Evaluation of Clinical Equivalence Between Two Lubiprostone Products in the Treatment of Chronic Idiopathic Constipation

A,Randomized , Double-blind,Double -Dummy Placebo-controlled,Parallel -Group, Multicenter Study to Evaluate the Clinical Equivalence of Lubiprostone 24 mcg Capsules ( Dr. Reddy's Laboratories Ltd.) With AMITIZA® (Lubiprostone ) 24 mcg Capsules ( Sucampo Pharmaceuticals, Inc. ) in the Treatment of Chronic Idiopathic Constipation

The objective of this study is to evaluate the clinical equivalence and safety of the test formulation of Lubiprostone 24 mcg capsules manufactured by Dr Reddy's Laboratories Ltd compared to the marketed formulation AMITIZA® ( Lubiprostone) 24 mcg capsules (Sucampo Pharmaceuticals, Inc.) in patients with confirmed Chronic Idiopathic Constipation

Study Overview

• Status: Completed
• Conditions: Chronic Idiopathic Constipation
• Intervention / Treatment: Drug: Lubiprostone; Drug: Lubiprostone; Drug: Placebo

Detailed Description

Constipation is a common gastrointestinal problem estimated to effect 2-27 % of the population in United States . It is found more commonly in women and elderly . The prevelance of constipation and growing demand for treatment dictate the need for safe and effective treatment options . Lubiprostone is the first chloride channel activator approved by FDA for long term treatment of chronic idiopathic constipation in adult men and women . To provide a generic medicine to the U.S population Dr Reddy's Laboratories intends to conduct this study to evaluate that the Lubiprostone manufactured by it is equally effective and safe as marketed AMITIZA® ( Lubiprostone) 24 mcg capsules (Sucampo Pharmaceuticals, Inc.)

