Investigation Of Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Single Doses Of Vupanorsen In Japanese Healthy Adult Participants With Elevated Triglycerides

NCT04459767 | Completed Phase 1 FDA Drug

• 1 other identifier: C4491006
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, randomized, double blind, third party open (i.e., participant blind, investigator blind and sponsor open), placebo controlled, single ascending dose study to investigate the safety, tolerability, pharmacokinetic and pharmacodynamics of vupanorsen in Japanese healthy adult participants with elevated triglycerides.

Conditions

Healthy

Keywords

Triglycerides

Outcome Measures

Primary Outcomes (5)

• Incidence of treatment related adverse events

  Day 0-90

• Incidence of abnormal and clinically relevant changes in electrocardiogram

  Day 0-90

• Incidence and magnitude of abnormal laboratory findings

  Day 0-90

• Incidence of abnormal and clinically relevant changes in pulse rate

  Day 0-90

• Incidence of abnormal and clinically relevant changes in supine blood pressure

  Day 0-90

Secondary Outcomes (18)

• Maximum observed plasma concentration (Cmax)

  Day 0-90

• Time to reach maximum observed plasma concentration (Tmax)

  Day 0-90

• Area under the plasma concentration-time profile from time zero to 24 hours post-dose (AUC24h)

  Day 0-90

• Area under the plasma concentration-time profile from time zero to 48 hours post-dose (AUC48h)

  Day 0-90

• Area under the plasma concentration-time profile from time zero to the last measurable concentration (AUClast)

  Day 0-90

Study Arms (3)

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 mg

EXPERIMENTAL

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

Drug: Vupanorsen

Placebo

PLACEBO COMPARATOR

Participants in Cohort 1 (vupanorsen 80 mg) will receive one 0.8 mL subcutaneous injection with 0.9% sodium chloride in water. Participants in Cohort 2 (vupanorsen 160 mg) will receive two 0.8 mL subcutaneous injections with 0.9% sodium chloride in water.

Drug: Placebo

Interventions

Vupanorsen DRUG

80 mg subcutaneous injection

Vupanorsen 160 mg; Vupanorsen 80 milligram (mg)

Placebo DRUG

Subcutaneous injection

Placebo

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants must be 20 to 65 years of age, inclusive, at the time of signing the ICD.
• Participants must have four Japanese grandparents born in Japan.
• Male and female 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
• 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.
• History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb.
• 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.
• History of allergic or anaphylactic reaction.
• 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.
• 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.
• Blood donation (excluding plasma donations and platelet donations) of approximately 400 mL within 3 months or \>=200 mL within a month prior to dosing. Additionally, approximately \>=400 mL within 4 months for female participants.
• History of sensitivity to heparin or heparin induced thrombocytopenia.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

P-one Clinic

Hachioji-shi, Tokyo, 192-0071, Japan

Location

Related Publications (1)

• Fukuhara K, Furihata K, Matsuoka N, Itamura R, Ramos V, Hagi T, Kalluru H, Bramson C, Terra SG, Liu J. A multi-purpose Japanese phase I study in the global development of vupanorsen: Randomized, placebo-controlled, single-ascending dose study in adults. Clin Transl Sci. 2023 May;16(5):886-897. doi: 10.1111/cts.13498. Epub 2023 Mar 31.

  PMID: 37002654 DERIVED

Related Links

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

MeSH Terms

Interventions

vupanorsen

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2020
• First Posted: July 7, 2020
• Study Start: August 6, 2020
• Primary Completion: December 15, 2020
• Study Completion: December 15, 2020
• Last Updated: December 22, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)