Effect of elobixibat Tablets 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 elobixibat once daily of Dr. Reddy’s laboratories limited in patients with chronic constipation
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
DRL-IND-NDA03-ELO/2022; Version 1.0 Dated 11 March 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Piyush Agarwal
Designation
Head - Clinical Development & Clinical Strategy
Affiliation
Dr. Reddy’s Laboratories Limited
Address
Global Clinical Management, IPDO, Innovation plaza, Bachupally
village, Bachupally Mandal, Hyderabad, Medchal Malkajgiri District
Medchal
TELANGANA
500090
India
Medchal TELANGANA 500090 India
Phone
Fax
Email
piyushagarwal@drreddys.com
Details of Contact Person Scientific Query
Name
Dr Shradhanand Singh
Designation
Lead - Clinical and Medical Operations and Strategy
Affiliation
Dr. Reddy’s Laboratories Limited
Address
Global Clinical Management, IPDO, Innovation plaza, Bachupally
village, Bachupally Mandal, Hyderabad, Medchal Malkajgiri District
Medchal
TELANGANA
500090
India
Medchal TELANGANA 500090 India
Phone
Fax
Email
shradhanandsingh@drreddys.com
Details of Contact Person Public Query
Name
Vipul Modh
Designation
Specialist-Clinical and Medical Operations
Affiliation
Dr. Reddy’s Laboratories Limited
Address
Global Clinical Management, IPDO, Innovation plaza, Bachupally
village, Bachupally Mandal, Hyderabad, Medchal Malkajgiri District
Medchal
TELANGANA
500090
India
Medchal TELANGANA 500090 India
Phone
Fax
Email
vipulmodh@drreddys.com
Source of Monetary or Material Support
Dr. Reddys Laboratories Limited, Integrated Product Development, Innovation Plaza, Survey No
42, 45 & 46, Bachupally Village, Bachupally Mandal, Medchal Malkajgiri District, Hyderabad 500
090, Telangana, India
Primary Sponsor
Name
Dr Reddys Laboratories Limited
Address
IPDO, Innovation plaza, Bachupally village, Bachupally Mandal,
Hyderabad, Medchal Malkajgiri District, 500090, Telangana, India
Department of Gasteronenterolgy, Dayanand Medical College and Hospital, Civil lines, Tagore Nagar, Ludhiana, Punjab - 141001 Ludhiana PUNJAB
9914821155
goyalomesh@yahoo.co.in
Dr Ujwal Gajula
Excel Hospital, Secunderabad
Excel Hospital, # 1-5-56/29, Old Alwal, Near IG Statue, Alwal, Secunderabad – 500010, Telangana, India Hyderabad TELANGANA
9604300648
drujjwal95@gmail.com
Dr Abhijit Chandra
Gandhi Memorial and associated Hospitals, King George’s Medical University, Lucknow
Department of Surgical Gastroenterology, Gandhi Memorial and associated Hospitals, King George’s Medical University, (U.P), Lucknow-226003 (U.P) India Lucknow UTTAR PRADESH
9335920302
abhijitchandra@hotmail.com
Dr Ravindra Gaadhe
Gastroplus Digestive Disease Centre, Ahmedabad
Gastroplus Digestive Disease Centre, D-Block, 3rd Floor, Galaxy Bazaar, Sunrise Park Road, Vastrapur, Ahmedabad-380054, Gujarat Ahmadabad GUJARAT
9276558517
ravindragaadhe@gmail.com
Dr K N Chandan Kumar
Gleneagles Global Hospitals, Hyderabad
Gleneagles Global Hospitals, Lakdikapool,
Hyderabad – 500004,
Telangana Hyderabad TELANGANA
8754919777
drchandankn@gmail.com
Dr Anumula Kavitha
Government General Hospital and Guntur Medical College, Guntur
Department of Gastroenterology, Government General Hospital,
Jubilee Block, Guntur - 522001
Andhra Pradesh, India. Guntur ANDHRA PRADESH
9399977555
jananigastro@ymail.com
Dr Vinay Kumar
GSVM Medical College Kanpur
Post Graduate Department of
Medicine, GSVM
Medical college,
Swaroop Nagar, Kanpur
– 208002, Uttar
Pradesh
Kanpur Nagar
UTTAR PRADESH Kanpur Nagar UTTAR PRADESH
S.R. Kalla Memorial Gastro and General Hospital, Jaipur
S.R. Kalla Memorial Gastro and General Hospital, 78-79, Dhuleshwar Garden, Behind HSBC Bank , Sardar Patel Marg, C – scheme, Jaipur – 302001, Rajasthan Jaipur RAJASTHAN
9829050622
drmkalla@rediffmail.com
Dr Kabrawala Mayank Vasantlal
Surat Institute of Digestive sciences, Surat
Surat Institute of Digestive sciences, A unit of SIDS Healthcare Pvt. Ltd., Vijay Nagar Gate No-3, Besides Nirman bhavan, Opposite Gandhi College, Majura Gate, Rind road, Surat-395002, Gujarat Surat GUJARAT
9825130363
mayankkabrawala@hotmail.com
Dr B Ravi Shankar
Yashoda Hospitals, Hyderabad
Department of Medical Gastroenterology, Yashoda Hospitals, Behind Hari Hara Kala Bhavan, SP Road, Secunderabad-500003, Telangana, India. Hyderabad TELANGANA
SR Kalla Memorial Ethical Committee For Human Research, Jaipur
Approved
Surat Institute of Digestive Sciences Ethics Committee, Surat
Approved
Yashoda Academy of Medical Education and Research Yashoda Hosptials, Hyderabad