• Study Type: Interventional
• Enrollment (Actual): 909
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Radiant Research
    • Dothan, Alabama, United States, 36305
      • Digestive Health Specialists of the Southeast
    • Huntsville, Alabama, United States, 35801
      • Clinical Research Associates
    • Mobile, Alabama, United States, 36608
      • Drug Research Group, LLC
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Radiant Research
    • Tucson, Arizona, United States, 85712
      • Visions Clinical Research
    • Tucson, Arizona, United States, 85712
      • Adobe Clinical Research , LLC
    • Tucson, Arizona, United States, 85741
      • SC Clinical Research, Inc
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Encinitas, California, United States, 92024
      • Diagnamics Inc,477 N. El Camino Real,Suite A100
    • Fresno, California, United States, 93710
      • Advanced Medical Research Institute
    • Fresno, California, United States, 93726
      • Research Center of Fresno
    • North Hollywood, California, United States, 91606
      • Translational Research Group
    • Northridge, California, United States, v
      • Staywell Research
    • Orange, California, United States, 92868
      • Elias Research Associates
    • Sacramento, California, United States, 95816
      • Benchmark Research
    • San Diego, California, United States, 92108
      • Medical Center for CR
    • San Francisco, California, United States
      • Shawn K Hassler
    • Upland, California, United States, 91786
      • SC Clinical Research, Inc ,1060 E. Foothill Blvd, Suite 204
    • Vista, California, United States, 92084
      • Progressive Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80239
      • Radiant Research
    • Denver, Colorado, United States, 80220
      • Horizons Clinical Research Center
    • Denver, Colorado, United States, 80246
      • Lynn Institute of Denver
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Consultants of Clinical
    • Brandon, Florida, United States, 33511
      • PAB Clinical Research
    • Clearwater, Florida, United States, 33761
      • Elite Trials
    • Hialeah, Florida, United States, 33012
      • Medical Research Unlimited, Llc
    • Hialeah, Florida, United States, 33012
      • Health Care Family Rehabilitation and Research Center
    • Jupiter, Florida, United States, 33458
      • Health Awareness ,Inc
    • Lauderdale Lakes, Florida, United States, 33319
      • Sunrise Medical Research
    • Miami, Florida, United States, 33126
      • Pharmax Research Clinic
    • Miami, Florida, United States, 33015
      • San Marcus Research Clinic
    • Miami, Florida, United States, 33155
      • Community Research Foundation , Inc.
    • Miami, Florida, United States, 33166
      • Florida International Research
    • Miami, Florida, United States, 33174
      • Columbus Clinical Services
    • Miami, Florida, United States, 33186
      • South Medical Research Group , Inc
    • Naples, Florida, United States, 34109
      • Pharma Research International, Inc
    • Naples, Florida, United States, 34110
      • Pharma Research International, Inc
    • Orlando, Florida, United States, 32806
      • Compass Research
    • Ormond, Florida, United States, 32174
      • Ormond Medical Arts Pharmaceutical
    • Plant City, Florida, United States, 33563
      • Clinical Research of Central Florida
    • Port Orange, Florida, United States, 32129
      • Accord Clinical Research,LLC
    • Saint Petersburg, Florida, United States, 33709
      • Meridian Research
    • Tampa, Florida, United States, 33606
      • Meridian Research
    • Winter Haven, Florida, United States, 33880
      • Clinical Research of Central Florida
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Mount Vernon Clinical Research
    • Atlanta, Georgia, United States, 30342
      • Gastroenterology Consultants PC
    • Marietta, Georgia, United States, 30067
      • Atlanta Gastroenterology Assoc
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
    • Stockbridge, Georgia, United States, 30281
      • Advanced Digestive Care Center , PC
  • Kansas
    • Newton, Kansas, United States, 67114
      • Heartland Research Associates
    • Wichita, Kansas, United States, 67205
      • Heartland Research Associates
  • Kentucky
    • Owensboro, Kentucky, United States, 42303
      • Research Integrity
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • East Jefferson Gastro
  • Massachusetts
    • Boston, Massachusetts, United States, 2131
      • Boston Clinical Trials Inc
    • Brockton, Massachusetts, United States, 02301
      • Beacon Clinical Research
    • Watertown, Massachusetts, United States, 2472
      • Bay State Clinical Trials, Inc.
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute
    • Kalamazoo, Michigan, United States, 49009
      • Bayer Research
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • GI Associates and Endoscopy Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research, Inc
  • New Jersey
    • Elizabeth, New Jersey, United States, 07202
      • Central Jersey Medical Research Center
    • Newark, New Jersey, United States, 07103
      • University Hospital,150 Bergen Street,B-134 Pharmacy
  • New York
    • Brooklyn, New York, United States, 11206
      • Hosc Inc.
    • Hollis, New York, United States, 11423
      • NY Scientific,189-11 Jamaica Ave
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Peters Medical Research
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
    • Salisbury, North Carolina, United States, 28144
      • PMG Research of Salisbury
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem, LLC
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Valley Medical Research
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research , Inc
    • Columbus, Ohio, United States, 43212
      • Radiant Research
    • Mentor, Ohio, United States, 44060
      • Great Lakes Gastroenterology
  • Pennsylvania
    • Lansdale, Pennsylvania, United States, 19446
      • Detweiler Family Medicine and Associates, PC
    • Pittsburgh, Pennsylvania, United States, 15206
      • Clinical Trials Research Services, LLC
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Radiant Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • ClinSearch LLC
    • Jackson, Tennessee, United States, 38305
      • HCCA-CRS
  • Texas
    • Dallas, Texas, United States, 75230
      • KRK Medical Research
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77034
      • Gastroenterology Consultants P.A
    • Pasadena, Texas, United States, 77505
      • Digestive Health Center
    • San Antonio, Texas, United States, 78215
      • Sun Research
    • San Antonio, Texas, United States, 78205
      • Paragon Research Center
    • San Antonio, Texas, United States, 78209
      • Quality Research, Inc
    • San Antonio, Texas, United States, 78238
      • Texas Medical Research Associates , LLC
    • Sugarland, Texas, United States, 77479
      • Breco Research
    • Sugarland, Texas, United States, 77479
      • Pioneer Research Solutions , Inc
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research Center
    • Lynchburg, Virginia, United States, 24502
      • BlueRidge Medical Research
    • Newport news, Virginia, United States, 23606
      • Health Research of Hampton Roads

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

1. Patients who have signed the written informed consent form prior to entering the study.
2. Male or non-pregnant female aged ≥ 18 years with a clinical diagnosis of CIC defined as, on average, < 3 SBMs per week and confirmed by daily diary during the two week baseline/washout period. An SBM is defined as any bowel movement (BM) that does not occur within 24 hours after rescue medication use.
3. Patients with body mass index between 18 and 35kg/m2 (both inclusive)

4. Have one or more of the following symptoms related to BMs for at least 6 months before the baseline visit and confirmed by daily diary during the 2 weeks baseline/washout period:

   i. very hard (little balls) and/or hard stools for at least 25% of the bowel movements ii. sensation of incomplete evacuation following at least 25% of the bowel movements iii. straining at defecation at least a quarter of the time

