Clinical Bioequivalence study of Linaclotide 145 mcg capsule in patients with constipation.
Scientific Title of Study
A Randomized, Double-blinded, Parallel, Placebo-controlled, Multicenter, bioequivalence study with clinical endpoint to assess efficacy and safety of Linaclotide 145 mcg capsule (manufactured by Arab Pharmaceutical Manufacturing PSC, Jordan for Hikma Pharmaceuticals (MAH)) to LINZESS® (linaclotide) 145 mcg capsules (Allergan USA, Inc. Madison, NJ 07940) in the treatment of chronic idiopathic constipation.
Trial Acronym
22-VIN-0003
Secondary IDs if Any
Secondary ID
Identifier
22-VIN-0003 Version 01 dated 24 Nov 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Sivakumar Vaidyanathan
Designation
Head - Clinical Trials
Affiliation
Veeda Clinical Research Ltd
Address
Veeda Clinical Research Ltd., Shivalik Plaza, Near I.I.M., Ambawadi,
Ahmedabad – 380 015, Gujarat, India
Ahmadabad GUJARAT 380 015 India
Phone
9167977840
Fax
Email
sivakumar.vaidyanathan@veedacr.com
Details of Contact Person Scientific Query
Name
Dr Ravi Alamchandani
Designation
General Manager
Affiliation
Veeda Clinical Research Ltd
Address
Veeda Clinical Research Ltd., Shivalik Plaza, Near I.I.M., Ambawadi,
Ahmedabad – 380 015, Gujarat, India
Ahmadabad GUJARAT 380 015 India
Phone
9687306158
Fax
Email
Ravi.A1950@veedacr.com
Details of Contact Person Public Query
Name
Dr Ravi Alamchandani
Designation
General Manager
Affiliation
Veeda Clinical Research Ltd
Address
Veeda Clinical Research Ltd., Shivalik Plaza, Near I.I.M., Ambawadi,
Ahmedabad – 380 015, Gujarat, India
Ahmadabad GUJARAT 380 015 India
Phone
9687306158
Fax
Email
Ravi.A1950@veedacr.com
Source of Monetary or Material Support
Hikma Pharmaceuticals LLC, 21 Saleem Bin All-Hareth street
Industrial Area, Bayader Wadi Al-Seer
P.O. Box 182400
11118 Amman-Jordan
Primary Sponsor
Name
Hikma Pharmaceuticals LLC
Address
21 Saleem Bin All-Hareth street
Industrial Area, Bayader Wadi Al-Seer
P.O. Box 182400
11118 Amman-Jordan
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Veeda Clinical Research Ltd
Shivalik Plaza, Near I.I.M.,
Ambawadi, Ahmedabad – 380 015, India
Clinical Research Room, Survey no:32/2, Near Abhishek Hotel,Gulwani Maharaj
Road, Erandwane, Pune, Maharashtra- 411004 Pune MAHARASHTRA
9021133704
drnachi@yahoo.co.in
Dr Vikas Bundela
Adhar Health Institute
Department of clinical
research, Room no.
NA,Nr South Bypass
Crossing, NH-10,
Tosham Road
Connection-125005. Hisar HARYANA
8427483115
vkb.923@gmail.com
Dr Rakesh Patel
Ashirwad Hospital and Research Center
Clinical research
Department, 3rd Floor,
Ashirwad Hospital &
Research center,
Maratha Section, Near
Jijamata udhyan,
Ullhasnagar 421004
Thane MAHARASHTRA
Room no 5, third floor,
cancer building,
Lokmanya Hospital,
314/B Telco road,
Chinchwad, Pune
411033 Pune MAHARASHTRA
9920039265
prasadbhate07@gmail.com
Dr Dhaval Gupta
Medilink Hospital Research Centre
1st floor medilink Hospital near Shyamal crossroad 132 ft. ring road satellite 380015
Ahmadabad GUJARAT
9979979352
drdhavalgupta@gmail.com
Dr Dharmendra B L
Mysore Medical College and Research Institute
Clinical Research Room, Next to NSB 12th 2nd floor, new surgical block , Irwin road,
Mysore 570001 Mysore KARNATAKA
9844400382
drdharmu21@gmail.com
Dr Hitesh Patel
Phoenix Hospital
2nd & 3rd floor, 239-252 and 323-325, city center arcade, below apple hospital, near SRP campus, Naroda patiya, Naroda highway, Krushnanagar, 382330 Ahmadabad GUJARAT
9909019925
dr.hitspatel@gmail.com
Dr Krishna Kant Rawal
Prime Institute of Institute of digestive science
Athithi chowk, Near chandresswadi, Panchwati society, Main road, Rajkot- 360001 Rajkot GUJARAT
9824212169
kkrawal@gmail.com
Dr Vipul Chavda
Rudraksh Hospital
1st Floor, Rajmandir Complex, off to Bareja fly over, Bareja-382425
Ahmadabad GUJARAT
9909979236
drvpchavda@gmail.com
Dr Chirag Shah