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
Elobixibat tablet
Elobixibat tablet (10 mg once daily as two tablets of 5 mg) before Breakfast for 2 weeks
Comparator Agent
Matching placebo of Elobixibat Tablet
Matching placebo of Elobixibat tablet (10 mg once daily orally as two tablets of 5 mg) before Breakfast for 2 weeks
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 <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:
- Straining during more than 25% of defecations
- Lumpy or hard stools more than 25% of defecations
- Sensation of incomplete evacuation more than 25% of defecations
3. Patients with less than 3 SBM 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 tablets or suppositories)
6. Agreed to refrain from making any new, major life-style 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 (acceptable methods include intrauterine device, barrier or abstinence).
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, anemia, 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 tablet, a suppository or an enema, or prohibited medicine for >25% of bowel movements.
4. Reported a Bristol Stool Form Scale score of 6 (loose, mushy stools) for > 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.
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. Has a potential central nervous system (CNS) cause of constipation
13. Has intestinal/rectal prolapse or other known pelvic floor dysfunction
14. Commonly uses digital maneuvers (perianal pressure or digital disimpaction) or vaginal splinting to facilitate the passage of a bowel movement
15. Has a history of diabetic neuropathy
16. Bariatric surgery for treatment of obesity, or surgery to remove a segment of the GI tract at any time before the Screening Visit, surgery of the abdomen, pelvis, or retroperitoneal structures during the 6 months before the Screening Visit, an appendectomy or cholecystectomy during the 60 days before the Screening Visit, other major surgery during the 30 days before the Screening Visit.
17. Has a history of cancer with last date of proven disease activity/presence of malignancy within 5 years, except for adequately treated basal cell carcinoma of the skin, cervical dysplasia, or carcinoma in situ of the skin or the cervix
18. Known human immunodeficiency virus (HIV) or Hepatitis B/C (HBV/HCV) infection
19. Has a history of hospitalization for any psychiatric disorder, or any suicide attempt in the 2 years prior to Screening
20. History of alcohol or drug abuse during the 6 months prior to Screening
21. Reported using a Prohibited Medicine (excluding laxatives, suppositories, and enemas) during the Pretreatment Period or was not willing or able to abide by the restrictions regarding use of Prohibited Medicines (Note: The use of fiber, bulk laxatives, or stool softeners [such as docusate] was acceptable provided the patient had been on a stable dose during the 30 days before the Screening Visit and planned to continue on a stable dose throughout the trial).
22. Patients having following lab parameters deranged defined as follows:
-Renal function: Serum Creatinine ≥1.5 × upper limit of normal (ULN)
- Hepatic function: AST and ALT ≥3 × ULN;
- Hemoglobin: < 8g/dL
23. Has a clinically significant laboratory finding 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 in weekly frequency of Spontaneous Bowel Movement (SBM)
Week 1 And Week 2
Secondary Outcome
Outcome
TimePoints
Proportion of patients with complete spontaneous bowel movement (CSBM)
Week 1 And Week 2
Proportion of patients with a Spontaneous Bowel Movement within 24 h after the first dose of study drug
With in 24 hour
Median time to first Spontaneous Bowel Movement
First timepoint to Spontaneous Bowel Movement
Change from baseline in Stool consistency using Bristol Stool Form Scale
Week 1 and week 2
Change from Baseline in Weekly Degree of Straining of Spontaneous Bowel Movement
Week 1 And Week 2
Change from Baseline in Weekly Abdominal Bloating Score
Week 1 And Week 2
Change from Baseline in Weekly Abdominal Discomfort Score
Week 1 And Week 2
Target Sample Size
Total Sample Size="150" Sample Size from India="150" 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
This study is planned to evaluate the efficacy, and safety of Elobixibat tablet (10 mg oral once daily administered as two tablets of 5 mg) in patients with chronic constipation. Male and non-pregnant female subjects (18-65 years of age) with clinical diagnosis of chronic constipation will be included in the trial.