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

NCT04916795 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C4491004
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (9)

• 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

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

• 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

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

• 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)

  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 Observed Concentration (Cmax)

  Maximum plasma concentration observed from data

  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

• 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

  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

  Time for Cmax (Tmax) for vupanorsen

  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

  terminal elimination half life (t½) for vupanorsen

  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 (CL/F) for Vupanorsen

  Apparent clearance for vupanorsen

  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 (Vz/F) for Vupanorsen

  Apparent volume of distribution for vupanorsen

  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)

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

  Baseline through day 90

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

  Baseline through day 90

• Number of Participants With Clinically Significant Vital Sign Values

  Baseline through day 90

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

  Baseline through day 90

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

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

Study Arms (2)

Vupanorsen 80 milligram (mg)

EXPERIMENTAL

Participants will receive one, 0.8 milliliter (mL) subcutaneous injection with vupanorsen 100 mg/mL solution

Drug: Vupanorsen

Vupanorsen 160 milligram (mg)

EXPERIMENTAL

Participants will receive two, 0.8 mL subcutaneous injections with vupanorsen 100 mg/mL solution

Drug: Vupanorsen

Interventions

Vupanorsen DRUG

80 mg subcutaneous injection

Vupanorsen 80 milligram (mg)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Huashan Hospital,Fudan University

Shanghai, Shanghai Municipality, 201107, China

Location

Related Publications (1)

• 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.

  PMID: 38949758 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

vupanorsen

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2021
• First Posted: June 8, 2021
• Study Start: June 17, 2021
• Primary Completion: October 19, 2021
• Study Completion: October 19, 2021
• Last Updated: March 12, 2024
• Results First Posted: March 12, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)