Clinical trial NCT01232413: A Study of the Effect of ASP1941 on Cardiac Repolarization in Healthy Subjects
Official title: A Phase 1, Randomized, Double-Blind, Placebo- and Active-Controlled Crossover Study to Evaluate the Effect of Repeat Oral Doses of ASP1941 on Cardiac Repolarization in Healthy Male and Female Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Cardiac Repolarization
Keywords: Thorough QT (TQT)
ASP1941
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2010-11-02
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: The objective of this study is to evaluate the effect of repeat oral dosing of ASP1941 on electrocardiogram (ECG) measurements.

Detailed description: Subjects will be randomized in four treatment sequences of twenty subjects each. Subjects in each treatment sequence will participate in a total of four treatment periods (A, B, C, and D) separated by washout periods of at least 7 days from completion of the prior period (Day 8) through clinical check-in (Day -1) of the next study period.

For Period 1, subjects will be admitted to the clinical research unit on Day -2. For each subsequent study period, subjects will be admitted to the clinical research unit on Day -1. Subjects will be discharged from the unit after completing procedures on Day 8 of each period. Subjects will receive a follow-up telephone call 7-10 days after their last clinic day (Period 4\\Early Discontinuation \[ED\]).

Eligibility criteria: Inclusion Criteria:

* The subject weighs at least 45 kg, and has a body mass index (BMI) of 18 to 32 kg/m2
* If female, subject must be at least two years postmenopausal, surgically sterile or practicing effective birth control, and not pregnant or lactating
* The male or female subject agrees to practice highly effective birth control until 30 days post last study drug dose
* The subject is highly likely to comply with the protocol-defined procedures and complete the study

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 Long QT syndrome (suggested by sudden death due to cardiac causes at a young age of a close relative)
* The subject anticipates an inability to abstain from alcohol, or caffeine use, or from grapefruit and grapefruit juice from 72 hours prior to dosing and throughout the duration of the study
* The subject has used tobacco-containing products and nicotine or nicotine-containing products within past six months
* The subject is unable to tolerate a controlled, quiet study conduct environment, including avoidance during specified times (e.g., prior to and in ECG extraction windows) of music, TV, movies, games and activities that may cause excitement, emotional tension or arousal
* The subject is unwilling to comply with study rules, including attempting to void at specified times (e.g., prior to ECG extraction windows), remaining quiet, awake, undistracted, motionless and supine during specified times, and avoiding vigorous exercise as directed
* The subject is unable to tolerate study-specific diet
* The subject has a history or evidence of any clinically significant cardiovascular, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy (excluding non-melanoma skin cancer)
* The subject has a history of clinically significant allergic conditions or anaphylactic reactions
* The subject has any condition possibly affecting drug absorption
* The subject has a 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
* The subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous)infection within 1 week prior to clinic check in for any treatment period
* The subject is known positive for human immunodeficiency virus (HIV) antibody
* The subject has a positive test for hepatitis C antibody, or positive for hepatitis B antigen (HBsAg)
* The subject has used prescription or non-prescription drugs within 14 days or 5-half lives (whichever is longer) or complementary and alternative medicines (CAM) within 28 days prior to Day -2 of Period 1 (excluding oral contraceptives, hormone replacement therapy \[HRT\], and acetaminophen)
* The subject has received an experimental agent within 30 days or 10 half-lives, whichever is longer, prior to study drug administration
* The subject is participating in another clinical trial or has participated in another dose group of the current trial
* The subject has had any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission

Primary outcomes:
measure: QTcF evaluated through electrocardiogram analysis (ECG)
timeFrame: Days -1, 1 and 7 (period 1) and Days 1 and 7 (period 2-4)
Secondary outcomes:
measure: Evaluation of Electrocardiogram (ECG)
timeFrame: Days -1, 1 and 7 (period 1) and Days 1 and 7 (period 2-4)
measure: QTcI evaluated through electrocardiogram analysis
timeFrame: Days -1, 1 and 7 (period 1) and Days 1 and 7 (period 2-4)
measure: QTcB evaluated through electrocardiogram analysis (ECG)
timeFrame: Days -1, 1 and 7 (period 1) and Days 1 and 7 (period 2-4)
Other outcomes:
Locations:
city: West Bend
country: United States
state: Wisconsin
Study officials:
affiliation: Astellas Pharma Global Development
name: Use Central Contact
role: STUDY_DIRECTOR
References:
citation: Zhang W, Smulders R, Abeyratne A, Dietz A, Krauwinkel W, Kadokura T, Keirns J. Ipragliflozin does not prolong QTc interval in healthy male and female subjects: a phase I study. Clin Ther. 2013 Aug;35(8):1150-1161.e3. doi: 10.1016/j.clinthera.2013.06.009. Epub 2013 Aug 2.