PREVENT1: Prevention of Recurrence of Diverticulitis

Sponsor
Shire (Industry)
Overall Status
Completed
CT.gov ID
NCT00545740
Collaborator
(none)
590
121
4
51.2
4.9
0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether SPD476 is effective in reducing recurrence of diverticulitis.

Condition or Disease Intervention/Treatment Phase
  • Drug: SPD476 (1.2g)
  • Drug: SPD476 (2.4 g)
  • Drug: SPD476 (4.8 g)
  • Drug: Placebo
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
590 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Phase III, Randomised, Double-Blind, Dose-Response, Stratified, Placebo-Controlled Study Evaluating the Safety and Efficacy of SPD476 Versus Placebo Over 104 Weeks in the Prevention of Recurrence of Diverticulitis.
Actual Study Start Date :
Nov 28, 2007
Actual Primary Completion Date :
Mar 5, 2012
Actual Study Completion Date :
Mar 5, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: SPD476 (1.2 g)

Drug: SPD476 (1.2g)
1.2g SPD476 once daily (QD) orally
Other Names:
  • Lialda, MMX™ mesalazine
  • Experimental: SPD476 (2.4 g)

    Drug: SPD476 (2.4 g)
    2.4g SPD476 QD orally
    Other Names:
  • Lialda, MMX™ mesalazine
  • Experimental: SPD476 (4.8 g)

    Drug: SPD476 (4.8 g)
    4.8g SPD476 QD orally
    Other Names:
  • Lialda, MMX™ mesalazine
  • Placebo Comparator: Placebo

    Drug: Placebo
    QD orally

    Outcome Measures

    Primary Outcome Measures

    1. Percent of Subjects Without Recurrence of Diverticulitis [Up to 104 weeks]

      Recurrence of diverticulitis is defined as the presence of each and all of the following 3 items: 1) abdominal pain, 2) a 15% increase in white blood cell count from baseline, 3) bowel wall thickening (>5 mm) and/or fat stranding as evidenced by spiral computerized axial tomography (CT) scan; OR surgical intervention for diverticular disease. Withdrawals are considered as recurrences.

    Secondary Outcome Measures

    1. Percent of Subjects Who Were CT-Recurrence Free of Diverticulitis [Up to 104 weeks]

      CT-recurrence of diverticulitis is defined as: a positive spiral CT scan for diverticulitis showing, at a minimum, fat stranding with or without bowel wall thickening >5 mm or surgical intervention for diverticular disease. Withdrawals considered as CT-recurrences.

    2. Number of CT Scans Performed Within 7 Days of Suspected Recurrence of Diverticulitis That Were Positive [Up to 104 weeks]

      A positive CT scan was defined as a CT scan that showed bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader.

    3. Number of CT Scans Performed Within 7 Days of Suspected Recurrence of Diverticulitis That Were Negative [Up to 104 weeks]

      A negative CT scan was defined as a CT scan that did not show bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader.

    4. Number of CT Scans Performed More Than 7 Days From Suspected Recurrence of Diverticulitis That Were Positive [Up to 104 weeks]

      A positive CT scan was defined as a CT scan that showed bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader.

    5. Number of CT Scans Performed More Than 7 Days From Suspected Recurrence of Diverticulitis That Were Negative [Up to 104 weeks]

      A negative CT scan was defined as a CT scan that did not show bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader.

    6. Percent of Subjects Requiring Surgery for Diverticulitis [Up to 104 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Males and females =>18yrs of age.

    2. If female of childbearing potential (FOCP), has demonstrated a negative beta HCG (human chorionic gonadotropin) serum pregnancy test, and agrees to comply with any applicable contraceptive requirements of the protocol.