Sai Krupa Research Centre
Sai Krupa Hospital, F-30-31 Satyam Status, Opp. Chandan Party plot, Anandnagar ramdev nagar road, Sattelite. Ahmedabad 380053 Ahmadabad GUJARAT
7567159591
drchirag2606@gmail.com
Dr Rupal Doshi
SSG Hospital Government Medical College
Clinical study room ,
2nd floor new emergency building, sir sayaji rao general hospital, medical college, baroda, Jail road, vadodara 390001 Vadodara GUJARAT
9824083734
rupal265@yahoo.com
Dr Mahesh Mangulkar
Supe Heart & Diabetec hospital and research center
2nd floor, room no : 12,
Supe Heart & Diabetes
Hospital & Research
centre, Opp Adhar
Ashram, near Rungtha
high school, Gharpure
ghat, Ashok stambh,
Panchvati, Nashik
422002 Nashik MAHARASHTRA
8087537224
drmaheshmangulkar22@gmail.com
Dr Dhaiwat Shukla
V.S General Hospital
Room No 239 Emergency Trauma Building Ellisbridge Paldi,
Ahmedabad- 380006 Ahmadabad GUJARAT
Bhaktivedanta Hospital and Research institute, Mumbai
Approved
Ethics Committee of Ishwar Institute of HealthCare, Aurangabad
Approved
Gastro Plus Ethics Committee
Approved
IEC-MMC and RI and Associated Hospital Mysore Medical College and Research Institute, Mysore
Approved
Institutional Ethics Committee - ACE HOSPITAL - Dr. Nachiket
Approved
INSTITUTIONAL ETHICS COMMITTEE for Human research Medical College
Submittted/Under Review
INSTITUTIONAL ETHICS COMMITTEE for Human research Medical College
Submittted/Under Review
Institutional Ethics Committee lokmanya medical research center, Pune
Approved
Medilink ethics committee, Ahmedabad
Approved
Parth Hospital Institutional Ethics Committee
Approved
Prime Hospital Institutional Ethics Committee
Approved
Rudraksha Hospital Ethics Committee Gujarat
Approved
Sangini Hospital Ethics Committee
Approved
Shrey Hospital Institutional Ethics Committee
Approved
Supe Hospital Ethics Committee, Nashik
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 145 mcg capsules
145 mg To be taken orally 30 minutes before the first meal of the day, Once a day Manufactured by: Arab Pharmaceutical Manufacturing PSC, Jordan for Hikma Pharmaceuticals (MAH).
Treatment period 7 + 2 days
Comparator Agent
LINZESS® (linaclotide) 145 mcg capsules
Once a daily 145 mg capsule (Manufactured by Allergan Inc, Madison, NJ 07940, USA) to be taken orally 30 minutes before the first meal of the day, for a treatment period at least 7 days.
Comparator Agent
Placebo
Once a daily 145 mg capsule (Manufactured by Arab Pharmaceutical Manufacturing PSC, Jordan for Hikma Pharmaceuticals) to be taken orally 30 minutes before the first meal of the day, for a treatment period at least 7 days.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Brief inclusion as below,
1. Male or female more than and equal to 18 years with a clinical diagnosis of chronic idiopathic constipation (CIC).
2. Ability to provide written informed consent for the study.
3. Have 1 or more of the following symptoms related to bowel movements:
• Lumpy or hard stools for more than 25% of the bowel movements
• Sensation of incomplete evacuation following more than 25% of the bowel movements.
• Straining at defecation more than 25% of the time.
4. Meet the colonoscopy requirements defined by the American Gastroenterological Association (AGA) guidelines.
5. Willing to discontinue any laxatives used before the Pretreatment Visit in favor of the protocol-defined Rescue Medicine.
6. Agree to refrain from making any new major lifestyle changes that may have affected CIC symptoms from the time of screening to the last trial visit.
7. Free from any clinically significant disease.
8. Comply with protocol & Investigator visit requirements.
ExclusionCriteria
Details
1. Pregnant, breastfeeding, or planning a pregnancy.
2. Subject with evidence of weight loss, anemia, or rectal bleeding or documented colonoscopy performed during the 6 months prior to dosing.
