Trial Outcomes & Findings for A Study To Investigate The Pharmacokinetics, Pharmacodynamics, Safety And Tolerability Of Single Dose Vupanorsen In Healthy Chinese Adults (NCT NCT04916795)
NCT ID: NCT04916795
Last Updated: 2024-03-12
Results Overview
AUC24h is the area under the concentration-time profile from time 0 to 24 hour post-dose
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
18 participants
Primary outcome timeframe
0 hour (predose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on day 1
Results posted on
2024-03-12
Participant Flow
Participant milestones
| Measure |
Vupanorsen 80 mg
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
9
|
|
Overall Study
COMPLETED
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study To Investigate The Pharmacokinetics, Pharmacodynamics, Safety And Tolerability Of Single Dose Vupanorsen In Healthy Chinese Adults
Baseline characteristics by cohort
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
31.44 Years
STANDARD_DEVIATION 7.13 • n=99 Participants
|
36.22 Years
STANDARD_DEVIATION 8.45 • n=107 Participants
|
33.83 Years
STANDARD_DEVIATION 7.97 • n=206 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
9 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 0 hour (predose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on day 1Population: The analysis population refers to all participants enrolled and treated who had at least 1 of the vupanorsen pharmacokinetic (PK) parameters of primary interest.
AUC24h is the area under the concentration-time profile from time 0 to 24 hour post-dose
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Area Under the Curve (AUC) From Time 0 to 24 Hours Post-dose (AUC24h) for Vupanorsen
|
3.649 microgram*hour per milliliter(mcg*hr/mL)
Geometric Coefficient of Variation 35
|
10.82 microgram*hour per milliliter(mcg*hr/mL)
Geometric Coefficient of Variation 42
|
PRIMARY outcome
Timeframe: 0 hour (predose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post dosePopulation: The analysis population refers to all participants enrolled and treated who had at least 1 of the vupanorsen PK parameters of primary interest.
AUC48h is the area under the plasma concentration-time profile from time zero to the quantifiable concentration 48 hours post-dose
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
AUC From Time 0 to 48 Hours Post-dose (AUC48h) for Vupanorsen
|
3.699 mcg*hr/mL
Geometric Coefficient of Variation 34
|
10.91 mcg*hr/mL
Geometric Coefficient of Variation 42
|
PRIMARY outcome
Timeframe: 0 hour (predose), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours post dose, and on days 8, 15, 30, 60 and 90Population: The analysis population refers to all participants enrolled and treated who had at least 1 of the vupanorsen PK parameters of primary interest.
AUClast is the area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast)
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
AUC From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for Vupanorsen
|
3.950 mcg*hr/mL
Geometric Coefficient of Variation 34
|
11.76 mcg*hr/mL
Geometric Coefficient of Variation 39
|
PRIMARY outcome
Timeframe: 0 hour (predose), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours post dose, and on days 8, 15, 30, 60 and 90Population: The analysis population refers to all participants enrolled and treated who had at least 1 of the vupanorsen PK parameters of primary interest.
Maximum plasma concentration observed from data
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Maximum Observed Concentration (Cmax)
|
0.5879 microgram per milliliter (μg/mL)
Geometric Coefficient of Variation 62
|
1.810 microgram per milliliter (μg/mL)
Geometric Coefficient of Variation 63
|
PRIMARY outcome
Timeframe: 0 hour (predose), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours post dose, and on days 8, 15, 30, 60 and 90Population: The analysis population refers to all participants enrolled and treated who had at least 1 of the vupanorsen PK parameters of primary interest.
AUCinf is area under the plasma concentration-time profile from time zero extrapolated to infinite time
Outcome measures
| Measure |
Vupanorsen 80 mg
n=8 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
AUC From Time 0 Extrapolated to Infinite Time (AUCinf) for Vupanorsen
|
4.081 mcg*hr/mL
Geometric Coefficient of Variation 36
|
11.91 mcg*hr/mL
Geometric Coefficient of Variation 39
|
PRIMARY outcome
Timeframe: 0 hour (predose), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours post dose, and on days 8, 15, 30, 60 and 90Population: The analysis population refers to all participants enrolled and treated who had at least 1 of the vupanorsen PK parameters of primary interest.