    3. An episode of acute diverticulitis that resolved without colonic resection.

    4. Confirmation of diverticulosis via endoscopic evaluation of the sigmoid colon with at least three diverticula noted.

    Exclusion Criteria:
    1. Previous colorectal surgery, including surgical intervention for diverticular disease (with the exception of haemorrhoidectomy, colonic removal of polyps, and appendectomy)

    2. Active peptic ulcer disease

    3. History of or current presence of inflammatory bowel disease (IBD)

    4. Subjects with active irritable bowel syndrome (IBS) requiring ongoing medication

    5. Allergy or hypersensitivity to aspirin or related compounds

    6. Allergy to radiologic contrast agents

    7. Use of another Investigational product within 30 days of Baseline

    8. Use of antibiotic therapy within 4 weeks of Baseline

    9. Within 14 days of Baseline, use of prebiotic, probiotic or 5-ASA medications, as well as drugs active at the 5HT-receptor or anti-spasmodic agents

    10. Use of systemic or rectal steroids within 6 weeks of Baseline. Use of inhaled or nasal steroids is acceptable

    11. Use of anti-inflammatory drugs, (NSIADs, COX-2 inhibitors) including aspirin (except for cardiac prophylaxis) and ibuprofen, on a regular and ongoing basis

    12. History of alcohol or other substance abuse within the previous year

    13. Active or recent history of endometriosis or dysmenorrhoea within 6 months prior to Baseline

    14. Females who are lactating

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Dedicated Clinical Research Litchfield Park Arizona United States 85340
    2 Lynn Institute of the Ozarks Little Rock Arkansas United States 72205
    3 Advanced Clinical Research Institute Anaheim California United States 92108
    4 GW Research Chula Vista California United States 91910
    5 Monterey Bay GI Research Institute, Inc Monterey California United States 93940
    6 Rancho Cucamonga C. Trials Rancho Cucamonga California United States 91730
    7 Clinical Trials Research Roseville California United States 95661
    8 Medical Associates Research San Diego California United States 92123
    9 Torrance Clinical Research Torrance California United States 90505
    10 Rocky Mountain Gastroenterology Associates Thornton Colorado United States 80229
    11 Gastroenterology Associates of Fairfield County Bridgeport Connecticut United States 06606
    12 Yale Center for Clinical Investigation New Haven Connecticut United States 06520
    13 ZASA Clinical Research Boynton Beach Florida United States 33472
    14 Clinical Research of West Florida, Inc. Clearwater Florida United States 33765
    15 Borland-Groover Clinic Jacksonville Florida United States 32256
    16 Compass Research Orlando Florida United States 32806
    17 Accord Clinic Research, LLC Port Orange Florida United States 32129
    18 Florida Medical Clinic/Tampa Clinical Trials Tampa Florida United States 33613
    19 Gastroenterology Associates of Central Georgia, LLC Macon Georgia United States 31201
    20 Saint John's Research Institute Anderson Indiana United States 46016
    21 Digestive & Liver Disease Consultants Clive Iowa United States 50325
    22 New Orleans Research Institute Metairie Louisiana United States 70006
    23 Digestive Disease Associates Baltimore Maryland United States 21229
    24 Endoscopic Microsurgery Associates, PA Towson Maryland United States 21204
    25 Borgess Research Institute Kalamazoo Michigan United States 49048
    26 Jefferson City Medical Group Jefferson City Missouri United States 65109
    27 South Jersey Gastroenterology, P.A. Marlton New Jersey United States 08053
    28 Howard Guss, DO Ocean City New Jersey United States 07712
    29 New Jersey Physicians, LLC Passaic New Jersey United States 07055
    30 Allied Gastrointestinal Associates, P.A. Voorhees New Jersey United States 08043
    31 Regional Clinical Research Endwell New York United States 13760
    32 Long Island Clinical Research Associates Great Neck New York United States 11021
    33 Long Island Gastrointestinal Research Group Great Neck New York United States 11023
    34 Research Associates of New York New York New York United States 10075
    35 Vital Research Greensboro North Carolina United States 27408
    36 Gastroenterology Specialists, Inc Canton Ohio United States 44718
    37 Memorial Research Center Chattanooga Tennessee United States 37404
    38 Gastroenterology Associates Clinical Research Kingsport Tennessee United States 37660
    39 Nashville Medical Research Institute Nashville Tennessee United States 37205
    40 Harris Methodist Fort Worth Hospital Fort Worth Texas United States 76104
    41 Kelsey-Seybold Clinic Houston Texas United States 77005
