Clinical trial NCT03097107: Evaluate the Safety and Efficacy of Saroglitazar Mg in Patients With Fasting Triglyceride ≥500 mg/dL and ≤1500 mg/dL
Official title: Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Arm, 12-week Study to Evaluate the Safety and Efficacy of Saroglitazar Magnesium 1, 2 and 4 mg in Patients With Fasting Triglyceride ≥500 mg/dL and ≤1500 mg/dL
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Dyslipidemias
Keywords: hypertriglyceridemia
dyslipidemia
saroglitazar magnesium
lipid disorder
Lead sponsor: Zydus Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2017-03-31
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy of Saroglitazar Magnesium 1, 2, and 4 mg in patients with fasting triglyceride ≥500 mg/dL and ≤1500 mg/dL.

Detailed description: SARO.15.001.04 is a multicenter, prospective, randomized, double-blind, placebo-controlled, parallel arm, 12-week study designed to evaluate the safety and efficacy of Saroglitazar Magnesium 1, 2 and 4 mg in patients with fasting triglyceride ≥500 mg/dL and ≤1500 mg/dL.

A total 124 subjects will be enrolled in a ratio of 1:1:1:1 to receive either Saroglitazar Magnesium 1 mg, Saroglitazar Magnesium 2 mg, Saroglitazar Magnesium 4 mg, or placebo.

Eligibility criteria: Inclusion Criteria:

1. Adults subjects (≥18 year) of either gender.
2. Average fasting TG-C ≥500 mg/dL and ≤1500 mg/dL (from Visits 2 and 2.1).
3. Able and willing to give written informed consent and comply with the requirements of the study protocol.

Exclusion Criteria:

1. History of pancreatitis within 6 months of the initial screening visit (Visit 1); patients that have an episode of pancreatitis after Visit 1 but before randomization will not be randomized.
2. Patients with any history of pancreatitis may not be on GLP-1 agonists, DPP-4 inhibitors or pramlintide, with their last dose no sooner than 3 months prior to Visit 1; use of these agents by this population is prohibited throughout the duration of the trial and follow-up period. \[Patients without a history of pancreatitis on these agents must be on a stable dose as of 3 months prior to Visit 1.\]
3. History of \>5% weight gain or weight loss or participation in weight gain/loss program in past 3 months and not in the maintenance phase as of Visit 1.
4. Diabetic (as per ADA guideline) patients with HbA1c \>9.5 %.
5. Patients on prandial/rapid acting insulin, thiazolidinediones (TZDs) or glitazars in the 3 months prior to Visit 1.
6. Patients on unstable doses of basal insulin (i.e., glargine, detemir, NPH) with unstable defined as a greater than 20% fluctuation in daily dose within the past 3 months.
7. Patients on anti-obesity medications within 6 months of Visit 1 (orlistat, lorcaserin, phentermine, naltrexone/bupropion etc.).
8. Patients on drugs that may promote weight loss (i.e., anti-epileptic agents such as topiramate, zonisamide and the anti-depressant bupropion) may not be taken, unless the dose is stable for 3 months and the indication for use is not weight loss.
9. Patients on prohibited nutraceutical supplements contained in Annexure 1 that are unwilling to wash-out starting at Visit 1 (and abstain from use throughout the duration of the study, including follow-up).
10. Patients with unexplained hematuria prior to or first noted during Visit 1.
11. Patients with anemia who are undergoing repletion of deficiencies (iron, folate, B12) not in the maintenance phase as of Visit 1.
12. Patients on concomitant lipid-lowering medications and not willing to participate in Lead-in/Run-in Phase (Please refer Lead-in/Run-in Phase).
13. Patients having heart failure of NYHA class (III-IV), unstable angina, acute myocardial infarction, stroke, transient ischaemic attack, any coronary revascularisation procedure and hospitalization for acute coronary syndrome and discharge within 6 months prior to screening.
14. Patients with Left Ventricular dysfunction (Left Ventricular Ejection Fraction (LVEF) \<40%, as measured through ECHO).
15. Uncontrolled hypertension (SBP \>160 and/or DBP\>100).
16. An uncontrolled thyroid disorder

    * Uncontrolled hyperthyroidism is defined as any history of hyperthyroidism that has either not been treated with either radioactive iodine (RAI) and/or surgery -or- that has been treated with RAI and/or surgery, but has required ongoing continuous or intermittent use of thyroid hormone synthesis inhibitors (i.e., methimazole or proplythiouracil) within 6 months of Visit 1.
    * Uncontrolled hypothyroidism is defined as initiation of thyroid hormone replacement therapy or dose adjustment of replacement therapy within 3 months of Visit 1.
17. History of GI malabsorption or history of gastric bypass, banding, or diversional bariatric surgery.
18. History of active liver disease or gall stones or hepatic dysfunction demonstrated by AST and ALT ≥2 times of upper normal limit (UNL) or bilirubin ≥1.5 times UNL at Visit 1.
19. History of myopathies or evidence of active muscle diseases demonstrated by CPK ≥5 times UNL at Visit 1.
20. History of any other concurrent serious illness or malignancy (except successfully treated basal and squamous cell carcinoma of the skin), within the past 5 years (e.g. tuberculosis, HIV).
21. Positive HIV, hepatitis A (positivity of IgM), hepatitis B, or hepatitis C at Visit 1.
22. History of excessive consumption of alcoholic beverages (consumes \>2 alcoholic drinks per day or \>14 alcoholic drinks per week, or engages in binge drinking). For the remainder of the study, patients should agree to refrain from excessive alcohol consumption (i.e., \>2 alcoholic beverages per day), to maintain their current dietary regimen, and to not alter their normal activity routines. (Note: patients should not drink alcohol for at least 24 hrs prior to any site visit).
23. History of known allergy, sensitivity or intolerance to the study drugs and their formulation ingredients.
24. Renal dysfunction demonstrated by abnormal eGFR \<50 mL/min/1.73 m2.
25. History of clinically significant\* systemic steroid therapy (intramuscular, intravenous, intra-articular, or oral route) within 3 months of the Visit 1 or anticipated requirement for systemic steroid therapy at Visit 1(however, topical, ophthalmic and inhaled steroids are allowed).