Time for Cmax (Tmax) for vupanorsen
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Time for Cmax (Tmax) for Vupanorsen
|
2.00 hour (hr)
Interval 1.5 to 3.0
|
2.00 hour (hr)
Interval 1.5 to 3.0
|
PRIMARY outcome
Timeframe: 0 hour (predose), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours post dose, and on days 8, 15, 30, 60 and 90Population: The analysis population refers to all participants enrolled and treated who had at least 1 of the vupanorsen PK parameters of primary interest.
terminal elimination half life (t½) for vupanorsen
Outcome measures
| Measure |
Vupanorsen 80 mg
n=8 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Terminal Elimination Half Life (t½) for Vupanorsen
|
475.9 hour (hr)
Standard Deviation 205.50
|
465.2 hour (hr)
Standard Deviation 131.50
|
PRIMARY outcome
Timeframe: 0 hour (predose), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours post dose, and on days 8, 15, 30, 60 and 90Population: The analysis population refers to all participants enrolled and treated who had at least 1 of the vupanorsen PK parameters of primary interest.
Apparent clearance for vupanorsen
Outcome measures
| Measure |
Vupanorsen 80 mg
n=8 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Apparent Clearance (CL/F) for Vupanorsen
|
19.60 liter per hour (L/hr)
Geometric Coefficient of Variation 36
|
13.43 liter per hour (L/hr)
Geometric Coefficient of Variation 39
|
PRIMARY outcome
Timeframe: 0 hour (predose), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours post dose, and on days 8, 15, 30, 60 and 90Population: The analysis population refers to all participants enrolled and treated who had at least 1 of the vupanorsen PK parameters of primary interest.
Apparent volume of distribution for vupanorsen
Outcome measures
| Measure |
Vupanorsen 80 mg
n=8 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Apparent Volume of Distribution (Vz/F) for Vupanorsen
|
12500 liter (L)
Geometric Coefficient of Variation 37
|
8681 liter (L)
Geometric Coefficient of Variation 48
|
SECONDARY outcome
Timeframe: Baseline through day 90Population: All participants enrolled and who took at least 1 dose of study intervention.
Adverse events (AEs): any untoward medical occurrence in a clinical investigation participant administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. AEs included SAEs and non-serious AEs. Treatment-related TEAEs were any untoward medical occurrence attributed to study treatment. Causality to study treatment was determined by the investigator.
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
All-causality
|
3 Participants
|
5 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Treatment-related
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline through day 90Population: All participants enrolled and who took at least 1 dose of study intervention.
Protocol-required safety laboratory assessments included chemistry, hematology, and urinalysis (and microscopy, if needed). Each parameter was evaluated against commonly used and widely accepted criteria.
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
|
5 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline through day 90Population: All participants enrolled and who took at least 1 dose of study intervention.
Vital sign data included blood pressure and pulse rate. Clinical significance was assessed by the investigator.
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Number of Participants With Clinically Significant Vital Sign Values
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline through day 90Population: All participants enrolled and who took at least 1 dose of study intervention.
Clinical significance of ECG data was assessed by the investigator.
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90Population: All participants enrolled and treated who had at least 1 of the pharmacodynamic (PD) parameters of interest.
Percent changes from baseline in ANGPTL3 on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3)
DAY2
|
-13.88 percent change (%)
Standard Deviation 18.644
|
-22.14 percent change (%)
Standard Deviation 15.103
|
|
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3)
DAY3
|
-32.65 percent change (%)
Standard Deviation 22.375
|
-43.56 percent change (%)
Standard Deviation 15.151
|
|
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3)
DAY8
|
-59.65 percent change (%)
Standard Deviation 18.727
|
-69.11 percent change (%)
Standard Deviation 13.462
|
|
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3)
DAY15
|
-54.07 percent change (%)
Standard Deviation 21.893
|
-69.48 percent change (%)
Standard Deviation 11.659
|
|
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3)
DAY30
|
-48.66 percent change (%)
Standard Deviation 21.921
|
-62.81 percent change (%)
Standard Deviation 18.873
|
|
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3)
DAY60
|
-38.54 percent change (%)
Standard Deviation 23.440
|
-53.33 percent change (%)
Standard Deviation 11.830
|
|
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3)
DAY90
|
-12.69 percent change (%)
Standard Deviation 20.238
|
-29.72 percent change (%)
Standard Deviation 15.587
|
SECONDARY outcome
Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90Population: All participants enrolled and treated who had at least 1 of the PD parameters of interest.
