PK and PD of a GalNAc3 Conjugated Antisense Oligonucleotide Targeting ApoC-III, Administered Subcutaneously to Healthy Volunteers With Elevated Triglycerides
| Verified date | May 2018 |
| Source | Ionis Pharmaceuticals, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS APOC-III-LRx given to healthy volunteer subjects.
| Status | Completed |
| Enrollment | 56 |
| Est. completion date | April 30, 2018 |
| Est. primary completion date | April 30, 2018 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 18 Years to 65 Years |
| Eligibility |
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 - 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 < 35.0 kg/m2 - Subjects must have Fasting TG = 90 mg/dL or = 200 mg/dL depending on Cohort assignment Exclusion Criteria: - Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B - Treatment with another Study Drug, biological agent, or device within one-month of screening - Regular excessive use of alcohol within 6 months of Screening - Use of concomitant drugs unless authorized by the Sponsor Medical Monitor - Smoking > 10 cigarettes a day - Considered unsuitable for inclusion by the Principal Investigator |
| Country | Name | City | State |
|---|---|---|---|
| Canada | BioPharma Services | Toronto | Ontario |
| Lead Sponsor | Collaborator |
|---|---|
| Ionis Pharmaceuticals, Inc. | Akcea Therapeutics |
Canada,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx | Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with plasma apolipoprotein C-III (apoC-III) compared to baseline. | Up to 183 days | |
| Other | Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx | Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with TG compared to baseline. | Up to 183 days | |
| Other | Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx | Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with total cholesterol (TC) compared to baseline. | Up to 183 days | |
| Other | Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx | Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with low density lipoprotein cholesterol (LDL-C) compared to baseline. | Up to 183 days | |
| Other | Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx | Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with high density lipoprotein cholesterol (HDL-C) compared to baseline. | Up to 183 days | |
| Other | Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx | Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with non-high density lipoprotein cholesterol (non-HDL-C) compared to baseline. | Up to 183 days | |
| Other | Exploratory pharmacodynamic effects of IONIS-APOC-III-LRx | Effects of IONIS-APOC-III-LRx on changes in levels of oxidized phospholipids associated with very low density lipoprotein cholesterol (VLDL-C) compared to baseline. | Up to 183 days | |
| Primary | To evaluate the safety and tolerability of single and multiple doses of IONIS- APOC-III-LRx - (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters) | The safety and tolerability of IONIS- APOC-III-LRx will be assessed by determining the incidence, severity, and dose relationship of adverse effects and changes in the laboratory parameters by dose. Safety results in subjects dosed with IONIS APOC-III-LRx will be compared with those from subjects dosed with placebo. | Up to 183 days | |
| Secondary | To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx | The maximum area under the curve (AUC) of IONIS- APOC-III-LRx will be assessed following single and multiple- dose SC administration | Up to 183 days | |
| Secondary | To evaluate the urine pharmacokinetics of single and multiple doses of IONIS¬-APOC-III-LRx | The amount of IONIS-APOC-III-LRx excreted in urine at selected 24-hour intervals [Ae0-24h] will be determined. | Up to 183 days | |
| Secondary | To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx | The maximum plasma concentration (Cmax) of IONIS- APOC-III-LRx will be assessed following single and multiple- dose SC administration | Up to 183 Days | |
| Secondary | To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx | The maximum time to Cmax (Tmax) of IONIS- APOC-III-LRx will be assessed following single and multiple-dose SC administration | Up to 183 days |