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TerminatedNCT01016262Updated Aug 28, 2019Results posted

Efficacy and Safety Study of MAX-002 Suppository Versus Placebo and Active Medicine in Mild to Moderate Ulcerative Proctitis

A Phase 3 interventional study of MAX-002 and Placebo in Proctitis, Ulcerative, sponsored by Forest Laboratories. Terminated at 40 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-08-28.

Sponsored by Forest Laboratories · Phase 3, Interventional, and Treatment

Why this study was terminated
The decision was taken solely for business/administrative reasons, no safety considerations entered into this. Ongoing randomized patients to complete.
Phase
Phase 3
Study type
Interventional
Enrollment
119
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This is a prospective, multicenter, double-blind (DB), controlled, randomized, parallel group comparison Phase 3a study to evaluate the efficacy and safety of new mesalamine suppositories (MAX-002) as compared to placebo and active medicine after 6 weeks of treatment in adults with mild to moderate ulcerative proctitis (UP).

Read the detailed description

The present study consists of screening period (2 weeks before randomization), DB phase (6 weeks), OL phase (8 weeks) and follow-up visits at Week 3, Week 6 and Week 14. Participants who are eligible will be randomized to receive 1g MAX-002, 1g Canasa® and placebo suppository once daily in the DB phase. Participants who complete or discontinue the study at Week 6 will either receive 1g MAX-002 suppositories on a voluntary basis, standard care treatment as per investigator's discretion or no treatment during the next 8 weeks of the OL phase. Total duration of treatment will be of 14 weeks. Efficacy will primarily be evaluated by percentage of participants who show response as per Mayo DAI Score at Week 6. Participants' safety will be monitored throughout the study.

02

Conditions studied

  • Proctitis, Ulcerative

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Keywords

  • Ulcerative proctitis
  • Proctocolitis
  • Inflammatory Bowel Disease
  • Gastrointestinal Diseases
  • Colonic Diseases
  • Mesalamine
  • 5-ASA
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Participants who are 18 years old or older
  • Participants with total Mayo DAI score between 5 to 10 at Screening and participants with score of 2 or more for the rectal bleeding and for the findings of flexible proctosigmoidoscopy or colonoscopy sub-scores of the Mayo DAI
  • Participants with confirmed mild to moderate active UP not extending above rectum as evidenced by flexible proctosigmoidoscopy and histopathology assessments
  • Female participants of child-bearing age who have negative serum beta-human chorionic gonadotropin (β-HCG) at the time of entry into the study
  • Female participants of child-bearing age who use medically acceptable form of birth control
  • Participants who are smokers and non-smokers must not change their smoking habits or nicotine use during the DB treatment period
  • Participants who are literate and have legal ability to sign informed consent form

Exclusion criteria

Exclusion Criteria:

  • Participants with other digestive diseases interfering with the measurement of any sub-score of the Mayo DAI
  • Participants with known presence or suspicion of malignant disease of the digestive system or presence or history of neoplasms other than carcinoma in situ of the cervix or basal carcinoma of the skin
  • Participants with clinically significant electrocardiographic abnormalities that would compromise its participation in the study
  • Participants who are chronically using oral 5-aminosalicylic acid (5-ASA) at a dose greater than 4g daily, change in the oral 5-ASA dosing, or use of any form of rectal 5-ASA formulations during the 30 days prior to randomization
  • Participants with significant use of corticosteroids ,immunosuppressant's or biologic response modifiers that may have a therapeutic effect on ulcerative proctitis during the 45 days before the date of consent
  • Participants who use any rectally administered medicine during the 30 days prior to randomization
  • Participants who have contraindication to the use of mesalamine or suppository vehicle, analgesia, flexible proctosigmoidoscopy or colonoscopy
  • Participants who have blood parameters of grade 3 or higher on the common terminology criteria for adverse events (CTCAE) 5-point scale
  • Participants with severe renal or hepatic impairment with parameters of grade 3 or higher on the CTCAE
  • Participants with clinically significant urinary tract obstruction and history of idiopathic pancreatitis
  • Participants with presence of other known clinically significant medical and/or psychological illnesses precluding participation
  • Participants who participate in clinical studies other than observational studies during the 90 days before the date of the informed consent form signature
  • Participants who are unable or unwilling to complete the follow-up evaluations required for the study
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
119 participants (actual)

Study arms

  • Experimental
    MAX-002

    Drug: MAX-002

  • Placebo comparator
    Placebo

    Drug: Placebo

  • Active comparator
    Canasa®

    Drug: Canasa®

Interventions

  • DrugMAX-002

    MAX-002 suppository 1 gram (g) rectally once daily at bedtime for 6 weeks during the DB phase. Participants will then receive either MAX-002 suppository, standard care treatment or no treatment (as per Investigator's judgment) for 8 weeks during the open-label (OL) phase.

