| CTRI Number |
CTRI/2015/10/006236 [Registered on: 05/10/2015] Trial Registered Prospectively |
| Last Modified On: |
13/11/2019 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Saroglitazar 4 mg in treatment of Non-Alcoholic Steatohepatitis |
Scientific Title of Study
Modification(s)
|
A Prospective, Multi-centre, Double-blind, Randomized Trial of Saroglitazar 4Â mg versus Placebo in Patients With Non-Alcoholic Steatohepatitis |
| Trial Acronym |
PRESS XI |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| SARO.14.001.03.PROT,Version 3.0 dated 17.08.2016 |
Protocol Number |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Dr Manjunath K |
| Designation |
Deputy General Manager |
| Affiliation |
Cadila Healthcare Limited |
| Address |
Zydus Research Center,
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A
Moraiya,
Ahmadabad
GUJARAT
382213
India |
| Phone |
91-2717-665555 |
| Fax |
91-2717-665355 |
| Email |
Manjunath.K@zyduscadila.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Manjunath K |
| Designation |
Deputy General Manager |
| Affiliation |
Cadila Healthcare Limited |
| Address |
Zydus Research Center,
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A
Moraiya,
Ahmadabad
GUJARAT
382213
India |
| Phone |
91-2717-665555 |
| Fax |
91-2717-665355 |
| Email |
Manjunath.K@zyduscadila.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Dr Manjunath K |
| Designation |
Deputy General Manager |
| Affiliation |
Cadila Healthcare Limited |
| Address |
Zydus Research Center,
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A
Moraiya,
Ahmadabad
GUJARAT
382213
India |
| Phone |
91-2717-665555 |
| Fax |
91-2717-665355 |
| Email |
Manjunath.K@zyduscadila.com |
|
|
Source of Monetary or Material Support
|
| Cadila Healthcare Limited, Zydus Cadila House, Plot No. 360, TPS 5, Dayaldas Road
- Service Road Crossing, Vile Parle (E), Mumbai-400057,
|
|
|
Primary Sponsor
|
| Name |
Cadila Healthcare Limited |
| Address |
Cadila Healthcare Limited, Zydus Cadila House, TPS 5, Service road, Vile Parle (E), Mumbai-400057, Maharashtra, India |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 13 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Vinod Kumar Dixit |
Banaras Hindu University |
Department Of Gastroenterology, IMS,Banaras Hindu University,varanasi 221005
Varanasi
UTTAR PRADESH |
9415202449
drvkdixit@gmail.com |
| Dr Purshottam Koradia |
BAPS Pramukhswami Hospital |
BAPS Pramukhswami Hospital Adajan, Surat
Surat
GUJARAT |
9825312027
purushottam_koradia@yahoo.co.in |
| Dr Ajay Duseja |
Department of Hepatology |
Department of Hepatology,PGIMER,Chandigargh-160012
Chandigarh
CHANDIGARH |
9417007416
ajayduseja@yahoo.co.in |
| Dr Lata Prasad |
Global Hospitals |
Global Hospitals, Lakdikaphool, Hyderabad,500004
Hyderabad
ANDHRA PRADESH |
9490115664
lataprsd@yahoo.com |
| Dr Dinesh Kumar Jothimani |
Global Hospitals and Health city |
Global Hospitals and Health city, Perumbakkam
Chennai
TAMIL NADU |
9176599555
jdineshis@yahoo.co.uk |
| DrManoj Kumar Sharma |
Institute of Liver and Biliary Sciences |
Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi -110070
New Delhi
DELHI |
9313416555
manojkumardm@gmail.com |
| DrMurugesh Mallaiyappan |
Kovai Diabetes Speciality Centre & Hospital |
No.15, Vivekananda Road, Ramnagar, Coimbatore-641009, Tamilnadu, India
Coimbatore
TAMIL NADU |
9442600500
mmcmurugesh@gmail.com |
| DrN K Malpani |
Malpani Multispecialty Hospital |
SP-6, Road No. 1, VKI Area, Sikar Road, Jaipur-302013
Jaipur
RAJASTHAN |
9414169090
nkdocmalpani@gmail.com |
| Dr Shrikant Vasantrao Mukewar |
Midas Multispeciality hospital Pvt. Ltd |
Midas Height ,07,
Central Bazar Road,
Ramdaspeth, Nagpur 440010
Nagpur
MAHARASHTRA |
7720033280
Shrikant_mukewar@yahoo.com |
| Dr Sandeep Nijhawan |
S M S Medical College Hospital |
Department of Gastroenterology, S M S Medical College Hospital, Jaipur -302004, Rajasthan
Jaipur
RAJASTHAN |
9829272233
dr_nijhawan@yahoo.com |
| DrSaraswat V A |
Sanjay Gandhi Postgraduate Institute of medical sciences |
Department of Gastroenterology , Sanjay Gandhi Postgraduate Institute of medical sciences, Raebareli Road, Luck now, (UP)India 226014
Lucknow
UTTAR PRADESH |
9415004007
profviveksaraswat@gmail.com |
| Dr Shobna Bhatia |
Seth G.S Medical College and K.E.M Hospital |
Department of Gastroenterology, Seth G.S Medical College and K.E.M Hospital,Parel,Mumbai-400012
Mumbai
MAHARASHTRA |
9869072213
sjb@kem.edu |
| Dr Shrihari Dhorepatil |
Shri Hospital |
Siddharth Mansion, Nagar Road
Pune – 411006
Maharashtra – India
Pune
MAHARASHTRA |
9822040769
Sdhorepatil@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 13 |
| Name of Committee |
Approval Status |
| Ethics Committee Midas multispeciality Hospital Pvt Ltd |
Approved |
| Ethics Committee Shree Hospital , 5th Floor, Siddharth Mission Nagar Raod , Pune – 411004 Maharashtra – India |
Approved |
| Ethics Committee,Institute of Medical sciences,Banaras Hindu University, Varansi-221005 |
Approved |
| Institutional Ethics Committee II |
Approved |
| Institutional Ethics Committee of Kovai Diabetes Speciality Centre & Hospital |
Approved |
| Institutional Ethics Committee, BAPS PRAMUKH SWAMI HOSPITAL |
Approved |
| Institutional Ethics Committee, Global Hospital and Health City Chennai |
Approved |
| Institutional Ethics Committee, Global Hospitals, Hyderabad |
Approved |
| Institutional Ethics Committee, Institute of Liver and Biliary Sciences |
Approved |
| Institutional Ethics Committee, Maplani Multispeciality Hospital |
Approved |
| Institutional Ethics Committee, PGIMER |
Approved |
| Institutional Ethics Committee, SGPIMS |
Approved |
| Office of the Ethics Committe SMS Medical College |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Nonalcoholic Steatohepatitis, (1) ICD-10 Condition: K758||Other specified inflammatory liverdiseases, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Placebo |
Route:- Oral
Frequency :-Once daily Duration :-52 weeks |
| Intervention |
Saroglitazar 4mg |
Dosage:-4 Mg
Route:- Oral
Frequency :-Once daily
Duration :-52 weeks
|
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
75.00 Year(s) |
| Gender |
Both |
| Details |
Patients provide written informed consent for participation in this trial.
Male or female, aged from 18 to 75 years
Female must be either of non-child bearing potential (surgically sterilized at least 6 months prior to screening or postmenopausal) or using one or more methods of contraception.
Histologic confirmation of NASH without cirrhosis (fibrosis stage 1, 2, or 3) from liver biopsy performed either during the Screening period or within 6 months prior to the first visit with a NAS of ≥ 4 with a score of at least 1 in each component (steatosis, lobular inflammation, and hepatocyte ballooning). If biopsy is done within 6 months, the slides, biopsy material or block should be available for baseline documentation. Such patients, whose historical biopsy report available, should not use medications suspected of having an effect on NASH from the 3 months prior to the biopsy.
For hypertensive patients, blood pressure must be controlled by stable dose of anti hypertensive medications for at least 2 months prior to biopsy (and the stable dose can be maintained throughout the study)
Patients agree to comply with the study procedure. |
|
| ExclusionCriteria |
| Details |
Pregnancy and lactating female.
Positive pregnancy test.
Patients with history of myopathies or evidence of active muscle diseases
Patients with history of alcohol consumption of > 30 gm/week for men, >20 gm/week for women for 3 consecutive months in the last 5 years and/or drug abuse.
Known allergy, sensitivity or intolerance to the study drug, placebo, or formulation ingredients.
Participation in any other clinical trial in past 3 months other than survey based studies.
History of malignancy in the past 5 years and/or active neoplasm with the exception of superficial, non-melanoma, skin cancer.
Patients having unstable angina, Acute Myocardial Infarction in past 3 months or heart failure of NYHA class (III-IV).
New or worsening symptoms of coronary heart disease within the past three months or has any of the following within the past 6 months: ACS, worsening congestive heart failure (CHF), coronary artery intervention, stroke or Transient Ischemic Attack.
Previous history of bladder disease and/or hematuria. Current hematuria except due to Urinary Tract Infection.
Previous liver biopsy that demonstrated presence of cirrhosis or radiologic imaging consistent with cirrhosis or portal hypertension.
Type 2 diabetes treated with agents other than Metformin, sulfonylureas and DPP4 inhibitors.
Type 1 diabetes mellitus.
Patient on Fibrates (Other anti-dyslipidemic drugs will be allowed provided dose is stable in last 3 months before biopsy and the stable dose can be maintained throughout the study).
Use of drugs associated with a clinical or histological picture consistent with fatty liver disease or NASH for more than 12 consecutive weeks in the 1 year prior to start of the study; (these include amiodarone, tamoxifen, methotrexate, glucocorticoids, anabolic steroids, tetracyclines, estrogens, valproate/valproic acid, chloroquine, anti-HIV drugs).
History of thyroid disease. Hypothyroid patients who are euthyroid on thyroid hormone replacement can be included.
Uncontrolled Hypertension (>140 mmHg Systolic and / or >90 mmHg Diastolic).
History of, or current cardiac dysrhythmias.
History of bariatric surgery, or undergoing evaluation for bariatric surgery.
Patients on weight loss regimen (≥5% weight loss) in last 8 weeks prior to diagnostic liver biopsy.
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, coronary artery disease, or active gastrointestinal conditions that might interfere with drug absorption).
Patient on any treatment with other drugs used for treatment of NASH [Pentoxyphyllin, Ursodeoxycholic acid, antioxidants such as vitamin E (>400IU/day), glutathione, Orlistat, Betaine, incretin mimetics or non-prescribed complementary alternative medications (including dietary supplements, megadose vitamins, herbal preparations, and special teas)] or any medicine in clinical trials for NASH [6].
History of other cause of chronic liver disease [autoimmune, primary biliary cirrhosis, hepatitis B virus (HBV) and hepatitis C virus (HCV), Wilson, alpha-1-antitrypsin deficit, hemochromatosis etc.] i.e. Antinuclear antibodies (ANA) > 1:160, Anti-smooth muscle Ab positive >1:160 , Serum hepatitis B surface antigen (HepBsAg) positive, Serum hepatitis C antibody (HepC Ab) positive, transferrin saturation > 45%.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Pre-numbered or coded identical Containers |
|
Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
To assess the decrease in NAFLD Activity Score (Time frame 52 weeks)
Define by patients with NASH after 52 weeks of treatment Saroglitazar will show a decrease in NAFLD Activity Score (NAS) by at least 2 points spread across at least 2 of the NAS components [steatosis, hepatocyte ballooning, and lobular inflammation] with no worsening of fibrosis in greater proportion of patients compared to placebo.
|
52 weeks |
|
Secondary Outcome
Modification(s)
|
| Outcome |
TimePoints |
1.Percentage of responders, defined by the disappearance of steatohepatitis
2.Stage of steatosis, lobular inflammation and ballooning
3.Stage of fibrosis Area of fibrosis
4.Liver function test
5.Lipid profile and lipoprotein
6.Insulin resistance and glycemic control
|
52 weeks |
|
|
Target Sample Size
|
Total Sample Size="102"
Sample Size from India="102"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
Date of First Enrollment (India)
Modification(s)
|
09/07/2016 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="4"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
NA |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Very few trials have been conducted with drugs having definite therapeutic benefits in NASH and, as a consequence, no specific therapy has been approved for this condition.
Saroglitazar has been tested in Phase II for NASH at 4 mg dosage form and demonstrated statistically significant reduction of Alanine Aminotransferase (ALT) levels compared to placebo which was measured as the primary endpoint.
Considering the encouraging results from the Phase II study, Saroglitazar is expected to favorably ameliorate insulin resistance and modulate lipid and glucose metabolism leading to reduced hepatic inflammation with a resultant reduction in NASH and improvement in other metabolic endpoints with minimal side effects. |