Percentage changes from baseline in total cholesterol on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Percent Change From Baseline in Total Cholesterol
DAY2
|
-1.50 percent change (%)
Standard Deviation 5.839
|
-2.04 percent change (%)
Standard Deviation 6.238
|
|
Percent Change From Baseline in Total Cholesterol
DAY3
|
-1.71 percent change (%)
Standard Deviation 9.012
|
-0.71 percent change (%)
Standard Deviation 7.665
|
|
Percent Change From Baseline in Total Cholesterol
DAY8
|
-18.89 percent change (%)
Standard Deviation 6.814
|
-20.39 percent change (%)
Standard Deviation 8.526
|
|
Percent Change From Baseline in Total Cholesterol
DAY15
|
-19.57 percent change (%)
Standard Deviation 12.554
|
-21.85 percent change (%)
Standard Deviation 11.371
|
|
Percent Change From Baseline in Total Cholesterol
DAY30
|
-10.46 percent change (%)
Standard Deviation 14.303
|
-11.11 percent change (%)
Standard Deviation 7.976
|
|
Percent Change From Baseline in Total Cholesterol
DAY60
|
-8.26 percent change (%)
Standard Deviation 16.712
|
-1.76 percent change (%)
Standard Deviation 10.038
|
|
Percent Change From Baseline in Total Cholesterol
DAY90
|
-5.10 percent change (%)
Standard Deviation 14.122
|
-3.06 percent change (%)
Standard Deviation 7.317
|
SECONDARY outcome
Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90Population: All participants enrolled and treated who had at least 1 of the PD parameters of interest.
Percentage changes from baseline in HDL-C on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
DAY2
|
-0.55 percent change (%)
Standard Deviation 3.636
|
-0.79 percent change (%)
Standard Deviation 8.504
|
|
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
DAY3
|
-3.81 percent change (%)
Standard Deviation 2.908
|
-0.14 percent change (%)
Standard Deviation 9.771
|
|
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
DAY8
|
-3.97 percent change (%)
Standard Deviation 13.335
|
-9.16 percent change (%)
Standard Deviation 16.834
|
|
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
DAY15
|
-3.33 percent change (%)
Standard Deviation 20.205
|
-10.08 percent change (%)
Standard Deviation 16.485
|
|
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
DAY30
|
8.96 percent change (%)
Standard Deviation 18.824
|
3.70 percent change (%)
Standard Deviation 15.475
|
|
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
DAY60
|
8.19 percent change (%)
Standard Deviation 13.457
|
5.18 percent change (%)
Standard Deviation 15.265
|
|
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
DAY90
|
6.74 percent change (%)
Standard Deviation 14.464
|
5.92 percent change (%)
Standard Deviation 12.033
|
SECONDARY outcome
Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90Population: All participants enrolled and treated who had at least 1 of the PD parameters of interest.
Percentage changes from baseline in LDL-C on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
DAY90
|
-7.42 percent change (%)
Standard Deviation 19.649
|
2.97 percent change (%)
Standard Deviation 10.818
|
|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
DAY2
|
2.94 percent change (%)
Standard Deviation 9.247
|
-0.63 percent change (%)
Standard Deviation 7.817
|
|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
DAY3
|
1.91 percent change (%)
Standard Deviation 12.944
|
2.80 percent change (%)
Standard Deviation 11.548
|
|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
DAY8
|
-14.65 percent change (%)
Standard Deviation 9.005
|
-12.10 percent change (%)
Standard Deviation 15.647
|
|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
DAY15
|
-14.95 percent change (%)
Standard Deviation 19.076
|
-15.93 percent change (%)
Standard Deviation 16.486
|
|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
DAY30
|
-9.86 percent change (%)
Standard Deviation 22.385
|
-6.03 percent change (%)
Standard Deviation 16.710
|
|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
DAY60
|
-12.77 percent change (%)
Standard Deviation 23.668
|
0.19 percent change (%)
Standard Deviation 15.380
|
SECONDARY outcome
Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90Population: All participants enrolled and treated who had at least 1 of the PD parameters of interest.