    Also known as: Mesalamine

  • DrugPlacebo

    Matching placebo suppository rectally once daily at bedtime for 6 weeks during the DB phase. Participants will then receive either MAX-002 suppository, standard care treatment or no treatment (as per Investigator's judgment) for 8 weeks during the OL phase.

  • DrugCanasa®

    Canasa® suppository 1 g rectally once daily at bedtime for 6 weeks during the DB phase. Participants will then receive either MAX-002 suppository, standard care treatment or no treatment (as per Investigator's judgment) for 8 weeks during the OL phase.

    Also known as: Mesalamine

05

What researchers measure

Primary outcomes

  1. Percentage of Participants Who Were Responders at Week 6

    Participants were considered as responders if they had total Mayo Disease Activity Index (DAI) score less than 3 points and no individual sub-scores greater than or equal to 2. Mayo DAI is a semi-quantitative scale which consists of 4 sub-scales: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy or colonoscopy and physician global assessment, each sub-scale ranged from 0 to 3 (0=normal, 3=severe). The total Mayo DAI score ranges from 0 (normal or inactive disease) to 12 (severe disease).

    Time frame: Week 6

Secondary outcomes

  1. Percentage of Participants Who Were Responders at Week 3

    Participants considered as responders if they had total Mayo DAI score less than 3 points and no individual sub-scores greater than or equal to 2. Mayo DAI is a semi-quantitative scale which consists of 4 sub-scales: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy or colonoscopy and physician global assessment, each sub-scale ranged from 0 to 3 (0=normal, 3=severe). The total Mayo DAI score ranges from 0 (normal or inactive disease) to 12 (severe disease).

    Time frame: Week 3

  2. Time to Relief of Rectal Bleeding

    Time to relief of rectal bleeding was defined as number of days from randomization (Day 1) up to the first date of 3 consecutive days without observation of rectal bleeding during the double-blind phase.

    Time frame: Day 1 up to Week 6

  3. Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6

    The IBDQ is used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 domains of wellness: bowel symptoms (10 questions), systemic symptoms (5 questions), social symptoms (5 questions) and emotional function (12 questions). The response to each question is graded on 7-point likert scale, ranging from 1 (worst aspect) to 7 (best aspect). The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score ranges from 32 to 224 with higher scores indicating a better quality of life.

    Time frame: Baseline, Week 6

  4. Time to Relief of Tenesmus

    Time to relief of tenesmus (feeling of constantly needing to pass stools, even if the bowels are already empty) was defined as the number of days from randomization (Day 1) up to the first date of 3 consecutive days without observation of tenesmus during the double-blind phase.

    Time frame: Day 1 up to Week 6

06

Results

Posted Aug 28, 2019
Limitations and caveats
The study was terminated because of business/administrative reasons and not because of safety considerations.

Participant flow

Double-blind Phase
Participant flow — Double-blind Phase
MilestoneMAX-002 (Double-blind Phase)Canasa® (Double-blind Phase)Placebo (Double-blind Phase)MAX-002 (Open-label Phase)Standard Care Treatment (Open-label Phase)No Treatment (Open-label Phase)
Started413939000
Completed403830000
Not completed119000
Withdrew: Adverse event001000
Withdrew: Lack of efficacy105000
Withdrew: Disease progression012000
Withdrew: Withdrawal of informed consent001000
Open-Label Phase
Participant flow — Open-Label Phase
MilestoneMAX-002 (Double-blind Phase)Canasa® (Double-blind Phase)Placebo (Double-blind Phase)MAX-002 (Open-label Phase)Standard Care Treatment (Open-label Phase)No Treatment (Open-label Phase)
Started000445220
Completed000425020
Not completed000220
Withdrew: Adverse event000100
Withdrew: Lost to follow-up000010
Withdrew: Lack of efficacy000100
Withdrew: Withdrawal of informed consent000010

Outcome measures

PrimaryPercentage of Participants Who Were Responders at Week 6

Participants were considered as responders if they had total Mayo Disease Activity Index (DAI) score less than 3 points and no individual sub-scores greater than or equal to 2. Mayo DAI is a semi-quantitative scale which consists of 4 sub-scales: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy or colonoscopy and physician global assessment, each sub-scale ranged from 0 to 3 (0=normal, 3=severe). The total Mayo DAI score ranges from 0 (normal or inactive disease) to 12 (severe disease).

