Investigation Of Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Single Doses Of Vupanorsen In Japanese Healthy Adult Participants With Elevated Triglycerides
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Vupanorsen 80 milligram (mg) Participants will receive one, 0.8 milliliter (mL) subcutaneous injection with vupanorsen 100 mg/mL solution |
Drug: Vupanorsen
80 mg subcutaneous injection
|
| Experimental: Vupanorsen 160 mg Participants will receive two, 0.8 mL subcutaneous injections with vupanorsen 100 mg/mL solution |
Drug: Vupanorsen
80 mg subcutaneous injection
|
| 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. |
Drug: Placebo
Subcutaneous injection
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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]
- Area under the plasma concentration-time profile from time zero to infinity (AUCinf) [Day 0-90]
- Terminal elimination half life (t1/2) [Day 0-90]
- Apparent volume of distribution (Vz/F) [Day 0-90]
- Apparent clearance (CL/F) [Day 0-90]
- Percentage changes from baseline in serum angiopoietin-like protein 3 [Day 0-90]
- Percentage changes from baseline in total cholesterol [Day 0-90]
- Percentage changes from baseline in low density lipoprotein cholesterol [Day 0-90]
- Percentage changes from baseline in non-high-density lipoprotein cholesterol [Day 0-90]
- Percentage changes from baseline in very low density lipoprotein cholesterol [Day 0-90]
- Percentage changes from baseline in triglyceride [Day 0-90]
- Percentage changes from baseline in apolipoprotein A-1 [Day 0-90]
- Percentage changes from baseline in apolipoprotein B total [Day 0-90]
- Percentage changes from baseline in apolipoprotein C-III [Day 0-90]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male and female participants must be 20 to 65 years of age, inclusive, at the time of signing the ICD.
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Participants must have four Japanese grandparents born in Japan.
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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.
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Fasting TG >= 90 mg/dL at Screening
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Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
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BMI of 17.5 to 35.0 kg/m2; and a total body weight >50 kg (110 lb)
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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:
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Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
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History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb.
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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.
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History of allergic or anaphylactic reaction.
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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.
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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).
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A positive urine drug test.
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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.
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Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
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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:
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AST or ALT level >=1.25 × ULN;
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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.
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History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening.
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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.
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History of sensitivity to heparin or heparin induced thrombocytopenia.
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History of substance abuse within 12 months of the screening visit.
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Pregnant females; breastfeeding females.
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Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | P-one Clinic | Hachioji-shi | Tokyo | Japan | 192-0071 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- C4491006