Percentage changes from baseline in VLDL-C on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C)
DAY2
|
-15.93 percent change (%)
Standard Deviation 18.320
|
-1.16 percent change (%)
Standard Deviation 28.947
|
|
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C)
DAY3
|
5.68 percent change (%)
Standard Deviation 35.419
|
-4.79 percent change (%)
Standard Deviation 45.277
|
|
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C)
DAY8
|
-65.66 percent change (%)
Standard Deviation 19.581
|
-72.26 percent change (%)
Standard Deviation 21.036
|
|
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C)
DAY15
|
-62.44 percent change (%)
Standard Deviation 27.207
|
-64.24 percent change (%)
Standard Deviation 31.482
|
|
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C)
DAY30
|
-27.64 percent change (%)
Standard Deviation 40.099
|
-53.51 percent change (%)
Standard Deviation 27.018
|
|
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C)
DAY60
|
11.09 percent change (%)
Standard Deviation 50.942
|
8.28 percent change (%)
Standard Deviation 77.143
|
|
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C)
DAY90
|
-22.63 percent change (%)
Standard Deviation 58.405
|
-51.39 percent change (%)
Standard Deviation 37.174
|
SECONDARY outcome
Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90Population: All participants enrolled and treated who had at least 1 of the PD parameters of interest.
Percentage changes from baseline in triglyceride on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Percent Change From Baseline in Triglyceride
DAY2
|
-9.72 percent change (%)
Standard Deviation 15.235
|
-5.86 percent change (%)
Standard Deviation 12.887
|
|
Percent Change From Baseline in Triglyceride
DAY3
|
-10.03 percent change (%)
Standard Deviation 16.856
|
-7.24 percent change (%)
Standard Deviation 26.804
|
|
Percent Change From Baseline in Triglyceride
DAY8
|
-32.61 percent change (%)
Standard Deviation 16.422
|
-52.47 percent change (%)
Standard Deviation 18.150
|
|
Percent Change From Baseline in Triglyceride
DAY15
|
-41.91 percent change (%)
Standard Deviation 19.992
|
-48.19 percent change (%)
Standard Deviation 16.491
|
|
Percent Change From Baseline in Triglyceride
DAY30
|
-28.54 percent change (%)
Standard Deviation 20.289
|
-44.14 percent change (%)
Standard Deviation 19.466
|
|
Percent Change From Baseline in Triglyceride
DAY60
|
-19.55 percent change (%)
Standard Deviation 29.981
|
-30.60 percent change (%)
Standard Deviation 23.585
|
|
Percent Change From Baseline in Triglyceride
DAY90
|
7.26 percent change (%)
Standard Deviation 59.830
|
-21.26 percent change (%)
Standard Deviation 28.335
|
SECONDARY outcome
Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90Population: All participants enrolled and treated who had at least 1 of the PD parameters of interest.
Percentage changes from baseline in non-HDL on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Outcome measures
| Measure |
Vupanorsen 80 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 Participants
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
DAY2
|
-1.39 percent change (%)
Standard Deviation 7.609
|
-2.40 percent change (%)
Standard Deviation 6.649
|
|
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
DAY3
|
-0.12 percent change (%)
Standard Deviation 12.865
|
-0.89 percent change (%)
Standard Deviation 9.120
|
|
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
DAY8
|
-22.58 percent change (%)
Standard Deviation 8.362
|
-23.41 percent change (%)
Standard Deviation 8.368
|
|
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
DAY15
|
-23.18 percent change (%)
Standard Deviation 15.173
|
-25.37 percent change (%)
Standard Deviation 11.202
|
|
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
DAY30
|
-15.33 percent change (%)
Standard Deviation 16.925
|
-15.58 percent change (%)
Standard Deviation 10.089
|
|
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
DAY60
|
-11.58 percent change (%)
Standard Deviation 22.194
|
-3.89 percent change (%)
Standard Deviation 9.669
|
|
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
DAY90
|
-8.32 percent change (%)
Standard Deviation 16.806
|
-6.35 percent change (%)
Standard Deviation 7.602
|
SECONDARY outcome
Timeframe: Day 1, Day 15, Day 60, and Day 90Population: Study endpoint of percent changes from baseline in apolipoprotein A-1 (ApoA-I),apolipoprotein B (ApoB) total (including ApoB-48, ApoB-100), and apolipoprotein C-III (ApoC-III) on Day 15, Day 60, and Day 90, were terminated due to changes of development plan. No data were collected for these terminated endpoints.
