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NCT04916795

A Study To Investigate The Pharmacokinetics, Pharmacodynamics, Safety And Tolerability Of Single Dose Vupanorsen In Healthy Chinese Adults

Completed Phase 1 Results posted Last updated 12 March 2024
What this trial tests

Phase 1 trial testing Vupanorsen in Healthy in 18 participants. Completed in 19 October 2021.

Timeline
17 June 2021
Primary endpoint
19 October 2021
19 October 2021

Quick facts

Lead sponsorPfizer
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposebasic science
Enrollment18
Start date17 June 2021
Primary completion19 October 2021
Estimated completion19 October 2021
Sites1 location across China

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

Adults 18 to 65, any sex, with Healthy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Area Under the Curve (AUC) From Time 0 to 24 Hours Post-dose (AUC24h) for Vupanorsen Primary · 0 hour (predose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on day 1

AUC24h is the area under the concentration-time profile from time 0 to 24 hour post-dose

GroupValue95% CI
Vupanorsen 80 mg3.649± 35
Vupanorsen 160 mg10.82± 42
AUC From Time 0 to 48 Hours Post-dose (AUC48h) for Vupanorsen Primary · 0 hour (predose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post dose

AUC48h is the area under the plasma concentration-time profile from time zero to the quantifiable concentration 48 hours post-dose

GroupValue95% CI
Vupanorsen 80 mg3.699± 34
Vupanorsen 160 mg10.91± 42
AUC From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for Vupanorsen Primary · 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

AUClast is the area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast)

GroupValue95% CI
Vupanorsen 80 mg3.950± 34
Vupanorsen 160 mg11.76± 39
Maximum Observed Concentration (Cmax) Primary · 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

Maximum plasma concentration observed from data

GroupValue95% CI
Vupanorsen 80 mg0.5879± 62
Vupanorsen 160 mg1.810± 63
AUC From Time 0 Extrapolated to Infinite Time (AUCinf) for Vupanorsen Primary · 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

AUCinf is area under the plasma concentration-time profile from time zero extrapolated to infinite time

GroupValue95% CI
Vupanorsen 80 mg4.081± 36
Vupanorsen 160 mg11.91± 39
Time for Cmax (Tmax) for Vupanorsen Primary · 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

Time for Cmax (Tmax) for vupanorsen

GroupValue95% CI
Vupanorsen 80 mg2.001.50 – 3.00
Vupanorsen 160 mg2.001.50 – 3.00
Terminal Elimination Half Life (t½) for Vupanorsen Primary · 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

terminal elimination half life (t½) for vupanorsen

GroupValue95% CI
Vupanorsen 80 mg475.9± 205.50
Vupanorsen 160 mg465.2± 131.50
Apparent Clearance (CL/F) for Vupanorsen Primary · 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

Apparent clearance for vupanorsen

GroupValue95% CI
Vupanorsen 80 mg19.60± 36
Vupanorsen 160 mg13.43± 39
Apparent Volume of Distribution (Vz/F) for Vupanorsen Primary · 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

Apparent volume of distribution for vupanorsen

GroupValue95% CI
Vupanorsen 80 mg12500± 37
Vupanorsen 160 mg8681± 48
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Secondary · Baseline through day 90

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.

All-causality
GroupValue95% CI
Vupanorsen 80 mg3
Vupanorsen 160 mg5
Treatment-related
GroupValue95% CI
Vupanorsen 80 mg2
Vupanorsen 160 mg1
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) Secondary · Baseline through day 90

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.

GroupValue95% CI
Vupanorsen 80 mg5
Vupanorsen 160 mg5
Number of Participants With Clinically Significant Vital Sign Values Secondary · Baseline through day 90

Vital sign data included blood pressure and pulse rate. Clinical significance was assessed by the investigator.

GroupValue95% CI
Vupanorsen 80 mg1
Vupanorsen 160 mg0

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline through day 90. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Vupanorsen 80 mg
Serious: 0/9 (0%)
Deaths: 0/9
Vupanorsen 160 mg
Serious: 0/9 (0%)
Deaths: 0/9
Other adverse events (17 terms — click to expand)

ReactionSystemVupanorsen 80 mgVupanorsen 160 mg
ConjunctivitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
PalpitationsCardiac disorders
Ventricular extrasystolesCardiac disorders
Vitreous haemorrhageEye disorders
Abdominal painGastrointestinal disorders
Mesenteric panniculitisGastrointestinal disorders
ToothacheGastrointestinal disorders
Chest discomfortGeneral disorders
Aspartate aminotransferase increasedInvestigations
Blood uric acid increasedInvestigations
Neutrophil count increasedInvestigations
White blood cell count increasedInvestigations
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
NephrolithiasisRenal and urinary disorders

Data from ClinicalTrials.gov NCT04916795 adverse events section.

Sponsor's own description

This is a Phase 1, randomized, parallel-cohort, open-label study to characterize the pharmacokinetics, pharmacodynamics, safety and tolerability of vupanorsen following 80 mg and 160 mg single subcutaneous dose in healthy Chinese adults with elevated fasting triglyceride.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.
    Liu M, Wang Y, Zhang Y, Hu D, et al · · 2025 · cited 62× · PMID 40059188 · DOI 10.1038/s41392-024-02112-8
  2. RNA Therapeutics: the Next Generation of Drugs for Cardiovascular Diseases.
    Bejar N, Tat TT, Kiss DL. · · 2022 · cited 32× · PMID 35364795 · DOI 10.1007/s11883-022-01007-9
  3. A Randomized, Open-Label, Phase I, Single-Dose Study of Antisense Oligonucleotide, Vupanorsen, in Chinese Adults with Elevated Triglycerides.
    Wu X, Yu J, Ge B, Wang J, et al · · 2024 · cited 3× · PMID 38949758 · DOI 10.1007/s40268-024-00467-5
  4. Targeted Delivery of Nucleic Acid Therapeutics: Emerging Carriers and Applications in Common Metabolic and Inflammatory Diseases.
    Lin X, Chen L, Jia K, Li S, et al · · 2026 · PMID 41869410 · DOI 10.2147/ijn.s566642

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