Bepirovirsen's Effect on Heart Function

Recruiting in Palo Alto (17 mi)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: GlaxoSmithKline

Must not be taking: Herbal medications, Creatine supplements

Disqualifiers: Cardiovascular, Respiratory, Hepatic, others

Trial Summary

What is the purpose of this trial?

This study will evaluate the effect of a single dose of bepirovirsen on the QT interval corrected by Fridericia's formula (QTcF) as compared to placebo. The data generated will be used to model the relationship between bepirovirsen concentration and QTcF.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any over-the-counter or prescription medications, including herbal medications, at least 7 days or 5 half-lives (whichever is longer) before the study dosing.

How does the drug Bepirovirsen differ from other treatments for heart function?

Bepirovirsen is unique because it is primarily known for its use in treating hepatitis B, and its application to heart function is novel. Unlike typical heart medications, Bepirovirsen's mechanism of action and effects on heart function are not well-documented, making it a potentially innovative approach in this area.

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Eligibility Criteria

This trial is for healthy volunteers who want to help test the effects of a drug called Bepirovirsen on heart function. Participants should not have any current health issues, especially related to hepatitis or heart conditions.

Inclusion Criteria

Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, Electrocardiogram (ECGs) and vital signs

I am a male participant with no need for birth control measures.

I weigh at least 50 kg and my BMI is between 19 and 32.

Exclusion Criteria

I do not have major health issues that could affect how my body handles medication.

Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention

Positive Human Immunodeficiency Virus antibody test

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of bepirovirsen or placebo to evaluate its effect on cardiac conduction

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The study is testing how a single dose of Bepirovirsen affects the electrical activity of the heart (QT interval) compared to a placebo. The results will help understand if there's any risk of abnormal heart rhythms.

Group I: Participants receiving Bepirovirsen Experimental Treatment 1 Intervention

Group II: Participants receiving Placebo Placebo Group 1 Intervention

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

GSK Investigational Site Austin, TX

Who Is Running the Clinical Trial?

GlaxoSmithKline Lead Sponsor

PPD Industry Sponsor

Laboratory Corporation of America Industry Sponsor

PPD DEVELOPMENT, LP Industry Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Short- and long-term treatment of dilutional hyponatraemia with satavaptan, a selective arginine vasopressin V2-receptor antagonist: the DILIPO study. [2014] Arginine vasopressin (AVP) V(2) receptor antagonism is a new approach to the management of hyponatraemia in congestive heart failure (CHF). The aim of this study was to investigate the efficacy and safety of satavaptan, an oral AVP V(2)-receptor antagonist, in patients with dilutional hyponatraemia.

2. United States pubmed.ncbi.nlm.nih.gov

Reflex parasympathetic coronary vasodilation elicited from cardiac receptors in the dog. [2019] Veratrum alkaloids injected into the coronary circulation stimulate myocardial receptors to produce reflex bradycardia and arterial hypotension (the Bezold-Jarisch reflex). This study investigated the hypothesis that parasympathetic coronary vasodilation occurs as part of the Bezold-Jarisch reflex. Blood flow in the circumflex coronary artery was measured in chloralose-anesthetized, closed-chest dogs with a newly developed cannula-tip flow transducer. Alpha-receptor blockade with Dibozane (2 mg/kg) was used to prevent peripheral vasodilation, and beta-receptor blockade with propranolol (1 mg/kg) was used to prevent adrenergic cardiac effects. Electrical pacing was used to maintain a constant heart rate. Under these conditions, veratridine injected into the anterior descending coronary artery but not into the circumflex coronary artery produced a 63% increase in circumflex coronary blood flow and an 88% increase in diastolic coronary conductance. The effect was abolished when the reflex arc was interrupted by either vagotomy or atropine administration. It is concluded that a cardiocoronary reflex parasympathetic coronary vasodilation can be elicited by stimulating cardiac receptors with veratridine.

3. England pubmed.ncbi.nlm.nih.gov

The potential role for lixivaptan in heart failure and in hyponatremia. [2014] Hypervolemia and hyponatremia are common features in heart failure and have been associated with increased morbidity and mortality. Stimulation of arginine vasopressin (AVP) plays an important role in the development of both hypervolemia and hyponatremia. Lixivaptan is a selective vasopressin type 2 (V(2)) receptor antagonist that has been demonstrated to have the ability to induce aquaresis, the electrolyte sparing excretion of water, resulting in fluid removal as well as correction of hyponatremia.

4. United States pubmed.ncbi.nlm.nih.gov

Effects of a vasopressin antagonist with combined antipressor and antiantidiuretic activities in rats with left ventricular dysfunction. [2019] These experiments assessed the hemodynamic and aquaretic effects of an arginine vasopressin (AVP) antagonist with dual V1V2-receptor inhibiting properties in rats with congestive heart failure resulting from ischemic cardiomyopathy. The compound d(CH2)5-D-Tyr(Et)VAVP was used in these studies. Rats with limited or extensive myocardial infarcts (i.e., with less than 50% or greater than 66% necrosis of the left ventricular wall, respectively, induced by left coronary ligation) and sham-operated controls received the AVP antagonist (100 micrograms/kg i.v.) 4 weeks later. This agent produced an 18% increase in cardiac output (p less than 0.05) and 13% decrease in systemic vascular resistance in the severely damaged rats, both changes being significantly different from those seen in the normal controls or the rats with limited infarcts. All animals exhibited increases in urinary output of 4-10-fold over baseline. We conclude that the hemodynamic and renal effects of this agent are beneficial in animals with left ventricular dysfunction.

5. England pubmed.ncbi.nlm.nih.gov

DDAVP (1-desamino-8-D-arginine vasopressin): an antagonist of the pressor action of endogenous vasopressin? [2014] The pressor effect of arginine vasopressin (AVP) is thought to be mediated by a calcium-dependent mechanism (V1-receptor) whereas its antidiuretic effect depends on c-AMP (V2-receptor). 1-Desamino-8-D-arginine-vasopressin (DDAVP) is possibly an antagonist on the V1-receptor and may therefore be used for assessing the role of endogenous AVP in blood pressure regulation. This possibility was tested using the following models: aggregation of human platelets, renin secretion by rabbit kidney slices, and blood pressure and renin responses in normal human subjects (n = 11) and patients with autonomic insufficiency (n = 4). AVP 10(-10)-10(-7) mol/l caused dose-dependent platelet aggregation and inhibition of renin secretion. These effects were absent in a calcium free medium or in the presence of the calcium antagonist verapamil 5 X 10(-5) mol/l. DDAVP up to 10(-5) mol/l had no effect but shifted the dose-response curves of AVP to the right. AVP infusion into normal subjects is known to lower heart rate and plasma renin with little change in blood pressure. DDAVP 400 ng/kg in 10 min caused no change in systolic pressure but diastolic pressure was lowered by 14 +/- 2 mmHg (mean +/- s.e.m.). Heart rate rose by 24 +/- 2 beats/min and renin rose from 21 +/- 4 to 57 +/- 9 muu/ml (P less than 0.01). In the patients with autonomic insufficiency both systolic and diastolic pressures fell by 20-50 mmHg after DDAVP 200 ng/kg without any change in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)