Effect of Saroglitazar Magnesium on the QTc Interval in Healthy Volunteers
- Registration Number
- CTRI/2019/08/020638
- Lead Sponsor
- Zydus Discovery DMCC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
1)Provision of signed and dated written informed consent prior to any study-specific procedures being performed.
2)Willing and able to comply with the study procedures, restrictions, and requirements.
3)Body mass index of 19.0 to 25.0 kg/m2 (inclusive) with a body weight of 50 to 100 kg (inclusive).
4)Subjects must be non-smokers and must not drink alcohol (teetotal).
5)Subjects who, in the opinion of the Investigator, are healthy as determined by their pre-study medical history, physical examination, and 12-lead ECG, and clinical laboratory tests within the institutional normal range or judged as not clinically significant by the Investigator, including the following parameters: hematology, serum biochemistry, urinalysis, and serology.
6)Male subjects and female subjects of childbearing potential must practice highly effective contraception during the study and be willing and able to continue contraception for 90 days after their last administration of study treatment.
7)Systemic blood pressure with a systolic blood pressure of 100 to 140 mmHg and a diastolic blood pressure of 60 to 90 mmHg.
1)History of cardiovascular disease (eg, hypertension, arrhythmia, heart failure, long QT syndrome, or other conditions/diseases causing prolongation of the QT/QTc interval), in the opinion of the Investigator.
2)A prolongation of the QT interval corrected for HR using Fridericiaâ??s correction (QTcF) interval (eg, repeated demonstration of a QTcF interval >450 msec) before study treatment administration.
3. Any clinically important abnormalities in the ECG at screening, check-in (Day -1), or predose on Day 1. This includes subjects with any of the following:
a. PR interval >210 msec;
b. QRS >110 msec; or
c. HR <45 beats per minute (bpm) or >100 bpm.
4)A QRS and/or T-wave value that the Investigator judges to be unfavorable for consistently accurate QT measurements (eg, indistinct QRS onset, low amplitude T-wave, inverted or terminally-inverted T-wave, merged T/U-waves, indistinct T-wave offset, or prominent U-wave that affects QT measurement).
5)History of additional risk factors for Torsades de Pointes or the presence of a family history of short QT syndrome, long QT syndrome, sudden unexplained death at a young age (<=40 years), drowning or sudden infant death syndrome in a first degree relative (ie, biological parent, sibling, or child).
6)Use of medications in the 90 days before Day -1 of Period 1 that are known to prolong the QT/QTc interval.
7)Has used prescription drugs and other substances (eg, dietary or herbal supplements such as St Johnâ??s Wort) known to be either significant enzyme inducers or enzyme inhibitors within 4 weeks of Day 1 of Period 1, or use of grapefruit or similar substances (Seville oranges or marmalade, grapefruit juice, grapefruit hybrids, pomelos, exotic citrus fruits or fruit juices) within 7 days of Day 1 of Period 1.
8)Has used prescription or over-the-counter medication, excluding routine vitamins but including megadose vitamin therapy (intake of 20 to 600 times the recommended daily dose), within 7 days of Day 1 of Period 1, unless agreed as not clinically relevant by the Investigator and Sponsor.
9)Any history of malignant disease, including solid tumors, hematologic malignancies, and including any carcinoma in situ.
10)Clinically significant allergies, as determined by the Investigator.
11)History of any clinically significant endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major diseases, as determined by the Investigator.
12) History of unexplained syncopal or hypotensive episodes.
13)A positive cotinine test and positive breath test at screening or check-in (Day -1) of Period 1.
14)Surgery within 12 months prior to check-in (Day -1) of Period 1 (other than minor cosmetic surgery and minor dental surgery).
15)Subjects who have recent illness (eg, fever >38°C) within 7 days of check-in (Day -1) of Period 1.
16)Clinically significant abnormal hematology and serum biochemistry values, as determined by the Investigator or any of the following values at screening or check-in (Day -1) of Period 1:
a. Alanine aminotransferase, aspartate aminotransferase, or creatinine above their reference range.
b. Hemoglobin or platelets below their reference range.
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Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1)Title: QTcF change-from-baseline <br/ ><br>2)Description: Linear-mixed model will be used to assess the effect of saroglitazar magnesium on cardiac repolarization on Day 1 to evaluate whether saroglitazar magnesium prolongs the QTcF when orally administered to healthy volunteers <br/ ><br>Timepoint: Pre-dose (-1.0 hr) to 24 hours post dose
- Secondary Outcome Measures
Name Time Method Observed and change-from-baseline HR, PR, RR, QRS, and QT and ECG morphological abnormalitiesTimepoint: Pre-dose (-1.0 hr) to 24 hours post dose