Percentage changes from baseline in ApoA-I on Day 15, Day 60, and Day 90. This endpoint was terminated due to changes of development plan.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1, Day 15, Day 60, and Day 90Population: Study endpoint of percent changes from baseline in apolipoprotein A-1 (ApoA-I),apolipoprotein B (ApoB) total (including ApoB-48, ApoB-100), and apolipoprotein C-III (ApoC-III) on Day 15, Day 60, and Day 90, were terminated due to changes of development plan. No data were collected for these terminated endpoints.
Percentage changes from baseline in ApoB total (including ApoB-48, ApoB-100) on Day 15, Day 60, and Day 90. This endpoint was terminated due to changes of development plan.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1, Day 15, Day 60, and Day 90Population: Study endpoint of percent changes from baseline in apolipoprotein A-1 (ApoA-I),apolipoprotein B (ApoB) total (including ApoB-48, ApoB-100), and apolipoprotein C-III (ApoC-III) on Day 15, Day 60, and Day 90, were terminated due to changes of development plan. No data were collected for these terminated endpoints.
Percentage changes from baseline in apolipoprotein C-III (ApoC-III) on Day 15, Day 60, and Day 90. This endpoint was terminated due to changes of development plan.
Outcome measures
Outcome data not reported
Adverse Events
Vupanorsen 80 mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Vupanorsen 160 mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Vupanorsen 80 mg
n=9 participants at risk
Participants were selected and categorized into the Vupanorsen 80 mg group and received a single 80 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
Vupanorsen 160 mg
n=9 participants at risk
Participants were selected and categorized into the Vupanorsen 160 mg group and received a single 160 mg subcutaneous dose of vupanorsen on Day 1, followed by an on-site post-treatment evaluation on Days 8, 15, 30, 60 and 90.
|
|---|---|---|
|
Cardiac disorders
Palpitations
|
11.1%
1/9 • Baseline through day 90
|
0.00%
0/9 • Baseline through day 90
|
|
Cardiac disorders
Ventricular extrasystoles
|
11.1%
1/9 • Baseline through day 90
|
0.00%
0/9 • Baseline through day 90
|
|
Eye disorders
Vitreous haemorrhage
|
0.00%
0/9 • Baseline through day 90
|
11.1%
1/9 • Baseline through day 90
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/9 • Baseline through day 90
|
11.1%
1/9 • Baseline through day 90
|
|
Gastrointestinal disorders
Mesenteric panniculitis
|
0.00%
0/9 • Baseline through day 90
|
11.1%
1/9 • Baseline through day 90
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/9 • Baseline through day 90
|
11.1%
1/9 • Baseline through day 90
|
|
General disorders
Chest discomfort
|
11.1%
1/9 • Baseline through day 90
|
0.00%
0/9 • Baseline through day 90
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/9 • Baseline through day 90
|
22.2%
2/9 • Baseline through day 90
|
|
Infections and infestations
Upper respiratory tract infection
|
22.2%
2/9 • Baseline through day 90
|
11.1%
1/9 • Baseline through day 90
|
|
Investigations
Alanine aminotransferase increased
|
22.2%
2/9 • Baseline through day 90
|
0.00%
0/9 • Baseline through day 90
|
|
Investigations
Aspartate aminotransferase increased
|
11.1%
1/9 • Baseline through day 90
|
0.00%
0/9 • Baseline through day 90
|
|
Investigations
Blood uric acid increased
|
0.00%
0/9 • Baseline through day 90
|
11.1%
1/9 • Baseline through day 90
|
|
Investigations
Neutrophil count increased
|
0.00%
0/9 • Baseline through day 90
|
11.1%
1/9 • Baseline through day 90
|
|
Investigations
White blood cell count increased
|
11.1%
1/9 • Baseline through day 90
|
0.00%
0/9 • Baseline through day 90
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
11.1%
1/9 • Baseline through day 90
|
0.00%
0/9 • Baseline through day 90
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/9 • Baseline through day 90
|
11.1%
1/9 • Baseline through day 90
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/9 • Baseline through day 90
|
11.1%
1/9 • Baseline through day 90
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER