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=5 Participants	36.22 Years STANDARD_DEVIATION 8.45 • n=7 Participants	33.83 Years STANDARD_DEVIATION 7.97 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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

Population: 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 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.	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.
Area Under the Curve (AUC) From Time 0 to 24 Hours Post-dose (AUC24h) for Vupanorsen	10.82 microgram*hour per milliliter(mcg*hr/mL) Geometric Coefficient of Variation 42	3.649 microgram*hour per milliliter(mcg*hr/mL) Geometric Coefficient of Variation 35

PRIMARY outcome

Timeframe: 0 hour (predose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post dose

Population: 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 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.	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.
AUC From Time 0 to 48 Hours Post-dose (AUC48h) for Vupanorsen	10.91 mcg*hr/mL Geometric Coefficient of Variation 42	3.699 mcg*hr/mL Geometric Coefficient of Variation 34

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 90

Population: 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 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.	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.
AUC From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for Vupanorsen	11.76 mcg*hr/mL Geometric Coefficient of Variation 39	3.950 mcg*hr/mL Geometric Coefficient of Variation 34

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 90

Population: 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 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.	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.
Maximum Observed Concentration (Cmax)	1.810 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 63	0.5879 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 62

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 90

Population: 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 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.	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.
AUC From Time 0 Extrapolated to Infinite Time (AUCinf) for Vupanorsen	11.91 mcg*hr/mL Geometric Coefficient of Variation 39	4.081 mcg*hr/mL Geometric Coefficient of Variation 36

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 90

Population: 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 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.	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.
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 90

Population: 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 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.	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.
Terminal Elimination Half Life (t½) for Vupanorsen	465.2 hour (hr) Standard Deviation 131.50	475.9 hour (hr) Standard Deviation 205.50

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 90

Population: 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 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.	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.
Apparent Clearance (CL/F) for Vupanorsen	13.43 liter per hour (L/hr) Geometric Coefficient of Variation 39	19.60 liter per hour (L/hr) Geometric Coefficient of Variation 36

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 90

Population: 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 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.	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.
Apparent Volume of Distribution (Vz/F) for Vupanorsen	8681 liter (L) Geometric Coefficient of Variation 48	12500 liter (L) Geometric Coefficient of Variation 37

SECONDARY outcome

Timeframe: Baseline through day 90

Population: 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 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.	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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) All-causality	5 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treatment-related	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline through day 90

Population: 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 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.	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.
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	5 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline through day 90

Population: 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 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.	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.
Number of Participants With Clinically Significant Vital Sign Values	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline through day 90

Population: 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 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.	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.
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 90

Population: 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 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.	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.
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3) DAY15	-69.48 percent change (%) Standard Deviation 11.659	-54.07 percent change (%) Standard Deviation 21.893
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3) DAY2	-22.14 percent change (%) Standard Deviation 15.103	-13.88 percent change (%) Standard Deviation 18.644
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3) DAY3	-43.56 percent change (%) Standard Deviation 15.151	-32.65 percent change (%) Standard Deviation 22.375
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3) DAY8	-69.11 percent change (%) Standard Deviation 13.462	-59.65 percent change (%) Standard Deviation 18.727
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3) DAY30	-62.81 percent change (%) Standard Deviation 18.873	-48.66 percent change (%) Standard Deviation 21.921
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3) DAY60	-53.33 percent change (%) Standard Deviation 11.830	-38.54 percent change (%) Standard Deviation 23.440
Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3) DAY90	-29.72 percent change (%) Standard Deviation 15.587	-12.69 percent change (%) Standard Deviation 20.238

SECONDARY outcome

Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

Population: 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 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.	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.
Percent Change From Baseline in Total Cholesterol DAY3	-0.71 percent change (%) Standard Deviation 7.665	-1.71 percent change (%) Standard Deviation 9.012
Percent Change From Baseline in Total Cholesterol DAY8	-20.39 percent change (%) Standard Deviation 8.526	-18.89 percent change (%) Standard Deviation 6.814
Percent Change From Baseline in Total Cholesterol DAY60	-1.76 percent change (%) Standard Deviation 10.038	-8.26 percent change (%) Standard Deviation 16.712
Percent Change From Baseline in Total Cholesterol DAY90	-3.06 percent change (%) Standard Deviation 7.317	-5.10 percent change (%) Standard Deviation 14.122
Percent Change From Baseline in Total Cholesterol DAY2	-2.04 percent change (%) Standard Deviation 6.238	-1.50 percent change (%) Standard Deviation 5.839
Percent Change From Baseline in Total Cholesterol DAY15	-21.85 percent change (%) Standard Deviation 11.371	-19.57 percent change (%) Standard Deviation 12.554
Percent Change From Baseline in Total Cholesterol DAY30	-11.11 percent change (%) Standard Deviation 7.976	-10.46 percent change (%) Standard Deviation 14.303

SECONDARY outcome

Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

Population: 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 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.	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.
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C) DAY2	-0.79 percent change (%) Standard Deviation 8.504	-0.55 percent change (%) Standard Deviation 3.636
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C) DAY3	-0.14 percent change (%) Standard Deviation 9.771	-3.81 percent change (%) Standard Deviation 2.908
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C) DAY8	-9.16 percent change (%) Standard Deviation 16.834	-3.97 percent change (%) Standard Deviation 13.335
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C) DAY15	-10.08 percent change (%) Standard Deviation 16.485	-3.33 percent change (%) Standard Deviation 20.205
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C) DAY30	3.70 percent change (%) Standard Deviation 15.475	8.96 percent change (%) Standard Deviation 18.824
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C) DAY60	5.18 percent change (%) Standard Deviation 15.265	8.19 percent change (%) Standard Deviation 13.457
Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C) DAY90	5.92 percent change (%) Standard Deviation 12.033	6.74 percent change (%) Standard Deviation 14.464

SECONDARY outcome

Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

Population: 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 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.	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.
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) DAY3	2.80 percent change (%) Standard Deviation 11.548	1.91 percent change (%) Standard Deviation 12.944
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) DAY8	-12.10 percent change (%) Standard Deviation 15.647	-14.65 percent change (%) Standard Deviation 9.005
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) DAY15	-15.93 percent change (%) Standard Deviation 16.486	-14.95 percent change (%) Standard Deviation 19.076
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) DAY30	-6.03 percent change (%) Standard Deviation 16.710	-9.86 percent change (%) Standard Deviation 22.385
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) DAY2	-0.63 percent change (%) Standard Deviation 7.817	2.94 percent change (%) Standard Deviation 9.247
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) DAY60	0.19 percent change (%) Standard Deviation 15.380	-12.77 percent change (%) Standard Deviation 23.668
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) DAY90	2.97 percent change (%) Standard Deviation 10.818	-7.42 percent change (%) Standard Deviation 19.649

SECONDARY outcome

Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

Population: 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 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.	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.
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) DAY2	-1.16 percent change (%) Standard Deviation 28.947	-15.93 percent change (%) Standard Deviation 18.320
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) DAY3	-4.79 percent change (%) Standard Deviation 45.277	5.68 percent change (%) Standard Deviation 35.419
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) DAY8	-72.26 percent change (%) Standard Deviation 21.036	-65.66 percent change (%) Standard Deviation 19.581
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) DAY15	-64.24 percent change (%) Standard Deviation 31.482	-62.44 percent change (%) Standard Deviation 27.207
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) DAY30	-53.51 percent change (%) Standard Deviation 27.018	-27.64 percent change (%) Standard Deviation 40.099
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) DAY60	8.28 percent change (%) Standard Deviation 77.143	11.09 percent change (%) Standard Deviation 50.942
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) DAY90	-51.39 percent change (%) Standard Deviation 37.174	-22.63 percent change (%) Standard Deviation 58.405

SECONDARY outcome

Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

Population: 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 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.	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.
Percent Change From Baseline in Triglyceride DAY2	-5.86 percent change (%) Standard Deviation 12.887	-9.72 percent change (%) Standard Deviation 15.235
Percent Change From Baseline in Triglyceride DAY3	-7.24 percent change (%) Standard Deviation 26.804	-10.03 percent change (%) Standard Deviation 16.856
Percent Change From Baseline in Triglyceride DAY8	-52.47 percent change (%) Standard Deviation 18.150	-32.61 percent change (%) Standard Deviation 16.422
Percent Change From Baseline in Triglyceride DAY15	-48.19 percent change (%) Standard Deviation 16.491	-41.91 percent change (%) Standard Deviation 19.992
Percent Change From Baseline in Triglyceride DAY30	-44.14 percent change (%) Standard Deviation 19.466	-28.54 percent change (%) Standard Deviation 20.289
Percent Change From Baseline in Triglyceride DAY60	-30.60 percent change (%) Standard Deviation 23.585	-19.55 percent change (%) Standard Deviation 29.981
Percent Change From Baseline in Triglyceride DAY90	-21.26 percent change (%) Standard Deviation 28.335	7.26 percent change (%) Standard Deviation 59.830

SECONDARY outcome

Timeframe: Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

Population: 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 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.	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.
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) DAY2	-2.40 percent change (%) Standard Deviation 6.649	-1.39 percent change (%) Standard Deviation 7.609
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) DAY3	-0.89 percent change (%) Standard Deviation 9.120	-0.12 percent change (%) Standard Deviation 12.865
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) DAY8	-23.41 percent change (%) Standard Deviation 8.368	-22.58 percent change (%) Standard Deviation 8.362
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) DAY15	-25.37 percent change (%) Standard Deviation 11.202	-23.18 percent change (%) Standard Deviation 15.173
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) DAY30	-15.58 percent change (%) Standard Deviation 10.089	-15.33 percent change (%) Standard Deviation 16.925
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) DAY60	-3.89 percent change (%) Standard Deviation 9.669	-11.58 percent change (%) Standard Deviation 22.194
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) DAY90	-6.35 percent change (%) Standard Deviation 7.602	-8.32 percent change (%) Standard Deviation 16.806

SECONDARY outcome

Timeframe: Day 1, Day 15, Day 60, and Day 90

Population: 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 90

Population: 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 90

Population: 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

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

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