Trial registered on ANZCTR


Trial ID
ACTRN12610000292077
Ethics application status
Approved
Date submitted
1/04/2010
Date registered
13/04/2010
Date last updated
11/07/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of SYR-472 on Cardiac Function in Healthy Adults
Scientific title
A Randomized, Double-blind, Placebo- and Positive-controlled, Parallel Study to Evaluate the Effect of SYR-472 on the QT/QTc Interval in Healthy Adult Male and Female Subjects
Secondary ID [1] 1576 0
Nil
Universal Trial Number (UTN)
U1111-1114-4448
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Effects on Cardiac QT/QTc Interval 256984 0
Condition category
Condition code
Metabolic and Endocrine 257135 257135 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention 1: SYR-472 200 mg, tablets, orally, one day only.

Intervention 2: SYR-472 800 mg, tablets, orally, one day only.
Intervention code [1] 256159 0
Treatment: drugs
Comparator / control treatment
Intervention 3: Moxifloxacin 400 mg (positive control), tablets, orally, one day only.


Intervention 4: Placebo-matching tablets (microcrystalline cellulose 202 mg), orally, one day only
Control group
Placebo

Outcomes
Primary outcome [1] 258031 0
The largest difference in time-matched baseline-adjusted least squares means in QT interval corrected for heart rate using the Fridericia method (QTcF) between SYR-472 and placebo at post-treatment electrocardiogram collection times.
Timepoint [1] 258031 0
Baseline and Final Collection Date (Up to 23.5 hours post dosing).
Secondary outcome [1] 263592 0
The difference in time-matched baseline-adjusted least squares means in QTcF and QT interval corrected for heart rate using the study-specific method (QTcss) between SYR-472 and placebo at post-treatment electrocardiogram collection times.
Timepoint [1] 263592 0
Baseline and Final Collection Date (Up to 23.5 hours post dosing).
Secondary outcome [2] 263593 0
Categorical evaluation of the number and percentage of subjects with time-matched increases in QTcF and QTcss intervals of >30 ms and >60 ms from baseline, and the number and percentage of subjects with QTcF and QTcss intervals of >450 ms, >480 ms and >500 ms.
Timepoint [2] 263593 0
Baseline and Final Collection Date (Up to 23.5 hours post dosing).
Secondary outcome [3] 263594 0
Safety assessments including adverse events (potential adverse events are not yet known), safety electrocardiograms, vital signs, weight and clinical laboratory values (hematology and serum chemistry).
Timepoint [3] 263594 0
Baseline and Final Visit (Up to 8 days post final dosing).

Eligibility
Key inclusion criteria
*Subjects must be healthy volunteers
*Subjects must weigh at least 50 kg and have a body mass index greater than or equal to 18.5 kg/m2 and less than 30 kg/m2
*Subjects must be in good health in the judgment of the investigator.
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* Subjects will not be enrolled if the screening electrocardiogram has abnormalities including second- or third-degree atrioventricular block, or one or more of the following: QTcF >450 milliseconds (ms), QRS >120 ms, PR interval of >240 ms or any other rhythm than sinus rhythm, which is interpreted by the investigator to be clinically significant.
* History of additional risk factors for Torsade de pointes (e.g., long QT syndrome)
* Has a heart rate at rest of <50 bpm or >100 bpm
*Uses prescription medications within 4 weeks (28 days) prior to the start of the investigational drug administration
*Use of over-the-counter medications within 1 week (7 days) prior to the start of the investigational drug administration.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Approximately 260 healthy subjects will be randomized in this study to receive one of the following 4 treatments (65 subjects per treatment group): SYR-472 200 mg, SYR-472 800 mg, placebo or moxifloxacin. This study is double-blind except for the moxifloxacin positive control group included to establish assay sensitivity in the subjects enrolled in this study.

Study drug will be prescribed in numerical order by using a randomization-table (schedule) generated by computer and prepared by sex, and will be provided to the investigator in advance. All randomization information will be stored in a secured area accessible only to authorized personnel. Allocation concealed.

If the subject has satisfied all the inclusion criteria and none of the exclusion criteria for randomization, the subject will be randomized. If the investigator judges that there are some problems with the eligibility of a subject at check-in, the subject may be replaced by a reserve subject. In such cases, the reserve subject will receive the investigational drug that was allocated to the original subject.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subjects will be assigned in the order in which they are enrolled into the study and receive the next available randomization sequence number allocated to the study site and gender. Subjects will be stratified by gender.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 256660 0
Commercial sector/Industry
Name [1] 256660 0
Takeda Pharmaceutical Company Limited
Address [1] 256660 0
1-1 Doshomachi 4-chome, Chuo-ku, Osaka 540-8645
Country [1] 256660 0
Japan
Primary sponsor type
Commercial sector/Industry
Name
Takeda Pharmaceutical Company Limited
Address
1-1 Doshomachi 4-chome, Chuo-ku, Osaka 540-8645
Country
Japan
Secondary sponsor category [1] 255948 0
None
Name [1] 255948 0
Address [1] 255948 0
Country [1] 255948 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258682 0
The Alfred Human Research Ethics Committee
Ethics committee address [1] 258682 0
The Alfred Hospital
55 Commercial Road
Melbourne, Victoria 3004
Ethics committee country [1] 258682 0
Australia
Date submitted for ethics approval [1] 258682 0
20/04/2010
Approval date [1] 258682 0
Ethics approval number [1] 258682 0
34/10

Summary
Brief summary
Type 2 diabetes mellitus is a complex metabolic disorder characterized by abnormal insulin secretion and an abnormal glucose balance. The primary risk factor for developing type 2 diabetes mellitus is obesity, which can result in insulin resistance in the body. Insulin resistance is characterized by an impaired response to the physiologic effects of insulin, and leads to decreased cellular glucose uptake, increased hepatic gluconeogenesis and a compensatory increase in insulin secretion that contributes to beta-cell exhaustion.

SYR-472 is being developed by Takeda Pharmaceutical Company Ltd. as an adjunct to diet and exercise to treat patients with type 2 diabetes mellitus.

Medicinal products that prolong cardiac repolarization have been associated with a specific, potentially fatal polymorphic ventricular tachycardia called torsade de pointes.

Although no evidence of cardiovascular effects have been noted in non-clinical studies of SYR-472 nor treatment-related trends revealed in phase 1 studies of SYR-472, this study is being conducted to investigate the effect of SYR-472 on electrocardiography in healthy adults, in compliance with the International Conference of Harmonization Tripartite Guideline: The clinical evaluation of QT/QTc (QT interval corrected for heart rate ) interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs (ICH E14).
Trial website
http://www.nucleusnetwork.com.au/page.aspx?54
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30952 0
Address 30952 0
Country 30952 0
Phone 30952 0
Fax 30952 0
Email 30952 0
Contact person for public queries
Name 14199 0
Project Manager
Address 14199 0
Nucleus Network Limited
5th Floor Burnet Tower, AMREP Precinct, 89 Commercial Road Melbourne, Victoria 3004
Country 14199 0
Australia
Phone 14199 0
+61-3-9076-9017
Fax 14199 0
+61-3-9076-8911
Email 14199 0
medicalinformation@tpna.com
Contact person for scientific queries
Name 5127 0
Primary Investigator
Address 5127 0
Nucleus Network Limited
5th Floor Burnet Tower, AMREP Precinct, 89 Commercial Road, Melbourne, Victoria 3004
Country 5127 0
Australia
Phone 5127 0
+61-3-9076-8960
Fax 5127 0
+61-3-9076-8940
Email 5127 0
medicalinformation@tpna.com