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

• ClinicalTrials.gov Identifier: NCT04459767
• Recruitment Status: Completed
• First Posted: July 7, 2020
• Last Update Posted: December 22, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: July 1, 2020
• First Posted Date: July 7, 2020
• Last Update Posted Date: December 22, 2020
• Actual Study Start Date: August 6, 2020
• Actual Primary Completion Date: December 15, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 1, 2020)

• Incidence of treatment related adverse events [ Time Frame: Day 0-90 ]
• Incidence of abnormal and clinically relevant changes in electrocardiogram [ Time Frame: Day 0-90 ]
• Incidence and magnitude of abnormal laboratory findings [ Time Frame: Day 0-90 ]
• Incidence of abnormal and clinically relevant changes in pulse rate [ Time Frame: Day 0-90 ]
• Incidence of abnormal and clinically relevant changes in supine blood pressure [ Time Frame: Day 0-90 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 1, 2020)

• Maximum observed plasma concentration (Cmax) [ Time Frame: Day 0-90 ]
• Time to reach maximum observed plasma concentration (Tmax) [ Time Frame: Day 0-90 ]
• Area under the plasma concentration-time profile from time zero to 24 hours post-dose (AUC24h) [ Time Frame: Day 0-90 ]
• Area under the plasma concentration-time profile from time zero to 48 hours post-dose (AUC48h) [ Time Frame: Day 0-90 ]
• Area under the plasma concentration-time profile from time zero to the last measurable concentration (AUClast) [ Time Frame: Day 0-90 ]
• Area under the plasma concentration-time profile from time zero to infinity (AUCinf) [ Time Frame: Day 0-90 ]
• Terminal elimination half life (t1/2) [ Time Frame: Day 0-90 ]
• Apparent volume of distribution (Vz/F) [ Time Frame: Day 0-90 ]
• Apparent clearance (CL/F) [ Time Frame: Day 0-90 ]
• Percentage changes from baseline in serum angiopoietin-like protein 3 [ Time Frame: Day 0-90 ]
• Percentage changes from baseline in total cholesterol [ Time Frame: Day 0-90 ]
• Percentage changes from baseline in low density lipoprotein cholesterol [ Time Frame: Day 0-90 ]
• Percentage changes from baseline in non-high-density lipoprotein cholesterol [ Time Frame: Day 0-90 ]
• Percentage changes from baseline in very low density lipoprotein cholesterol [ Time Frame: Day 0-90 ]
• Percentage changes from baseline in triglyceride [ Time Frame: Day 0-90 ]
• Percentage changes from baseline in apolipoprotein A-1 [ Time Frame: Day 0-90 ]
• Percentage changes from baseline in apolipoprotein B total [ Time Frame: Day 0-90 ]
• Percentage changes from baseline in apolipoprotein C-III [ Time Frame: Day 0-90 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Investigation Of Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Single Doses Of Vupanorsen In Japanese Healthy Adult Participants With Elevated Triglycerides
• Official Title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, THIRD-PARTY OPEN, PLACEBO-CONTROLLED, SINGLE ASCENDING DOSE STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF-07285557 (VUPANORSEN) ADMINISTERED SUBCUTANEOUSLY IN JAPANESE HEALTHY ADULTS WITH ELEVATED TRIGLYCERIDES
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: Healthy

Intervention

• Drug: Vupanorsen
  80 mg subcutaneous injection
• Drug: Placebo
  Subcutaneous injection

Study Arms

• Experimental: Vupanorsen 80 milligram (mg)
  Participants will receive one, 0.8 milliliter (mL) subcutaneous injection with vupanorsen 100 mg/mL solution
  Intervention: Drug: Vupanorsen
• Experimental: Vupanorsen 160 mg
  Participants will receive two, 0.8 mL subcutaneous injections with vupanorsen 100 mg/mL solution
  Intervention: Drug: Vupanorsen
• Placebo Comparator: Placebo

  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.

  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 1, 2020): 12
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 15, 2020
• Actual Primary Completion Date: December 15, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male and female participants must be 20 to 65 years of age, inclusive, at the time of signing the ICD.
2. Participants must have four Japanese grandparents born in Japan.
3. 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.
4. Fasting TG >= 90 mg/dL at Screening
5. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
6. BMI of 17.5 to 35.0 kg/m2; and a total body weight >50 kg (110 lb)
7. 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.

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
2. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb.
3. 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.
4. History of allergic or anaphylactic reaction.
5. 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.
6. 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).
7. A positive urine drug test.
8. 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.
9. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.

10. 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.
11. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening.
12. 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.
13. History of sensitivity to heparin or heparin induced thrombocytopenia.
14. History of substance abuse within 12 months of the screening visit.
15. Pregnant females; breastfeeding females.
16. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
17. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT04459767
• Other Study ID Numbers: C4491006
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: 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.

• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: December 2020