3. Documented mechanical bowel obstruction, megacolon/megarectum, or diagnosis of pseudo-obstruction.
4. GI track Structural abnormality or a disease or condition that could affect GI motility
5. Fecal impaction that required hospitalization or emergency room treatment, or had a history of cathartic colon, laxative or enema abuse, ischemic colitis, or pelvic floor dysfunction.
6. Meet the Rome IV criteria for Irritable Bowel Syndrome or Opioid-Induced Constipation.
7. Diagnosis or family history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or any other form of familial colorectal cancer.
8. Current active peptic ulcer disease
9. History of diabetic neuropathy, diverticulitis or any chronic condition that could be associated with abdominal pain or discomfort
10. History of Bariatric surgery or surgery to remove a segment of the GI tract 6 months before the Screening Visit, major surgery within 4 weeks prior to study, an appendectomy or cholecystectomy during the 60 days before the Screening Visit, or other major surgery during the 30 days before the Screening Visit.
11. Potential central nervous system cause of constipation
12. Untreated hypothyroidism or treated hypothyroidism for which the dose of thyroid hormone had not been stable for at least 6 weeks at the time of the Screening Visit
13. Hospitalized for any gastrointestinal or abdominal surgical procedure during the 3 months prior to dosing.
14. Clinically significant cardiovascular, liver, lung, neurologic, renal or psychiatric disorder, or hematologic and/or biochemical abnormalities based on laboratory testing.
15. Used Rescue Medicine or any other laxative, suppository, or enema, on the calendar day before or the calendar day of the start of the Treatment Period.
16. Reported using a Prohibited Medicine during the Pretreatment Period or was not willing or able to abide by the restrictions regarding use of Prohibited Medicines
17. Any other conditions, including severe illness, which would make the patient, in the opinion of the Investigator, unsuitable for the study.
18. Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery.
19. Positive for drugs of abuse or Breath alcohol analyzer test prior to receiving the first dose/baseline of the investigational medicinal product in the study.
20. Patients found positive for HIV, Syphilis, Hepatitis B surface antigen or Hepatitis C antibody at screening.
21. Receipt of an investigational medicinal product or participation in another drug research study within 30 Days.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
• Primary Objective: To evaluate bioequivalence by establishing equivalence between Linaclotide 145 mcg capsule (Hikma Pharmaceuticals LLC, Jordan) to LINZESS® (linaclotide) 145 mcg capsules (Allergan USA) in the treatment of chronic idiopathic constipation.
•Primary Endpoint: Number of spontaneous bowel movement (SBM) during Week 1 (study Days 1-7), compared to baseline.
Note: An SBM is defined as any bowel movement that did not occur within 24 hours after rescue medication use.
Primary endpoint and secondary end point assessment will be done at Visit 4 (Day 4) and Visit 5 (1 weeks) for each study patient deemed eligible for evaluation
Secondary Outcome
Outcome
TimePoints
• Secondary Objective :To assess the safety and tolerability profile of the reference product & test product.
To demonstrate statistical superiority of both the Test and Reference products over Placebo in terms of clinical endpoint efficacy.
• secondary endpoints - No statistical calculations will be performed .
The proportion of patients with a SBM within 24 hours of receiving the first dose [ 24 hours after the first dose]
Time to first SBM after the first dose up to 1 week.
Change from baseline in 1-Week SBM frequency rate (SBMs/week)
Change from Baseline in 1-Week Stool Consistency Assessment (seven-point ordinal Bristol Stool Form Scale)
Secondary end point assessment will be done at Visit 4 (Day 4) and Visit 5 (1 weeks) for each study patient deemed eligible for evaluation
Target Sample Size
Total Sample Size="450" Sample Size from India="450" Final Enrollment numbers achieved (Total)= "450" Final Enrollment numbers achieved (India)="450"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This will be a randomized, double-blinded, parallel, placebo-controlled, multicenter, bioequivalence study with clinical endpoint to assess efficacy and safety of Linaclotide 145 mcg capsule (Hikma Pharmaceuticals LLC, Jordan) as compared to LINZESS® (linaclotide) 145 mcg capsules (Allergan USA, Inc. Madison, NJ 07940) in the treatment of chronic idiopathic constipation at multiple clinical trial sites in India.
Each study patient will self-administer one capsule of test, reference or placebo product orally once daily, for 1 week.
Primary endpoint and secondary end point(s) assessment will be done at Visit 4 (Day 4 ± 1 day)and Visit 5 (1 week +2 days) for each study patient deemed eligible for evaluation.
Total duration of study will be at least 35 +2 days including screening period of Max 14 days, pre-treatment period of Max 14 days and treatment period 7 + 2 days.