Phase I Multiple Ascending Dose study of TRC150094 on overweight/obese male and female subjects.
Scientific Title of Study
A Phase I, Double-blind, Placebo-controlled, Randomized, Multiple-dose, Dose-ascending Study to Evaluate the Safety, Tolerability, Pharmacokinetics and to explore Pharmacodynamic trends after oral administration of TRC150094 in Overweight/Obese Male and Female Subjects with other non traditional CV risk factors.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CT/P015/MS/2010/01_02
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Manjunath K
Designation
Affiliation
Address
Lambda Therapeutic Research Limited S.G. Highway, Gota, Ahmadabad GUJARAT 380061 India
Phone
079-40202290
Fax
Email
manjunathk@lambda-cro.com
Details of Contact Person Scientific Query
Name
Dr. Lalit Lakhwani
Designation
Affiliation
Address
Torrent Research Centre Village Bhat Gandhinagar GUJARAT 382428 India
Phone
079-23969100
Fax
079-23969135
Email
lalitlakhwani@torrentpharma.com
Details of Contact Person Public Query
Name
Dr. Lalit Lakhwani
Designation
Affiliation
Address
Torrent Research Centre Village Bhat Gandhinagar GUJARAT 382428 India
1. Medical history, physical examination, vital signs, clinical laboratory tests, 12-lead ECG and Chest X ray without significant abnormalities, in the opinion of the investigator
2. Overweight/obese adult male and female in the age range 18-65 years, inclusive, with a BMI in the range 27-35 kg/m2, inclusive
3. Waist circumference: men more than or equal to 90 cm, women more than or equal to 80 cm
4. Subjects with Non-alcoholic Fatty liver Grade 1-3 based on Magnetic Resonance Spectroscopy. (Ref Qayyum A)
5. Fasting serum insulin more than or equal to 10mU/ml and Fasting plasma glucose >100 mg/dl
6. Blood pressure: SBP more than or equal to 130 mmHg or DBP more than or equal to 85 mmHg or subjects
receiving anti-hypertensive treatment
7. Serum triglyceride (fasting) more than or equal to 150 mg/dL
8. Female subjects will include with/without childbearing potential using highly effective method of contraception except OCPs from at least 15 days prior to enrolment till 10 days after administration of last dose.
9. Negative drugs of abuse test and negative alcohol breath test
10. Non-smokers or current smokers who have been smoking less than 10 cigarettes (or equivalent) per day on a stable basis for at least 3 months prior to Day 1 and who are willing to stop smoking / tobacco intake during the study period(s).
11. Ability to communicate well with the investigator and to comply with the requirements of the entire study.
12. Willingness to give written informed consent (prior to any studyrelated procedures being performed) and ability to adhere to the study restrictions and assessments schedule.
ExclusionCriteria
Details
1. Clinically relevant abnormal physical findings at the screening
examination, which would interfere with the objectives of the study.
2. Clinically significant abnormalities in the results of the clinical
laboratory tests (at screening or Day (-1).
3. eGFR < 60 mL/min/1.73m2 as evaluated by Modification of Diet in Renal Disease (MDRD) method.
4. History of angina, Myocardial Infarction (MI) or stroke since last 6 months.
5. Angina or evidence of myocardial ischemia in ECG during CPET
6. Severe joint disease or peripheral arterial disease sufficient to impede exercise testing
7. Clinically relevant abnormalities in the 12-lead ECG (at screening or Day -1).
8. Hypertension with SBP/DBP more than or equal to 170/110 m Hg.
9. ALT or AST more than or equal to ULN*3
10. History or presence of malignancy.
11. Addiction to alcohol or history of any alcohol or drug abuse.
12. History of allergy to the test drug or any drug chemically similar to the drug under investigation.
13. Positive for HIV I, HIV II, hepatitis C antibody or HBsAg.
14. Positive for urine drugs of abuse test (at screening or Day -1).
15. Subjects suffering from any psychiatric (acute or chronic) illness.
16. Intake of any medication except those permitted in this study
17. Intake of any investigational drug in the period within 3 months prior to the first dose of study drug.
18. History of significant blood loss due to any reason, including blood donation, in the 12 weeks prior to the first dose of study drug; or the total blood loss in the last 3 months, including for this study, exceeds 450 mL.
19. History of any bleeding disorder.
20. Existence of any surgical or medical condition which, in the judgment of the principal investigator, might interfere with the absorption, distribution, metabolism or excretion of the study drug or might be likely to compromise the safety of the subject.
21. Inability to communicate or co-operate with the investigator because of language problems, poor mental development or impaired cerebral function.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
To evaluate the safety and tolerability of ascending multiple doses of TRC150094 in overweight/obese male and female volunteers. It includes physical examination, clinical laboratory tests, vital signs and 12-lead ECG.
PHYSICAL EXAMINATION: Day -2,Day 7, 14, 21, 30, post study follow-up visit. CLINICAL LABORATORY TESTS: Day −1, Day 7: pre-dose (before dosing), Day 14: pre-dose (before dosing), Day 21: pre-dose (before dosing), Day 29: 24 hour post dose (after dosing on Day 28), post-study follow-up visit. VITAL SIGNS: Day -2,Day -1, Day 1: pre-dose (0), 0.5, 1, 2, 4, 6, 8, 12, 24, Day 2-27: at 12 hr intervals, Day 28: pre-dose (0), 0.5, 1, 2, 4, 6, 8, 12, 24, Day29-30: at 12 hr intervals, Post-study follow-up visit. 12-LEAD ECG: Day -2, Day -1, Day 1: pre-dose (0), 0.5, 1, 4, 8 and 12 hours post-dose, Day 2-30: 24 hr intervals, Post-study follow-up visit.
Secondary Outcome
Outcome
TimePoints
To study the pharmacokinetics of TRC150094 in overweight/obese male and female volunteers. To explore early efficacy markers in overweight/obese male and female volunteers.
(I)PHARMACOKINETICS: PLASMA SAMPLE: Day 1: Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 12, 18 and 24 hrs post dose (14 samples) Day 3-8, 15, 22: Predose (8 Samples) Day 28: Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 12, 18, 24, 48 hrs, Ambulatory - 72hr, 96hr post dose (17 samples) URINE SAMPLE: Day 1: pre-dose collection (bladder must also be emptied before dosing), 0-4, 4-8, 8-12 and 12-24 hours postdose. Day 28: pre-dose collection (bladder must also be emptied before dosing), 0-4, 4-8, 8-12, 12-24 and 24-48 hours post-dose (relative to the dose on Day 28). (II) EARLY EFFICACY MARKERS: OGTT: Day-1, Day 26. HEPATIC FAT BY MRS: At baseline (staggered at day -1, -2), day 27 (staggered at day 27 and day 29). CPET: At baseline (staggered at day -1, -2), day 27 (staggered at day 27 and day 29). SERUM TRIGLYCERIDES: AS per clinical laboratory test timepoints.
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This study will be a Single centre, double-blind, placebo-controlled, randomized, multiple-dose, dose-ascending study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics after oral administration of TRC150094 to overweight/obese male and female subject with other non traditional CV risk factors. The study will be conducted in India. The study will last for about 6 months. The primary outcome measures will include the assessment of Safety and Tolerability of the study drug, which will be done by assessing Adverse events at different time points, by evaluating 12 Lead ECG's, by performing physical examination at different time points and by measuring vital signs and clinical labaoratory tests. The secondary outcome measures include the pharmacokinetic measurements and early efficacy markers that will include hepatic fat, HOMA-IR, CPET parameters and serum triglycerides.