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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04916795
• Other study ID #: C4491004
• Status: Completed
• Phase: Phase 1
• Start date: June 17, 2021
• Est. completion date: October 19, 2021

Study information

• Verified date: August 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 19, 2021
• Est. primary completion date: October 19, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. 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.

2. 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.

3. 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).

4. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

5. BMI of 17.5 to 35.0 kg/m2; and a total body weight >50 kg (110 lb).

6. 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 (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

2. 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.

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. 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.

5. 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).

6. A positive urine drug test.

7. 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.

8. 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.

9. 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.

10. 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).

11. Blood donation (excluding plasma donations) of approximately 400 mL or more within 60 days prior to dosing.

12. History of sensitivity to heparin or heparin-induced thrombocytopenia.

13. History of substance abuse within 12 months of the screening visit.

14. Pregnant females; breastfeeding females.

15. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.

16. 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.

Related Conditions & MeSH terms

• Healthy

Intervention

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

Locations

Country	Name	City	State
China	Huashan Hospital,Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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.	Baseline through day 90
Secondary	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.	Baseline through day 90
Secondary	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.	Baseline through day 90
Secondary	Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values	Clinical significance of ECG data was assessed by the investigator.	Baseline through day 90
Secondary	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	Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Secondary	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	Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Secondary	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	Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Secondary	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	Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Secondary	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	Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Secondary	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	Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Secondary	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	Day 1, Day 2, Day 3, Day 8, Day 15, Day 30, Day 60 and Day 90
Secondary	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.	Day 1, Day 15, Day 60, and Day 90
Secondary	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.	Day 1, Day 15, Day 60, and Day 90
Secondary	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.	Day 1, Day 15, Day 60, and Day 90

External Links

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