    42 Clinical Trials of Texas, Inc. San Antonio Texas United States 78229
    43 Stone Oak Research Foundation San Antonio Texas United States 78258
    44 Blue Ridge Medical Research Lynchburg Virginia United States 24502
    45 Digestive and Liver Disease Specialists Norfolk Virginia United States 23502
    46 Aurora Advanced Healthcare, Inc. - Clinical Research Center Milwaukee Wisconsin United States 53209
    47 CIMEL Lanus Buenos Aires Argentina B1824KAS
    48 Instituto Gamma Rosario Santa Fe Argentina S2000DFD
    49 Hospital Bocalandro Buenos Aires Argentina B1657BHD
    50 Hospital Heroes de Malvinas Buenos Aires Argentina B1722FJN
    51 GEDYT Buenos Aires Argentina C1117AAA
    52 Sanatorio Guemes Buenos Aires Argentina C1180AAX
    53 Cibic S.A. Santa Fe Argentina S2000BCG
    54 The Canberra Hospital Garran Australian Capital Territory Australia 2605
    55 Ballarat Base Hospital Ballarat Victoria Australia 3350
    56 St Vincent's Hospital (Melb) LTD Melbourne Victoria Australia 3065
    57 Royal Adelaide Hospital Adelaide Australia 5000
    58 Royal Prince Albert Hospital Camperdown Australia 2050
    59 Frankston Private Frankston Australia 3199
    60 Bayside Gastroenterology Frankston Australia VIC 3199
    61 Fremantle Hospital Fremantle Australia 6160
    62 Ugasend S.A Barranquilla Colombia
    63 Clinica Colsinatas SA Bogota Colombia
    64 FOQUS, Centro de Investigacion Clinica Bogota Colombia
    65 Fundacion Clinica Abood Shaio Bogota Colombia
    66 Hospital Universitario San Ignacio Bogota Colombia
    67 Clinica Las Americas Medellin Colombia
    68 CHU de Strasbourg Strasbourg Alsace France 67200
    69 Hepato Gastro Enterology Nantes Brittany France 44033
    70 Hopital Charles Nicolle Rouen Normandy France 76031
    71 Hopital Beaujon Clichy Paris France 92118
    72 Cabinet de Gastro-enterologie du Dr Alain Thevenin Saint Quentin Picardie France 02100
    73 Hopital I'Archet Nice Provence-Alpes-Côte d'Azur France 06200
    74 Clinique Bouchard Marseille Provence-Alpes-Côte-d'Azur France 13000
    75 CHU de Grenoble Grenoble Rhone-Alpes France 38043
    76 Cabinet du Dr Olivier Delette Lille France 59000
    77 Dr Michel Regensberg Paris France 75017
    78 Baby Memorial Hospital Calicut Kerala India 673004
    79 Lakeshore Hospital & Research Centre Ltd Cochin Kerala India 682304
    80 Sree Gokulam Medical College and Research Foundation Trivandrum Kerala India 695607
    81 Dayanand Medical College and Hospital Ludhiana Punjab India 141001
    82 S R Kalla Memorial Hospital Jaipur Rajasthan India
    83 Aceer Chennai Tamil Nadu India 600020
    84 Institute of Postgraduate Medical Education and Research Kolkata West Bengal India 700020
    85 Brahmin Mitra Mandal Society Ahmedabad India 380006
    86 Ruby Hall Clinic Pune India 411 001
    87 Krishna Institute of Medical Sciences Secunderabad India 500 003
    88 Emek Medical Center Afula Israel 18101
    89 Barzilai Medical Centre Ashkelon Israel 78278
    90 Soroka Medical Center Beer Sheva Israel 84101
    91 Bnai Zion Medical Center Haifa Israel 31048
    92 Rambam Medical Center Haifa Israel 63106
    93 Hadassah Ein-Karem Medical Center Jerusalem Israel
    94 Meir Medical Centre Kfar-Saba Israel
    95 Rabin Medical Center Petah-Tikva Israel 49100
    96 Kaplan Medical Center Rechovot Israel
    97 The Tel Aviv Sourasky Medical Center Tel Aviv Israel 64239
    98 The Chaim Sheba Medical Center Tel Hashomer Israel 52621
    99 Assaf Harofeh Medical Center Zerifin Israel 70300
    100 Shakespeare Specialist Group Takapuna Auckland New Zealand
    101 Auckland City Hospital Auckland New Zealand
    102 CURT Medical Trials Trust Board Christchurch New Zealand
    103 Dunedin Hospital Dunedin New Zealand
    104 Waikato Hospital Hamilton New Zealand 3240
    105 Tauranga Hospital Tauranga New Zealand
    106 Hospital Valle de Hebron Barcelona Spain 08035
    107 Hospital Universitario de Bellvitge Barcelona Spain 08907
    108 Hospital Son Dureta Palma de Mallorca Spain 07014
    109 Hospital de Donostia San Sebastian Spain 20014
    110 Hospital General Universitario de Valencia Valencia Spain 46014
    111 University Hospital/Eastern Hospital Goteborg Sweden 41685
    112 University Hospital Linköping Linköping Sweden 58185
    113 VO Internmedicin Stockholm Sweden 11883
    114 Karolinska University Hospital Stockholm Sweden 17176
    115 Danderyd Hospital Stockholm Sweden 18288
    116 Kirurgkliniken Uppsala Sweden
    117 Norfolk/Norwich University Hospital Norwich East Anglia United Kingdom NR4 7UY
    118 St Mark's Hospital Harrow London United Kingdom HA1 3UJ
    119 King's College Hospital London United Kingdom SE5 9RS
    120 Chelsea & Westminster Hospital London United Kingdom SW10 9NH
    121 Imperial College London London United Kingdom W12 0NN

    Sponsors and Collaborators

    • Shire

    Investigators

    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Shire
    ClinicalTrials.gov Identifier:
    NCT00545740
    Other Study ID Numbers:
    • SPD476-313
    • 2007-004895-37
    First Posted:
    Oct 17, 2007
    Last Update Posted:
    Jun 14, 2021
    Last Verified:
    Jun 1, 2021
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo
    Arm/Group Description 1.2 g administered orally once daily 2.4 g administered orally once daily 4.8 g administered orally once daily Placebo administered orally once daily
    Period Title: Overall Study
    STARTED 145 145 151 149
    COMPLETED 70 62 55 78
    NOT COMPLETED 75 83 96 71

    Baseline Characteristics

    Arm/Group Title SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo Total
    Arm/Group Description 1.2 g administered orally once daily 2.4 g administered orally once daily 4.8 g administered orally once daily Placebo administered orally once daily Total of all reporting groups
    Overall Participants 145 145 151 149 590
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55.1
    (11.11)
    54.5
    (11.96)
    54.5
    (11.93)
    57.1
    (10.42)
    55.3
    (11.39)
    Age, Customized (Count of Participants)
    18 to <35 years
    3
    2.1%
    11
    7.6%
    8
    5.3%
    3
    2%
    25
    4.2%
    35 to <45 years
    20
    13.8%
    17
    11.7%
    26
    17.2%
    14
    9.4%
    77
    13.1%
    45 to <55 years
    49
    33.8%
    39
    26.9%
    36
    23.8%
    37
    24.8%
    161
    27.3%
    55 to <65 years
    43
    29.7%
    46
    31.7%
    51
    33.8%
    62
    41.6%
    202
    34.2%
    >= 65 years
    28
    19.3%
    30
    20.7%
    29
    19.2%
    31
    20.8%
    118
    20%
    Sex/Gender, Customized (Count of Participants)
    Female
    64
    44.1%
    69
    47.6%
    71
    47%
    71
    47.7%
    275
    46.6%
    Male
    79
    54.5%
    74
    51%
    79
    52.3%
    76
    51%
    308
    52.2%
    Region of Enrollment (Count of Participants)
    Argentina
    5
    3.4%
    3
    2.1%
    4
    2.6%
    3
    2%
    15
    2.5%
    Australia
    3
    2.1%
    5
    3.4%
    6
    4%
    5
    3.4%
    19
    3.2%
    Colombia
    19
    13.1%
    18
    12.4%
    18
    11.9%
    19
    12.8%
    74
    12.5%
    France
    5
    3.4%
    6
    4.1%
    6
    4%
    6
    4%
    23
    3.9%
    India
    4
    2.8%
    2
    1.4%
    3
    2%
    4
    2.7%
    13
    2.2%
    Israel
    24
    16.6%
    24
    16.6%
    23
    15.2%
    24
    16.1%
    95
    16.1%
    New Zealand
    3
    2.1%
    4
    2.8%
    4
    2.6%
    4
    2.7%
    15
    2.5%
    Spain
    1
    0.7%
    1
    0.7%
    4
    2.6%
    2
    1.3%
    8
    1.4%
    Sweden
    9
    6.2%
    9
    6.2%
    11
    7.3%
    9
    6%
    38
    6.4%
    United Kingdom
    3
    2.1%
    3
    2.1%
    3
    2%
    4
    2.7%
    13
    2.2%
    United States
    69
    47.6%
    70
    48.3%
    69
    45.7%
    69
    46.3%
    277
    46.9%

    Outcome Measures

    1. Secondary Outcome
    Title Percent of Subjects Who Were CT-Recurrence Free of Diverticulitis
    Description CT-recurrence of diverticulitis is defined as: a positive spiral CT scan for diverticulitis showing, at a minimum, fat stranding with or without bowel wall thickening >5 mm or surgical intervention for diverticular disease. Withdrawals considered as CT-recurrences.
    Time Frame Up to 104 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) consists of all subjects who were randomized and took at least 1 dose of investigational product.
    Arm/Group Title SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo
    Arm/Group Description 1.2 g administered orally once daily 2.4 g administered orally once daily 4.8 g administered orally once daily Placebo administered orally once daily
    Measure Participants 143 143 150 147
    Number [percentage of subjects]
    61.5
    62.2
    52.7
    63.9
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection SPD476 (4.8 g), Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.063
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection SPD476 (2.4 g), Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.736
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection SPD476 (1.2 g), Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.780
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    2. Secondary Outcome
    Title Number of CT Scans Performed Within 7 Days of Suspected Recurrence of Diverticulitis That Were Positive
    Description A positive CT scan was defined as a CT scan that showed bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader.
    Time Frame Up to 104 weeks

    Outcome Measure Data

    Analysis Population Description
    Suspected Recurrence of Diverticulitis consists of subjects in the Full Analysis Set who had a CT scan performed. Since subjects may have had more than one suspected recurrence, counts are of the number of CT scans, not the number of subjects.
    Arm/Group Title SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo
    Arm/Group Description 1.2 g administered orally once daily 2.4 g administered orally once daily 4.8 g administered orally once daily Placebo administered orally once daily
    Measure Participants 52 49 55 46
    Positive
    37
    39
    55
    38
    Presence of abdominal pain
    30
    39
    54
    37
    15% increase in WBC from baseline
    17
    24
    28
    24
    Presence in abdominal pain + 15% increase in WBC
    17
    24
    28
    23
    3. Primary Outcome
    Title Percent of Subjects Without Recurrence of Diverticulitis
    Description Recurrence of diverticulitis is defined as the presence of each and all of the following 3 items: 1) abdominal pain, 2) a 15% increase in white blood cell count from baseline, 3) bowel wall thickening (>5 mm) and/or fat stranding as evidenced by spiral computerized axial tomography (CT) scan; OR surgical intervention for diverticular disease. Withdrawals are considered as recurrences.
    Time Frame Up to 104 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) consists of all subjects who were randomized and took at least 1 dose of investigational product.
    Arm/Group Title SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo
    Arm/Group Description 1.2 g administered orally once daily 2.4 g administered orally once daily 4.8 g administered orally once daily Placebo administered orally once daily
    Measure Participants 143 143 150 147
    Number [percentage of subjects]
    62.2
    62.9
    52.7
    64.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection SPD476 (4.8 g), Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.047
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection SPD476 (2.4 g), Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.741
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection SPD476 (1.2 g), Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.780
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    4. Secondary Outcome
    Title Number of CT Scans Performed Within 7 Days of Suspected Recurrence of Diverticulitis That Were Negative
    Description A negative CT scan was defined as a CT scan that did not show bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader.
    Time Frame Up to 104 weeks

    Outcome Measure Data

    Analysis Population Description
    Suspected Recurrence of Diverticulitis consists of subjects in the Full Analysis Set who had a CT scan performed. Since subjects may have had more than one suspected recurrence, counts are of the number of CT scans, not the number of subjects.
    Arm/Group Title SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo
    Arm/Group Description 1.2 g administered orally once daily 2.4 g administered orally once daily 4.8 g administered orally once daily Placebo administered orally once daily
    Measure Participants 52 49 55 46
    Negative
    19
    10
    5
    10
    Presence of abdominal pain
    19
    8
    5
    7
    15% increase in WBC from baseline
    5
    2
    2
    1
    Presence in abdominal pain + 15% increase in WBC
    5
    2
    2
    1
    5. Secondary Outcome
    Title Number of CT Scans Performed More Than 7 Days From Suspected Recurrence of Diverticulitis That Were Positive
    Description A positive CT scan was defined as a CT scan that showed bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader.
    Time Frame Up to 104 weeks

    Outcome Measure Data

    Analysis Population Description
    Suspected Recurrence of Diverticulitis consists of subjects in the Full Analysis Set who had a CT scan performed. Since subjects may have had more than one suspected recurrence, counts are of the number of CT scans, not the number of subjects.
    Arm/Group Title SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo
    Arm/Group Description 1.2 g administered orally once daily 2.4 g administered orally once daily 4.8 g administered orally once daily Placebo administered orally once daily
    Measure Participants 52 49 55 46
    Positive
    0
    0
    1
    1
    Presence of abdominal pain
    0
    0
    1
    1
    15% increase in WBC from baseline
    0
    0
    0
    0
    Presence of abdominal pain + 15% increase in WBC
    0
    0
    0
    0
    6. Secondary Outcome
    Title Number of CT Scans Performed More Than 7 Days From Suspected Recurrence of Diverticulitis That Were Negative
    Description A negative CT scan was defined as a CT scan that did not show bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader.
    Time Frame Up to 104 weeks

    Outcome Measure Data

    Analysis Population Description
    Suspected Recurrence of Diverticulitis consists of subjects in the Full Analysis Set who had a CT scan performed. Since subjects may have had more than one suspected recurrence, counts are of the number of CT scans, not the number of subjects.
    Arm/Group Title SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo
    Arm/Group Description 1.2 g administered orally once daily 2.4 g administered orally once daily 4.8 g administered orally once daily Placebo administered orally once daily
    Measure Participants 52 49 55 46
    Negative
    0
    3
    2
    3
    Presence of abdominal pain
    0
    2
    2
    3
    15% increase in WBC from baseline
    0
    1
    0
    1
    Presence of abdominal pain + 15% increase in WBC
    0
    0
    0
    1
    7. Secondary Outcome
    Title Percent of Subjects Requiring Surgery for Diverticulitis
    Description
    Time Frame Up to 104 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set consists of all subjects who were randomized and took at least 1 dose of investigational product.
    Arm/Group Title SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo
    Arm/Group Description 1.2 g administered orally once daily 2.4 g administered orally once daily 4.8 g administered orally once daily Placebo administered orally once daily
    Measure Participants 143 143 150 147
    Number [percentage of subjects]
    2.8
    2.8
    3.3
    2.0

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo
    Arm/Group Description 1.2 g administered orally once daily 2.4 g administered orally once daily 4.8 g administered orally once daily Placebo administered orally once daily
    All Cause Mortality
    SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 16/143 (11.2%) 15/143 (10.5%) 18/150 (12%) 16/147 (10.9%)
    Blood and lymphatic system disorders
    Iron deficiency anemia 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Cardiac disorders
    Angina pectoris 2/143 (1.4%) 1/143 (0.7%) 1/150 (0.7%) 0/147 (0%)
    Coronary artery disease 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Myocardial ischemia 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Acute myocarcial infarction 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 2/147 (1.4%)
    Coronary artery insufficiency 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Ear and labyrinth disorders
    Vertigo positional 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Endocrine disorders
    Autoimmune thyroiditis 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Eye disorders
    Retinal detachment 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Gastrointestinal disorders
    Dyspepsia 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Gastritis 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Pancreatitis 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Pancreatitis acute 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Enterovesical fistula 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Gastrointestinal hemorrhage 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Abdominal pain 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 2/147 (1.4%)
    Large intestine perforation 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    Peritoneal hematoma 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    General disorders
    Pyrexia 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Chills 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Non-cardiac chest pain 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    Infections and infestations
    Urinary tract infection 0/143 (0%) 0/143 (0%) 2/150 (1.3%) 0/147 (0%)
    Gastroenteritis 0/143 (0%) 1/143 (0.7%) 1/150 (0.7%) 0/147 (0%)
    Sepsis 1/143 (0.7%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Clostridial infection 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Kidney infection 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Pneumonia primary atypical 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Viral infection 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Cellulitis 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Pneumonia 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Endophthalmitis 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Gastrointestinal infection 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Injury, poisoning and procedural complications
    Road traffic accident 2/143 (1.4%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    Near drowning 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Concussion 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    Femoral neck fracture 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    Skin injury 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    Humerus fracture 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Joint dislocation 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Metabolism and nutrition disorders
    Hypercalcemia 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine cancer 2/143 (1.4%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    Prostate cancer 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Breast cancer 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Thyroid neoplasm 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    Breast cancer in situ 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Laryngeal cancer 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Thyroid cancer 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Nervous system disorders
    Ischemic stroke 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Movement disorder 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Syncope 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Cerebral ischemia 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Psychiatric disorders
    Alcoholism 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Bipolar II disorder 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Confusional state 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Bipolar disorder 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Renal and urinary disorders
    Nephrolithiasis 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Pelvi-ureteric obstruction 0/143 (0%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Bladder prolapse 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Renal colic 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    Renal failure acute 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    Stress urinary incontinence 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Ovarian cyst 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 1/143 (0.7%) 0/143 (0%) 1/150 (0.7%) 0/147 (0%)
    Nasal septum deviation 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Sinus polyp 0/143 (0%) 1/143 (0.7%) 0/150 (0%) 0/147 (0%)
    Pulmonary hypertension 1/143 (0.7%) 0/143 (0%) 0/150 (0%) 0/147 (0%)
    Asthma 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Vascular disorders
    Aortic Aneurysm 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Hypertension 0/143 (0%) 0/143 (0%) 0/150 (0%) 1/147 (0.7%)
    Other (Not Including Serious) Adverse Events
    SPD476 (1.2 g) SPD476 (2.4 g) SPD476 (4.8 g) Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 109/143 (76.2%) 106/143 (74.1%) 101/150 (67.3%) 112/147 (76.2%)
    Gastrointestinal disorders
    Abdominal pain 17/143 (11.9%) 16/143 (11.2%) 18/150 (12%) 16/147 (10.9%)
    Diarrhea 13/143 (9.1%) 12/143 (8.4%) 12/150 (8%) 12/147 (8.2%)
    Flatulence 9/143 (6.3%) 5/143 (3.5%) 3/150 (2%) 4/147 (2.7%)
    Constpation 7/143 (4.9%) 3/143 (2.1%) 5/150 (3.3%) 8/147 (5.4%)
    General disorders
    Nausea 10/143 (7%) 1/143 (0.7%) 6/150 (4%) 5/147 (3.4%)
    Infections and infestations
    Urinary tract infection 14/143 (9.8%) 12/143 (8.4%) 8/150 (5.3%) 17/147 (11.6%)
    Nasopharyngitis 6/143 (4.2%) 15/143 (10.5%) 7/150 (4.7%) 13/147 (8.8%)
    Upper respiratory tract infection 9/143 (6.3%) 3/143 (2.1%) 10/150 (6.7%) 14/147 (9.5%)
    Sinusitis 9/143 (6.3%) 7/143 (4.9%) 5/150 (3.3%) 8/147 (5.4%)
    Influenza 5/143 (3.5%) 11/143 (7.7%) 4/150 (2.7%) 3/147 (2%)
    Bronchitis 7/143 (4.9%) 8/143 (5.6%) 3/150 (2%) 3/147 (2%)
    Musculoskeletal and connective tissue disorders
    Back pain 8/143 (5.6%) 5/143 (3.5%) 8/150 (5.3%) 12/147 (8.2%)
    Arthralgia 7/143 (4.9%) 5/143 (3.5%) 4/150 (2.7%) 13/147 (8.8%)
    Nervous system disorders
    Headache 13/143 (9.1%) 6/143 (4.2%) 14/150 (9.3%) 10/147 (6.8%)
    Vascular disorders
    Hypertension 5/143 (3.5%) 8/143 (5.6%) 6/150 (4%) 1/147 (0.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.

    Results Point of Contact

    Name/Title Study Director
    Organization Shire
    Phone +1 866 842 5335
    Email ClinicalTransparency@shire.com
    Responsible Party:
    Shire
    ClinicalTrials.gov Identifier:
    NCT00545740
    Other Study ID Numbers:
    • SPD476-313
    • 2007-004895-37
    First Posted:
    Oct 17, 2007
    Last Update Posted:
    Jun 14, 2021
    Last Verified:
    Jun 1, 2021