AzTrials
AzTrials

HealthyPhase 1NCT04916795

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

A Phase 1 study testing Vupanorsen in people with Healthy, run by Pfizer at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Vupanorsen
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteChina
Study dates
17 Jun 2021to 19 Oct 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Male and female Chinese participants must be 18 to 65 years of age, inclusive, at the time of signing the ICD.
  • Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants.
  • Chinese participant is defined as individuals currently residing in mainland China who were born in China and have both parents of Chinese descent.
  • Male and female Chinese participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests (except for TG levels), and 12-lead ECG monitoring.
  • Fasting TG ≥ 90 mg/dL at Screening (up to 1 repeat allowed for TG and the second TG value will be used for the eligibility).
  • Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
  • BMI of 17.5 to 35.0 kg/m2; and a total body weight >50 kg (110 lb).
  • Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Who cannot join

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
  • History of human immunodeficiency virus (HIV) infection, syphilis, hepatitis B, or hepatitis C; positive testing for HIV, syphilis, HBsAg, or HCVAb. Prior Hepatitis B vaccination is allowed.
  • Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
  • Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.
  • Previous administration with an investigational drug within 4 months or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
  • A positive urine drug test.
Show all 18Show fewer
  • Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
  • Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTc interval >450 msec, complete LBBB, signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is >450 msec, this interval should be rate-corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants.
  • Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary:
  • AST or ALT level ≥1.25 × ULN;
  • Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is≤ ULN.
  • History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).
  • Blood donation (excluding plasma donations) of approximately 400 mL or more within 60 days prior to dosing.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • History of substance abuse within 12 months of the screening visit.
  • Pregnant females; breastfeeding females.
  • Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
  • Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Huashan Hospital,Fudan University

    Shanghai, Shanghai Municipality, 201107

Other trials in China

About this study

Official title: A PHASE 1, RANDOMIZED, OPEN-LABEL, SINGLE DOSE STUDY TO INVESTIGATE THE PHARMACOKINETICS, PHARMACODYNAMICS, SAFETY AND TOLERABILITY OF VUPANORSEN ADMINISTERED SUBCUTANEOUSLY TO HEALTHY CHINESE ADULTS

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.

Conditions
Healthy
Being tested
Vupanorsen

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VupanorsenDrug

    80 mg subcutaneous injection

  • VupanorsenDrug

    80 mg subcutaneous injection

Study groups in NCT04916795
Study groupRoleWhat they receive
Vupanorsen 80 milligram (mg)ExperimentalParticipants will receive one, 0.8 milliliter (mL) subcutaneous injection with vupanorsen 100 mg/mL solution
Receives: Drug: Vupanorsen
Vupanorsen 160 milligram (mg)ExperimentalParticipants will receive two, 0.8 mL subcutaneous injections with vupanorsen 100 mg/mL solution
Receives: Drug: Vupanorsen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area Under the Curve (AUC) From Time 0 to 24 Hours Post-dose (AUC24h) for Vupanorsen

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

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

  2. AUC From Time 0 to 48 Hours Post-dose (AUC48h) for Vupanorsen

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

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

  3. AUC From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for Vupanorsen

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

    Measured: 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

  4. Maximum Observed Concentration (Cmax)

    Maximum plasma concentration observed from data

    Measured: 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

  5. AUC From Time 0 Extrapolated to Infinite Time (AUCinf) for Vupanorsen

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

    Measured: 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

  6. Time for Cmax (Tmax) for Vupanorsen

    Time for Cmax (Tmax) for vupanorsen

    Measured: 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

  7. Terminal Elimination Half Life (t½) for Vupanorsen

    terminal elimination half life (t½) for vupanorsen

    Measured: 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

  8. Apparent Clearance (CL/F) for Vupanorsen

    Apparent clearance for vupanorsen

    Measured: 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

  9. Apparent Volume of Distribution (Vz/F) for Vupanorsen

    Apparent volume of distribution for vupanorsen

    Measured: 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

Secondary outcomes (14)

  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    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.

    Measured: Baseline through day 90

  2. Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)

    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.

    Measured: Baseline through day 90

  3. Number of Participants With Clinically Significant Vital Sign Values

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

    Measured: Baseline through day 90

  4. Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values

    Clinical significance of ECG data was assessed by the investigator.

    Measured: Baseline through day 90

  5. Percent Changes From Baseline in Angiopoietin-Like 3 (ANGPTL3)

    Percent changes from baseline in ANGPTL3 on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

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

  6. Percent Change From Baseline in Total Cholesterol

    Percentage changes from baseline in total cholesterol on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

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

  7. Percent Changs From Baseline in High-density Lipoprotein Cholesterol (HDL-C)

    Percentage changes from baseline in HDL-C on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

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

  8. Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)

    Percentage changes from baseline in LDL-C on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

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

  9. Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C)

    Percentage changes from baseline in VLDL-C on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

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

  10. Percent Change From Baseline in Triglyceride

    Percentage changes from baseline in triglyceride on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

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

  11. Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)

    Percentage changes from baseline in non-HDL on Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90

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

  12. Percent Change From Baseline in Apolipoprotein A-1 (ApoA-I)

    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.

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

  13. Percent Change From Baseline in Apolipoprotein B (ApoB) Total (Including ApoB-48, ApoB-100)

    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.

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

  14. Percent Change From Baseline in Apolipoprotein C-III (ApoC-III)

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jun 2021
  2. Study start17 Jun 2021
  3. Primary completion19 Oct 2021
  4. Study completion19 Oct 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04916795
Sponsor's protocol ID
C4491004
Status last verified
Aug 2023
First submitted
1 Jun 2021
Last updated
12 Mar 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Publications

  • Wu X, Yu J, Ge B, Wang J, Han X, Zhang C, Mao X, Kalluru H, Bramson C, Terra SG, Liu J. A Randomized, Open-Label, Phase I, Single-Dose Study of Antisense Oligonucleotide, Vupanorsen, in Chinese Adults with Elevated Triglycerides. Drugs R D. 2024 Jun;24(2):253-262. doi: 10.1007/s40268-024-00467-5. Epub 2024 Jul 1.

    PubMed 38949758

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vupanorsen in people with Healthy, run by Pfizer at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Curve (AUC) From Time 0 to 24 Hours Post-dose (AUC24h) for Vupanorsen (time frame: 0 hour (predose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on day 1). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04916795, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in