- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03061721
Saroglitazar Magnesium in Patients With Nonalcoholic Fatty Liver Disease and/or Nonalcoholic Steatohepatitis (EVIDENCES IV)
December 30, 2023 updated by: Zydus Therapeutics Inc.
A Phase 2, Prospective, Multicenter, Double-blind, Randomized Study of Saroglitazar Magnesium 1 mg, 2 mg or 4 mg Versus Placebo in Patients With Nonalcoholic Fatty Liver Disease and/or Nonalcoholic Steatohepatitis
This is a randomized, double-blind, placebo-controlled study in up to 104 patients with a diagnosis of NAFLD and/or NASH.
The study will be conducted over a period of up to 22 weeks and will include an optional Prescreening, Screening (Days -35 to -7) Phase, a 16-week Treatment Phase following randomization on Day 1. Patients will be randomly assigned in a ratio of 1:1:1:1 to receive Saroglitazar Magnesium 1mg or 2 mg or 4 mg or matching placebo once daily in the morning before breakfast for 16 Weeks.
The primary endpoint of the study is percentage change from baseline in serum ALT levels at Week 16 in the Saroglitazar Magnesium groups as compared to the placebo group.
Study Overview
Status
Completed
Study Type
Interventional
Enrollment (Actual)
106
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Chula Vista, California, United States, 91910
- Precision Research
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Los Angeles, California, United States, 90048
- Cedars-Sinai Medical Center
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Montclair, California, United States, 91763
- Catalina Research Institute
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Pasadena, California, United States, 91105
- California Liver Research Institute
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San Diego, California, United States, 92123
- Medical Associates Research Group
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San Diego, California, United States, 92114
- Precision Research
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Florida
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Gainesville, Florida, United States, 32601
- University of Florida
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Miami, Florida, United States, 33136
- Schiff Center for Liver Diseases/University of Miami
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Orange City, Florida, United States, 32763
- Avail Clinical Research
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Indiana
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Indianapolis, Indiana, United States, 46290
- Indiana University
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Maryland
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Baltimore, Maryland, United States, 21201
- Mercy Medical Center
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Michigan
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Ann Arbor, Michigan, United States, 48109-5362
- University of Michigan
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Detroit, Michigan, United States, 48202
- Henry Ford Hospital
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Ohio
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Marion, Ohio, United States, 43302
- Awasty Research Network, LLC
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19141
- Einstein Medical Center
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Tennessee
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Germantown, Tennessee, United States, 38138
- Gastro One
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Hermitage, Tennessee, United States, 37076
- AIG Research
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Texas
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Dallas, Texas, United States, 75246
- Liver Consultants
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San Antonio, Texas, United States, 78215
- The Liver Institute
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Washington
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Seattle, Washington, United States, 89104
- Swedish Medical Center
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 73 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Males or females, 18 to 75 years of age, with body mass index (BMI) ≥ 25 kg/m2.
- Documented diagnosis of NAFLD established either by imaging (ultrasound, CT scan or MRI) or liver biopsy showing NASH or simple steatosis, within the 24 months preceding Visit 1. The diagnosis of NAFLD is made according to the American Association for the Study of Liver Diseases (AASLD) criteria (Chalasani et al. Hepatology 2012; 55:2005-2023).
- ALT level of ≥50 U/L at Visit 1 and Visit 2 with ≤30% variance between the levels at Visit 1 and Visit 2.
- Patient's demonstration of understanding of study requirements and treatment procedures, willingness to comply with all protocol-required evaluations; provision of written informed consent before any study specific tests or procedures are performed.
Exclusion Criteria:
- Consumption of > 3 units of alcohol per day (> 21 units per week) if male and > 2 units of alcohol per day (>14 units per week) if female for at least 3 consecutive months in the 5 years preceding Visit 1 (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor).
Presence of alternative causes of fatty liver, including:
- Weight change >5% within the 3 months preceding Visit 1
- Total parenteral nutrition, starvation or protein-calorie malnutrition within the 90 days preceding Visit 1.
- Use of drugs associated with NAFLD for more than 12 consecutive weeks in the 1 year before Visit 1, including amiodarone, tamoxifen, methotrexate, systemic glucocorticoids, anabolic steroids, tetracycline, estrogens in doses higher than used in oral contraceptives, vitamin A, L asparaginase, valproate, chloroquine or antiretroviral drugs
- Initiation of vitamin E at doses > 100 IU/day, or multivitamins containing > 100 IU/day of vitamin E in the 3 months preceding Visit 1.
- Use of drugs with potential effect on NASH such as ursodeoxycholic acid, S-adenosylmethionine (SAM-e), betaine, pentoxifylline, obeticholic acid or milk thistle in the 3 months prior to Visit 1.
- Changing doses of statins (simvastatin, pitavastatin, pravastatin, atorvastatin, fluvastatin, lovastatin, rosuvastatin) or fibrates (clofibrate, fenofibrate) in the 3 months preceding Visit 1.
- Use of thiazolidinediones (pioglitazone, rosiglitazone).
- Use of drugs that are known CYP2C8 inhibitors/substrate
- History of bowel surgery (gastrointestinal (bariatric) surgery or undergoing evaluation for bariatric surgery for obesity, extensive small-bowel resection or orthotopic liver transplant (OLT) or listed for OLT.
- History of other chronic liver disease (chronic hepatitis C, (HCV) infection, irrespective of their mRNA HCV assay status or active hepatitis B infection, (i.e., serum positive for hepatitis B surface antigen) or autoimmune hepatitis, cholestatic and metabolic liver diseases) or hemochromatosis
- Patient has known cirrhosis, either based on clinical criteria or liver histology.
- Patient with INR >1.3.
- Type 1 diabetes mellitus.
- Poorly controlled type 2 diabetes mellitus, i.e., glycosylated hemoglobin (HbA1c) > 9%.
Unstable cardiovascular disease, including:
- unstable angina, (i.e., new or worsening symptoms of coronary heart disease within the 3 months preceding Visit 1), acute coronary syndrome within the 6 months preceding Visit 1, acute myocardial infarction within the 3 months preceding Visit 1 or heart failure of New York Heart Association class (III - IV) or worsening congestive heart failure, or coronary artery intervention, within the 6 months preceding Visit 1
- history of (within 3 months preceding Visit 1) or current unstable cardiac dysrhythmias
- uncontrolled hypertension (systolic blood pressure [BP] > 160 mmHg and/or diastolic BP > 100 mmHg)
- stroke or transient ischemic attack within the 6 months preceding Visit 1.
- History of myopathies or evidence of active muscle disease.
- History of malignancy in the 5 years preceding Visit 1 and/or active neoplasm with the exception of resolved superficial nonmelanoma skin cancer.
Any of the following laboratory values:
- Hemoglobin < 9 g/dL
- White blood cell count < 2.5 × 103/μL
- Neutrophil count < 1.5 × 103/μL
- Platelets < 100 × 103/μL
- Total Serum bilirubin > 1.5 mg/dL (except in patient with known Gilbert bilirubin where TB up to 2.5 mg/dL is allowed), if it is <1.5 mg/dL at screening and >30% variance in the levels at Visit 1 and Visit 2
- Albumin < 3.2 g/dL
- Serum creatinine >1.5 mg/dL
- Serum ALT or AST > 250 IU/L at Visit 1 or Visit 2 .
- Contraindications to Saroglitazar Magnesium or has any conditions affecting the ability to evaluate the effects of Saroglitazar Magnesium.
- Known allergy, sensitivity or intolerance to the study drug, placebo or formulation ingredients.
- Participation in any other therapeutic clinical study within the 3 months preceding Visit 1, including participation in any other NAFLD/NASH clinical trials.
- History of bladder disease and/or hematuria or has current hematuria except due to a urinary tract infection.
- Illicit substance abuse within the 12 months preceding Visit 1.
Pregnancy-related exclusions, including:
- Pregnant/lactating female (including a positive serum pregnancy test at Visit 1)
- A male patient has to use a condom with spermicide, and the female partner of the male patient has to use an intrauterine device OR a diaphragm with spermicide OR oral contraceptive pills.
- If a male patient has undergone a vasectomy, the female partner does not have to use any contraception.
- A female patient has to use either an intrauterine device OR a diaphragm with spermicide OR oral contraceptive pills. The male partner of the female patient has to use a condom with spermicide.
- If the female patient is surgically sterilized for at least the 6 months preceding Visit 1 or postmenopausal, defined as at least 12 months with no menses and without an alternative cause, the male partner of the female patient does not have to use any contraception.
- History or other evidence of severe illness or any other conditions that would make the patient, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, HIV, coronary artery disease or active gastrointestinal conditions that might interfere with drug absorption).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Saroglitazar magnesium 1 mg
Saroglitazar magnesium 1 mg tablet orally once daily in the morning before breakfast for 16 weeks.
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Patients randomly assigned to this group will receive Saroglitazar magnesium 1 mg tablet orally once daily for 16 weeks.
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Experimental: Saroglitazar magnesium 2 mg
Saroglitazar magnesium 2 mg tablet orally once daily in the morning before breakfast for 16 weeks.
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Patients randomly assigned to this group will receive Saroglitazar magnesium 2 mg tablet orally once daily for 16 weeks.
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Experimental: Saroglitazar magnesium 4 mg
Saroglitazar magnesium 4 mg tablet orally once daily in the morning before breakfast for 16 weeks.
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Patients randomly assigned to this group will receive Saroglitazar magnesium 4 mg tablet orally once daily for 16 weeks.
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Placebo Comparator: Placebos
Placebo tablet orally once daily in the morning before breakfast for 16 weeks.
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Patients randomly assigned to this group will receive placebo tablet orally once daily for 16 weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage change from baseline in serum ALT levels at Week 16
Time Frame: 16 Weeks
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Percentage change from baseline in serum ALT levels at Week 16 in the Saroglitazar Magnesium groups as compared to the placebo group
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16 Weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in liver fat content as measured by magnetic resonance imaging-derived proton density-fat fraction (MRI-PDFF)
Time Frame: 16 Weeks
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Change in liver fat content as measured by magnetic resonance imaging-derived proton in Saroglitazar Magnesium groups as compared to the placebo group
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16 Weeks
|
Proportion of patients with sustain decrease in serum ALT levels
Time Frame: 16 Weeks
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Proportion of patients with sustain decrease in serum ALT levels in Saroglitazar Magnesium groups as compared to the placebo group
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16 Weeks
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Changes in cytokeratin-18
Time Frame: 16 Weeks
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Changes in cytokeratin-18 in Saroglitazar Magnesium groups as compared to the placebo group
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16 Weeks
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Changes in enhanced liver fibrosis
Time Frame: 16 Weeks
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Changes in enhanced liver fibrosis in Saroglitazar Magnesium groups as compared to the placebo group
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16 Weeks
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Change in aspartate aminotransferase-to-platelet ratio index
Time Frame: 16 Weeks
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Change in aspartate aminotransferase-to-platelet ratio index in Saroglitazar Magnesium groups as compared to the placebo group
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16 Weeks
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Pharmacokinetics of Saroglitazar Magnesium: maximum plasma concentration (Cmax)
Time Frame: 16 Weeks
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Maximum plasma concentration (Cmax) of Saroglitazar
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16 Weeks
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Time to reach maximum plasma concentration (Tmax)
Time Frame: 16 Week
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Time to reach maximum plasma concentration (Tmax) of saroglitazar
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16 Week
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Terminal half life (t1/2)
Time Frame: 16 Weeks
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Terminal half life (t1/2) of saroglitazar
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16 Weeks
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Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)
Time Frame: 16 Week
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Area under the curve from the time of dosing to the last measurable concentration for saroglitazar
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16 Week
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Area under the curve from the time of dosing to the infinity (AUC 0-inf)
Time Frame: 16 Week
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Area under the curve from the time of dosing to the infinity (AUC 0-inf) for Saroglitazar
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16 Week
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Elimination rate constant (λz)
Time Frame: 16 Week
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Elimination rate constant (λz) for saroglitazar
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16 Week
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Apparent volume of distribution (Vd/F)
Time Frame: 16 Week
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Apparent volume of distribution (Vd/F) for Saroglitazar
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16 Week
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Apparent clearance (CL/F)
Time Frame: 16 Week
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Apparent clearance (CL/F) for Saroglitazar
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16 Week
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Change in quality of life assessed by the Short-Form 36 Health Survey
Time Frame: 16 Week
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Quality of life will be assessed by the Short-Form 36 Health Survey
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16 Week
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Safety and tolerability of Saroglitazar Magnesium
Time Frame: 16 Weeks
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Assessed by incidence of adverse events
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16 Weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Deven V Parmar, MD,FACP,FCP, Zydus Therapeutics Inc.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012 Jun;55(6):2005-23. doi: 10.1002/hep.25762. No abstract available.
- Gawrieh S, Noureddin M, Loo N, Mohseni R, Awasty V, Cusi K, Kowdley KV, Lai M, Schiff E, Parmar D, Patel P, Chalasani N. Saroglitazar, a PPAR-alpha/gamma Agonist, for Treatment of NAFLD: A Randomized Controlled Double-Blind Phase 2 Trial. Hepatology. 2021 Oct;74(4):1809-1824. doi: 10.1002/hep.31843. Epub 2021 Jul 19.
Helpful Links
- Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of
- Gawrieh S, Noureddin M, Loo N, Mohseni R, Awasty V, Cusi K, Kowdley KV, Lai M, Schiff E, Parmar D, Patel P, Chalasani N. Saroglitazar, a PPAR-alpha/gamma Agonist, for Treatment of NAFLD: A Randomized Controlled Double-Blind Phase 2 Trial.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 6, 2017
Primary Completion (Actual)
October 30, 2020
Study Completion (Actual)
December 15, 2020
Study Registration Dates
First Submitted
February 7, 2017
First Submitted That Met QC Criteria
February 17, 2017
First Posted (Actual)
February 23, 2017
Study Record Updates
Last Update Posted (Actual)
January 5, 2024
Last Update Submitted That Met QC Criteria
December 30, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- SARO.16.005
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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