Phase I Multiple Ascending Dose study of TRC150094 on overweight/obese male and female subjects.

Phase 1

Completed

Conditions: Metabolic Syndrome

Registration Number: CTRI/2009/091/000601

Lead Sponsor: Torrent Pharmaceuticals Limited

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 28

Inclusion Criteria

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.
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.
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).
Ability to communicate well with the investigator and to comply with the requirements of the entire study.
Willingness to give written informed consent (prior to any studyrelated procedures being performed) and ability to adhere to the study restrictions and assessments schedule.

Exclusion Criteria

Clinically relevant abnormal physical findings at the screeningexamination, which would interfere with the objectives of the study.2. Clinically significant abnormalities in the results of the clinicallaboratory 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 CPET6.
Severe joint disease or peripheral arterial disease sufficient to impede exercise testing7.
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*310.
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.
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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Measures

Name	Time	Method
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.

Trial Locations

Locations (1): Lambda Therapeutic Research Limited
🇮🇳
Ahmadabad, GUJARAT, India
Lambda Therapeutic Research Limited
🇮🇳Ahmadabad, GUJARAT, India
Dr Manjunath K
Principal investigator
079-40202290