5. Women of child-bearing potential should have a negative serum pregnancy test prior to beginning therapy and agree to use effective contraceptive methods (at least one medically approved and highly effective method of birth control defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, oral contraceptives combined with at least one barrier method, hormonal IUDs, sexual abstinence or vasectomy of the partner) during the study.
6. For patients aged < 50 years, documentation of the results of either a flexible sigmoidoscopy or colonoscopy performed within the five years prior to dosing, showing no mechanical bowel obstruction or organic disorders of the large or small bowel.
7. For patients aged ≥ 50 years, documentation of the results of either a barium enema with flexible sigmoidoscopy or colonoscopy performed within one year prior to dosing, showing no mechanical bowel obstruction or organic disorders of the large or small bowel.

Main Exclusion Criteria:

1. Females who are pregnant, breast feeding, or planning a pregnancy during the proposed study period.
2. Patients of any age with evidence of weight loss, anemia, or rectal bleeding and without documentation of the results of either a flexible sigmoidoscopy or colonoscopy performed during the 6 months prior to dosing.
3. Patients who have documented mechanical bowel obstruction (e.g., bowel obstruction due to tumor, hernia), megacolon/megarectum, or diagnosis of pseudo-obstruction.
4. Patients with known or suspected organic disorders of the large or small bowel (e.g., inflammatory bowel disease, ulcerative colitis, Crohn's Disease) or constipation secondary to a documented cause (e.g., surgery, bowel resection) or acute hernia or with neurologic diseases or other diseases that cause motility problems for example Parkinson's disease and spinal cord injury, etc.
5. Patients with a history of bowel resection.
6. Patients who are regularly using medications, which are known to cause constipation (anticholinergics, narcotics, calcium channel blockers, tricyclic antidepressants, colchicine, iron supplements, magnesium supplements).
7. Patients who are hospitalized for any gastrointestinal or abdominal surgical procedure during the three months prior to dosing.
8. Patients with clinically significant cardiovascular, liver, lung, neurologic, renal or psychiatric disorder, or clinically significant laboratory abnormalities (if laboratory values exceed 2X Upper Limit of Normal the approval of medical monitor should be taken into consideration before randomizing the patient).
9. Use of systemic antibiotics within four weeks prior to baseline.
10. Any current or planned significant change in diet during the study.
11. Participation in a study with any investigational medication within the past 30 days before screening for this study or previous participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lubiprostone; Manufactured by Dr Reddy's Laboratories Ltd( 24 mcg administered for 7 days )	Drug: Lubiprostone; 24 mcg Capsules to be given in the experimental arm with Placebo Of AMITIZA; Drug: Lubiprostone; 24 mcg Capsules with placebo of Lubiprostone ( Manufactured by Dr Reddy's Laboratories Ltd)
Active Comparator: AMITIZA®; Manufactured by Sucampo Pharmaceuticals(24 mcg administered for 7 days)	Drug: Lubiprostone; 24 mcg Capsules to be given in the experimental arm with Placebo Of AMITIZA; Drug: Lubiprostone; 24 mcg Capsules with placebo of Lubiprostone ( Manufactured by Dr Reddy's Laboratories Ltd)
Placebo Comparator: Placebo; Manufactured by Dr Reddy's Laboratories Ltd ( 24 mcg adminstered for 7 days )	Drug: Placebo; 24 mcg capsules of both experimental Lubiprostone and AMITIZA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Analysis	Clinical equivalence of the Test and Reference treatments and the superiority of each active treatment over the Placebo in the change from baseline in mean number of SBM's during the 7 day treatment period of the study	Day 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Analysis	The type , frequency and severity of adverse events across the treatment groups will be analyzed at the end of the study	Day 8

Collaborators and Investigators

• Sponsor: Dr. Reddy's Laboratories Limited
• Collaborators: Parexel
• Investigators: Study Director: Ashis Patnaik, M.D, Dr. Reddy's Laboratories Limited; Study Director: Shilpi Dhawan, M.D, Dr. Reddy's Laboratories Limited

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: August 21, 2012
• First Submitted That Met QC Criteria: August 24, 2012
• First Posted (Estimate): August 29, 2012

Study Record Updates

• Last Update Posted (Estimate): April 3, 2014
• Last Update Submitted That Met QC Criteria: April 2, 2014
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Lubiprostone
• Other Study ID Numbers: DRL-USG01-L/2012