CiPA Phase 1 ECG Biomarker Validation Study

Completed · Phase 1 · Has a placebo group

Conditions studied: Drug-induced QT Prolongation, Pharmacokinetics, Pharmacodynamics

In brief

This study will assess whether exposure response analysis of the electrocardiographic QTc and J-Tpeakc intervals in Phase 1 clinical pharmacology studies can be used to confirm that drugs that predominantly block the potassium channel encoded by the human ether-à-go-go-related gene (hERG) with approximately equipotent late sodium and/or calcium block ("balanced ion channel" drugs) do not cause J-Tpeakc prolongation and that drugs that predominantly block hERG without late sodium or L-type calcium current block ("predominant hERG" drugs) cause QTc prolongation.

Key facts

Study ID

NCT03070470

Run by

Food and Drug Administration (FDA)

People needed

60

Starts

2017-03-14

Expected to finish

2017-06-26

Last updated by the study team

2020-01-18

Who can join

Age: 18 and older, up to 50. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• Subject signs an institutional review board (IRB) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] authorization) before any study related procedures are performed.
• Subject is a healthy man or woman, 18 to 50 years of age, inclusive, who weighs at least 50 kg (110 pounds) and has a body mass index of 18 to 30 kg/m2, inclusive, at Screening.
• Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12 lead ECG results, and physical examination findings at Screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
• Female subjects will be at least 2 years postmenopausal, surgically sterile, or practicing 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique).
• Female subjects must not be pregnant or lactating before enrollment in the study.
• Male or female subjects must agree to practice 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from Screening until 30 days after the last dose of study drug.
• Subject is highly likely (as determined by the investigator) to comply with the protocol defined procedures and to complete the study.

You may not qualify if…

• Subject has a safety 12 lead ECG result at Screening or Check in with evidence of any of the following abnormalities:
• QTc using Fridericia correction (QTcF) >430 msec
• PR interval >220 msec or <120 msec
• QRS duration >110 msec
• Second- or third-degree atrioventricular block
• Complete left or right bundle branch block or incomplete right bundle branch block
• Heart rate <50 or >90 beats per minute
• Pathological Q-waves (defined as Q wave >40 msec)
• Ventricular pre-excitation
• Subject has more than 12 ectopic beats during the 3 hour Holter ECG at Screening.
• Subject has a history of unexplained syncope, structural heart disease, long QT syndrome, heart failure, myocardial infarction, angina, unexplained cardiac arrhythmia, torsade de pointes, ventricular tachycardia, or placement of a pacemaker or implantable defibrillator. Subjects will also be excluded if there is a family history of long QT syndrome (genetically proven or suggested by sudden death of a close relative due to cardiac causes at a young age) or Brugada syndrome.
• Subject has a history or current evidence of any clinically significant (as determined by the investigator) cardiovascular, dermatologic, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, neurologic, psychiatric, pulmonary, renal, urologic, and/or other major disease or malignancy (excluding nonmelanoma skin cancer). The investigator may allow exceptions to these criteria (e.g., cholecystectomy, childhood asthma) following discussion with the medical monitor.
• Subject has a history of thoracic surgery.
• Subject has any condition possibly affecting study drug absorption (e.g., gastrectomy, Crohn's disease, irritable bowel syndrome).
• Subject has a skin condition likely to compromise ECG electrode placement.
• Subject is a female with breast implants.
• Subject's laboratory test results at Screening or Check in are outside the reference ranges provided by the clinical laboratory and considered clinically significant (as determined and documented by the investigator or designee).
• Subject's laboratory test results at Screening or Check in indicate hypokalemia, hypocalcemia, or hypomagnesemia according to lower limits of the reference ranges provided by the clinical laboratory.
• Subject's laboratory test results at Screening or Check in are >2 × the upper limit of normal (ULN) for alanine aminotransferase or aspartate aminotransferase, >1.5 × ULN for bilirubin, or >1.5 × ULN for creatinine.
• Subject has a positive test result at Screening for human immunodeficiency virus I or II antibody, hepatitis C virus antibodies, or hepatitis B surface antigen.
• Subject has a mean systolic blood pressure <100 or >140 mmHg or a mean diastolic blood pressure <50 or >90 mmHg at either Screening or Check in. Blood pressure will be measured in triplicate after the subject has been resting in a supine position for a minimum of 5 minutes.
• Subject has a known hypersensitivity to any of the study drugs or related compounds.
• Subject has consumed alcohol, xanthine containing products (e.g., tea, coffee, chocolate, cola), caffeine, grapefruit, or grapefruit juice within 48 hours before dosing or anticipates an inability to abstain from these products throughout the duration of the study.
• Subject has used nicotine containing products (e.g., cigarettes, cigars, chewing tobacco, snuff) within 6 weeks before Screening (self reported).
• Subject is unable to tolerate a controlled, quiet, study conduct environment, including avoidance of music, television, movies, games, and activities that may cause excitement, emotional tension, or arousal during the prespecified time points (e.g., before and during ECG extraction windows).

Where it is running

• Spaulding Clinical Research — West Bend, Wisconsin, United States

Full record on ClinicalTrials.gov

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