Repeat Dose Tolerance Study of Regadenoson in Healthy Subjects

A Phase 1, Randomized, Double-blind, Dose Escalation, Parallel Group, Placebo-controlled, Repeat Dose Tolerance Study of Regadenoson in Healthy Subjects

This study is to determine the safety, tolerability, and pharmacokinetics of two or three repeat intravenous (IV) bolus doses of regadenoson administered 10 minutes apart in healthy supine subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: Regadenoson

Detailed Description

All subjects will receive up to 3 doses of study drug on day 1 after fasting from all food and drink (except water) for at least 8 hours. Subjects will remain in the clinic for 2 days.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Parexel Early Phase Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The subject has a body weight of at least 45 kg and a body mass index of 18 to 32 kg/m2, inclusive.
• QTcF must be 430 msec or less for males and 450 msec or less for females. If the mean QTcF exceeds 430 msec for males or 450 msec for females, 1 additional triplicate measurement may be taken. If this triplicate measurement also gives an abnormal QTcF result, the subject should be excluded.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (TBil) must not be above the normal range. If the Screening test result for AST, ALT, or TBil is > 1 x ULN, but < 1.5 x ULN the assessment may be repeated once during the screening period and on day -1. If the repeat assessment is above the ULN, the subject is not eligible. If the AST, ALT, or TBil test result at Screening is > 1.5 x ULN, it cannot be repeated, and the subject is not eligible.
• Female subject is of non-childbearing potential or if of childbearing potential must use highly effective birth control from Screening through 28 days after the end of the study. Females must not be breastfeeding or donate ova from Screening through 20 days after the end of the study.
• Male subject must be using highly effective contraception from Screening through 90 days after final study drug administration. Male subject must not donate sperm starting at Screening through 90 days after final study drug administration.

Exclusion Criteria:

• The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia or torsade de pointes, structural heart disease, or family history of either Short or Long QT syndrome (suggested by sudden death of a close relative at a young age due to possible or probable cardiac causes).
• The subject has a positive result for hepatitis B surface antigen, hepatitis C antibodies at Screening or is known to be positive for human immunodeficiency virus.
• The subject has a known or suspected allergy to regadenoson or any of the components of the trial products, or a history of multiple and/or severe allergies to drugs or foods, or a history of severe anaphylactic reactions.
• Subject has a history of smoking, regardless of frequency, tobacco type or method of intake, within 6 months prior to first dose of regadenoson.
• The subject has had treatment with any prescribed or non-prescribed drugs in the 2 weeks prior to Day 1, with the exception of occasional use of acetaminophen up to 2 g/day.
• The subject has participated in any interventional clinical study or has received any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to Screening.
• The subject has participated in a prior study with regadenoson.
• The subject has history of consuming more than 14 units of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism or drug/chemical/substance abuse within past 2 years prior to screening or the subject tests positive at screening or Day -1 for alcohol or drugs of abuse.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Regadenoson low dose; Administered over approximately 10 seconds followed by 2 repeat low doses at 10 minute intervals	Drug: Regadenoson; Intravenous (IV); Other Names: Lexiscan; CVT3146
Experimental: Regadenoson medium dose; Administered over approximately 10 seconds followed by 2 repeat medium doses at 10 minute intervals	Drug: Regadenoson; Intravenous (IV); Other Names: Lexiscan; CVT3146
Experimental: Regadenoson high dose; Administered over approximately 10 seconds followed by 1 repeat high dose at 10 minute intervals	Drug: Regadenoson; Intravenous (IV); Other Names: Lexiscan; CVT3146
Placebo Comparator: Placebo; Administered over approximately 10 seconds followed by 1 or 2 repeat doses at 10 minute intervals	Drug: Placebo; Intravenous (IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety assessed by vital signs	Pre-dose and up to 24 hours post dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety assessed by electrocardiogram (ECG), laboratory evaluations, and adverse events	Up to 72 hours after last dose of study drug

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.

Publications and helpful links

General Publications

• Townsend R, Desai A, Rammelsberg D, Kowalski D, Simmons N, Kitt TM. Safety and tolerability of intravenous regadenoson in healthy subjects: A randomized, repeat-dose, placebo-controlled study. J Nucl Cardiol. 2017 Feb;24(1):57-65. doi: 10.1007/s12350-015-0327-9. Epub 2015 Nov 25.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: August 6, 2013
• First Submitted That Met QC Criteria: August 6, 2013
• First Posted (Estimate): August 8, 2013

Study Record Updates

• Last Update Posted (Estimate): August 30, 2013
• Last Update Submitted That Met QC Criteria: August 28, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Regadenoson; CVT3146
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Purinergic Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine A2 Receptor Agonists; Regadenoson
• Other Study ID Numbers: 3606-CL-1005