    \* Clinically significant' (i.e., no more than 5 days of systemic steroids treatment within 3 months of Visit 1)
26. NSAID use in excess of a reasonably prescribed dose and/or use in individuals with a history of complications resulting from these agents.
27. Participation in any other clinical trial in the past 3 months in which investigational product was taken and/or a medical device was utilized. Patients that were screened but not randomized for another study must wait 30 days to participate in Visit 1.
28. Pregnancy (including a positive urine and serum pregnancy test at Visit 1), lactation or planned pregnancy/lactation during any time during the lead-in, study or follow-up periods.
29. Patients on hormonal contraception or hormone replacement therapy containing estrogen (progesterone based contraception and testosterone replacement therapy are permitted granted that dosing is stable for at least 3 months prior to Visit 1).
30. Women of childbearing potential (WOCBP) and men, UNLESS using effective contraceptive methods, such as an intra-uterine device or other mechanical contraception method with condom or diaphragm and spermicide) throughout the study. For male patients, contraception measures (condom and spermicide) must be taken during the study, either by the male participant or his female partner. (Note: Enrolled females otherwise must be surgically sterilize for at least the 6 months preceding Visit 1 or postmenopausal, defined as 12 months with no menses without an alternative medical cause).

Primary outcomes:
measure: Percentage change in triglyceride cholesterol levels
timeFrame: 12 Weeks
Secondary outcomes:
measure: Percentage change in TG-C
timeFrame: 8 Weeks
measure: Percentage change in lipid profile.
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Medical Affiliated Research Center, Inc.
state: Alabama
city: Encinitas
country: United States
facility: Encompass Clinical Research
state: California
city: San Diego
country: United States
facility: Integrated Research Center
state: California
city: Ventura
country: United States
facility: Ventura Clinical Trials
state: California
city: Colorado Springs
country: United States
facility: Colorado Springs Health Partners
state: Colorado
city: Bradenton
country: United States
facility: Meridien Research - Bradenton
state: Florida
city: Lakeland
country: United States
facility: Meridien Research - Lakeland
state: Florida
city: Oviedo
country: United States
facility: Oviedo Medical Research, LLC
state: Florida
city: Tampa
country: United States
facility: Meridien Research - Tampa
state: Florida
city: Blue Ridge
country: United States
facility: River Birch Research Alliance LLC
state: Georgia
city: Marietta
country: United States
facility: Drug Studies America
state: Georgia
city: Suwanee
country: United States
facility: Herman Clinical Research, LLC
state: Georgia
city: Chicago
country: United States
facility: Cedar-Crosse Research Center
state: Illinois
city: Newton
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Elkridge
country: United States
facility: Centennial Medical Group
state: Maryland
city: Oxon Hill
country: United States
facility: MD Medical Research
state: Maryland
city: Butte
country: United States
facility: Mercury Street Medical
state: Montana
city: Charlotte
country: United States
facility: Einstein Clinical Research
state: North Carolina
city: Greensboro
country: United States
facility: Triad Clinical Trials LLC
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Metabolic and Atherosclerosis Research Center
state: Ohio
city: Cincinnati
country: United States
facility: Sterling Research Group, Ltd.
state: Ohio
city: Kettering
country: United States
facility: Wells Institute for Health Awareness
state: Ohio
city: Lyndhurst
country: United States
facility: Ohio Clinical Research - Lyndhurst
state: Ohio
city: Marion
country: United States
facility: Awasty Research Network, LLC
state: Ohio
city: Willoughby Hills
country: United States
facility: Ohio Clinical Research, LLC - Willoughby Hills
state: Ohio
city: Portland
country: United States
facility: Columbia Research Group, Inc.
state: Oregon
city: Bristol
country: United States
facility: PMG Research of Bristol, LLC
state: Tennessee
city: Jackson
country: United States
facility: Jackson Clinic
state: Tennessee
city: Houston
country: United States
facility: Pioneer Research Solutions Inc.
state: Texas
city: Richmond
country: United States
facility: National Clinical Research - Richmond, Inc
state: Virginia
Study officials:
affiliation: Zydus Therapeutics Inc.
name: Deven V Parmar, MD
role: STUDY_DIRECTOR
References: