A clinical trial to assess the effect of Linaclotide in patients with chronic constipation
Scientific Title of Study
A RANDOMIZED, MULTICENTRE, DOUBLE BLIND, PLACEBO CONTROLLED,
PARALLEL-GROUP, STUDY TO EVALUATE THE EFFICACY AND SAFETY OF
LINACLOTIDE ONCE DAILY OF DR. REDDY’S LABORATORIES LIMITED IN
PATIENTS WITH CHRONIC CONSTIPATION
Ring Road, Gunadala, Vijayawada – 520008, Andhra Pradesh, India Krishna ANDHRA PRADESH
9440883800
drjagan602000@gmail.com
Dr Anjan Jyoti Talukdar
Guwahati Medical College
Ground Floor, Department of Medicine, Guwahati, Bhangagarh, Assam 781032 Kamrup ASSAM
9954658926
dranjan_t@yahoo.co.in
Dr Srijan Majumdar
Indian Institute of Liver and Digestive Science
Mandira 3rd floor, Center for clinical research, gastroenterology, Sitala East, Sonarpur, Kolkata - 700150
South Twentyfour Parganas WEST BENGAL
9869107887
sri1981m@gmail.com
Dr Vishwa Mohan Dayal
Indira Gandhi Institute of Medical Sciences
 Room No. 181, 3rd Floor, Department of Gastroenterology, OPD Building, Sheikhpura, Patna, Bihar-800014
Patna BIHAR
9473191808
vmdayal@gmail.com
Dr DP Yadav
Institute of Medical Sciences, BHU
Room no. 5, 2nd Floor, Department of gastroenterology, Varanasi- 221005, India Varanasi UTTAR PRADESH
8130856563
devesh.thedoc@gmail.com
Dr Santosh Hajare
K.L.E Prabhakar Hospital
2nd floor, Department of gastroenterology, Nehrunagar Belagavi-590010 Karnataka India Belgaum KARNATAKA
9448111913
drsantoshhajare@gmail.com
Dr Ajay Kumar
King Georges Medical University
 2nd floor, gandhi department, Department of medicine, Kalam Center, Room No. 505, 5th Floor, Shahmeena Road, Chowk, Lucknow-226003. Lucknow UTTAR PRADESH
9455519306
drajaymd12345@gmail.com
Dr Vivek Bhatia
Maharaja Agrasen Hospital
Room no. 3, gtound floor, department of gastroenterology, Near Metro Station Jain Muni Guru Ramkrishan Marg, Block C, Shivaji Park, Punjabi Bagh, Delhi, 110026 West DELHI
9811028897
drvivekbhatia@yahoo.co.in
Dr Tryambak Samanta
Medical College and Hospital
5th floor, faculty room, Department of medical gastroenterology, Super specialty building, 88 College street, Kolkata-700073, West Bengal, India Kolkata WEST BENGAL
8777530352
drts.india@gmail.com
Dr Nemade Pankaj Ramesh
Medipoint Hospitals Pvt. Ltd.
241/1, New D.P.Road, Aundh, Pune ,Maharashtra – 411007, India Pune MAHARASHTRA
8087521353
drpankajnemade.medipoint@gmail.com
Dr Gaurav Garg
Motilal Nehru Medical College
George Town, Prayagraj, Uttar Pradesh – 211002, India Allahabad UTTAR PRADESH
9528766749
drgaurav.g9@gmail.com
Dr Manas Kumar Mondal
Nil Ratan Sircar Medical College and Hospital
2nd floor, OPD Building, Room no. 8, Department of Gastroenterology, 138, A.J.C Bose Road, Kolkata- 700014, West Bengal, India.
Kolkata WEST BENGAL
9073593883
mkmondal_1979@yahoo.in
Dr Sujoy Sarkar
North Bengal Medical College & Hospital
Sushruta Nagar, Siliguri, Darjeeling
West Bengal – 734012 Darjiling WEST BENGAL
7980620211
drsujoy2@gmail.com
Dr B Ramesh Kumar
Osmania General Hospital
 Liver Care Unit, NPR block, 1st Floor, Research Wing, Department of Gastroenterology, Osmania General Hospital, Afzalgunj, Hyderabad-500012, Telangana, India
Hyderabad TELANGANA
9949043290
bhashyakarla_rk@yahoo.co.in
Dr Saroj Kant Sinha
Post Graduate Institute of Medical Education & Research
F- block, Groun floor, Department of gastroenterology, Sector 12 Chandigarh- 160012, India Chandigarh CHANDIGARH
7087009614
sarojksinha@hotmail.com
Dr Prasita Kshirsagar
Rajiv Gandhi Medical College and Chatrapati Shivaji Maharaj Hospital
1st floor, department of medicine, Agra, near Central Library Moti Katra Mantola Agra, Uttar Pradesh- 282003 Agra UTTAR PRADESH
9319250485
prabhatagrawal321@gmail.com
Dr Shweta Borkar
Shalinitai Meghe Hospital and Research Center
Study room no 01, Central clinical laboratory, 1st floor, clinical research division, Department of General medicine, Wanadongori, Nagpur 441110 Nagpur MAHARASHTRA
9819423980
drshwetaborkar@gmail.com
Dr Ashok Jhajharia
SMS Medical College and HospitalÂ
 Ground floor, Dept. of Gastroenterology,JLN Marg,Jaipur, Rajasthan -302004, IndiaÂ
Jaipur RAJASTHAN
9785833839
drashokjhajharia@gmail.com
Dr Mohini Singh
Sri Ramachandra Hospital
Room no. 09, Dental college basement floor, Department of gastroenterology, Road No. 1, Ramachandra Nagar, Porur Chennai- 600116 Chennai TAMIL NADU
Penta-Med Ethics Committee Medipoint Hospitals Pvt. Ltd. Pune
Approved
The Institutional Clinical Ethics Committee; Rajiv Gandhi Medical College and Chatrapati Shivaji Maharaj Hospital, Kalwa, Thane
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: K590||Constipation,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Linaclotide Capsule
Linaclotide 72 mcg once daily. If response (average SBM rate ≥3/week and an
increase of ≥1 from baseline for 3 of the first 4 weeks of the treatment period) is not
achieved in first 4 weeks, increase dose to 145 mcg once daily.
Comparator Agent
Matching Placebo of Linaclotide Capsule
Matching Placebo 72 mcg once daily. If response (average SBM rate ≥3/week and an increase of ≥1 from baseline for 3 of the first 4 weeks of the treatment period) is not achieved in first 4 weeks, increase dose to 145 mcg once daily.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or female patients of 18-65 years age
2. Ambulatory patients with chronic constipation (Fulfilling Rome IV criteria) reporting less than 3 Spontaneous
Bowel Movements (SBM) per week and reports one or more of the following symptoms for the last 3 months with symptom onset at least 6 months before the Screening Visit or before starting chronic therapy with any laxative:
ï‚· Straining during more than 25% of defecations
ï‚· Lumpy or hard stools more than 25% of defecations
ï‚· Sensation of incomplete evacuation more than 25% of defecations
3. Patients with less than 3 CSBM per week during pretreatment period.
4. Willing to comply with protocol requirements and sign a statement of informed consent
5. Willing to discontinue any laxatives used before the Pretreatment period in favor of the protocol-defined Rescue Medicine (bisacodyl Capsules or suppositories)
6. Agreed to refrain from making any new, major lifestyle changes that may have affected CIC symptoms (e.g., starting a new diet or changing his or her exercise pattern) from the time of signature of the ICF to the last trial visit.
7. Female subjects of child-bearing potential should have negative serum pregnancy test at screening and agree to use adequate birth control during the entire study period.
OR
Is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy has been performed on the study subject).
OR
Postmenopausal for at least 1 year
ExclusionCriteria
Details
1. Pregnant, breast feeding, or planning a pregnancy
2. Subject of any age with evidence of clinically significant weight loss, or rectal bleeding and without documentation of the results of either a flexible sigmoidoscopy or colonoscopy performed within 2-years period prior to screening.
3. Reports loose (mushy) or watery stools in the absence of any laxative intake in the form of a Capsule, a suppository or an enema, or prohibited medicine for greater than 25% of bowel movements
4. Reported a Bristol Stool Form Scale score of 6 (loose, mushy stools) for greater than 1 SBM or a Bristol Stool Form Scale score of 7 (watery stools) with any SBM over the 2 weeks pretreatment period before the Randomization Visit [Refer to appendix 3 for BSFS scale].
5. Received a diagnosis of inflammatory bowel disease (IBD)
6. Meet the Rome IV criteria for Irritable Bowel Syndrome (IBS) or the Rome IV criteria for Opioid-Induced Constipation (OIC).
7. Has a history of structural abnormality of the Gastrointestinal (GI) tract or a disease or condition that can affect GI motility
8. Has a history of diverticulitis, chronic pancreatitis, active peptic ulcer disease (PUD) not adequately treated, ischaemic colitis, inflammatory bowel disease, laxative abuse, faecal impaction that required hospitalization or emergency treatment, pseudo-obstruction, mega colon, mega rectum, bowel obstruction, descending perineum syndrome, ovarian cysts, endometriosis, solitary rectal ulcer syndrome, systemic sclerosis, pre-malignant colonic disease (e.g., familial adenomatous polyposis or hereditary non-polyposis colorectal cancer) or other forms of familial colorectal cancer.
9. Diagnosis or family history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or any other form of familial colorectal cancer
10. Current active peptic ulcer disease (i.e., disease that was not adequately treated or stable with therapy)
11. Has unexplained and clinically significant GI alarm signals (e.g., lower GI bleeding or heme-positive stool in the absence of known internal or external haemorrhoids, iron-deficiency anaemia, unexplained weight loss) or systemic signs of infection or colitis.
12. Patients who require chronic diuretic treatment
13. Has clinically significant laboratory findings or medical condition that could potentially affect study participation and/or personal well-being, as judged by the investigator.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Change from baseline to week 12 of Complete Spontaneous Bowel Movement (CSBM).
12 Weeks
Secondary Outcome
Outcome
TimePoints
1. Change from baseline in 12 week CSBM frequency rate
2. Change in weekly SBM frequency rate from baseline
3. Change in stool consistency score
4. Change in straining score
5. Change in abdominal bloating
6. Change in abdominal discomfort
12 Weeks
Target Sample Size
Total Sample Size="316" Sample Size from India="316" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Constipation is used to describe symptoms that relate
to difficulties in defecation. Chronic constipation is generally defined by
symptoms that persist for at least 3 months. Chronic
constipation (CC) is a highly prevalent condition affecting between 12% to 19% of the population. Laxatives are being commonly prescribed for the management of
chronic constipation.However, concerns such as inadequate response,
persistence of symptoms, adverse effects remain some important challenges with
the available treatment options. Further, patients with CC suffer
from a range of bowel symptoms of varying severities, may require
individualized approaches to the management of their symptoms, may differ in
their responsiveness to various treatments.
Linaclotide
is an already approved drug by USFDA since 2012 for patients with chronic
constipation and irritable bowel syndrome.Linaclotide is structurally related to human guanylin
and uroguanylin and functions as a guanylate cyclase-C (GC-C) agonist.
This
clinical trial is a prospective, multicenter, randomized, double-blind,
parallel-group, placebo-controlled study which will be conducted to evaluate
the efficacy, and safety of Linaclotide in patients with chronic constipation.
The trial consists of up to 28 days of screening (including 14 days of
pre-treatment period), and 12 weeks of double-blind treatment.
In the clinical trials, Linaclotide showed a favourable safety and
efficacy profile w.r.tstool consistency, straining,
constipation severity, abdominal discomfort, and bloating which may
prove to be beneficial for the patients with Chronic constipation. This study
is being conducted to generate the data regarding the efficacy and safety of
Linaclotide in Indian population. An unmet need for drugs exists despite the
availability of different treatment options for constipation.