Time frame:
Week 6
Reported as:
Number · percentage of participants
Percentage of Participants Who Were Responders at Week 6
percentage of participantsMAX-002 (Double-blind Phase)Canasa® (Double-blind Phase)Placebo (Double-blind Phase)
Percentage of Participants Who Were Responders at Week 656.146.223.1
Statistical analysis
  • MAX-002 (Double-blind Phase) vs Placebo (Double-blind Phase) · Cochran-Mantel-Haenszel · p = 0.0047 (Statistical significance was assessed at the two-sided 5% level. As there was only a single pre-specified primary analysis, there was no adjustment for multiplicity.)
  • Canasa® (Double-blind Phase) vs Placebo (Double-blind Phase) · Cochran-Mantel-Haenszel · p = 0.0346 (Statistical significance was assessed at the two-sided 5% level. As there was only a single pre-specified primary analysis, there was no adjustment for multiplicity.)
SecondaryPercentage of Participants Who Were Responders at Week 3

Participants considered as responders if they had total Mayo DAI score less than 3 points and no individual sub-scores greater than or equal to 2. Mayo DAI is a semi-quantitative scale which consists of 4 sub-scales: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy or colonoscopy and physician global assessment, each sub-scale ranged from 0 to 3 (0=normal, 3=severe). The total Mayo DAI score ranges from 0 (normal or inactive disease) to 12 (severe disease).

Time frame:
Week 3
Reported as:
Number · percentage of participants
Percentage of Participants Who Were Responders at Week 3
percentage of participantsMAX-002 (Double-blind Phase)Canasa® (Double-blind Phase)Placebo (Double-blind Phase)
Percentage of Participants Who Were Responders at Week 336.638.512.8
SecondaryTime to Relief of Rectal Bleeding

Time to relief of rectal bleeding was defined as number of days from randomization (Day 1) up to the first date of 3 consecutive days without observation of rectal bleeding during the double-blind phase.

Time frame:
Day 1 up to Week 6
Reported as:
Median · days
Time to Relief of Rectal Bleeding
daysMAX-002 (Double-blind Phase)Canasa® (Double-blind Phase)Placebo (Double-blind Phase)
Time to Relief of Rectal Bleeding6 (4 to 9)5 (3 to 12)21 (7 to NA)
SecondaryChange From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6

The IBDQ is used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 domains of wellness: bowel symptoms (10 questions), systemic symptoms (5 questions), social symptoms (5 questions) and emotional function (12 questions). The response to each question is graded on 7-point likert scale, ranging from 1 (worst aspect) to 7 (best aspect). The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score ranges from 32 to 224 with higher scores indicating a better quality of life.

Time frame:
Baseline, Week 6
Reported as:
Mean · units on a scale
Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6
units on a scaleMAX-002 (Double-blind Phase)Canasa® (Double-blind Phase)Placebo (Double-blind Phase)
Baseline (n= 41, 39, 39)153.45 ± 35.03153.19 ± 38.75149.18 ± 32.40
Change at Week 6 (n= 41, 39, 31)30.59 ± 28.9542.42 ± 31.2624.48 ± 27.29
SecondaryTime to Relief of Tenesmus

Time to relief of tenesmus (feeling of constantly needing to pass stools, even if the bowels are already empty) was defined as the number of days from randomization (Day 1) up to the first date of 3 consecutive days without observation of tenesmus during the double-blind phase.

Time frame:
Day 1 up to Week 6
Reported as:
Median · days
Time to Relief of Tenesmus
daysMAX-002 (Double-blind Phase)Canasa® (Double-blind Phase)Placebo (Double-blind Phase)
Time to Relief of Tenesmus3 (1 to 4)2 (1 to 5)1 (1 to 10)

Adverse events

Collected over Baseline up to end of study (Week 14). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
MAX-002 (Double-blind Phase)0/40 (0%)0/40 (0%)14/40 (35%)
Canasa® (Double-blind Phase)0/41 (0%)1/41 (2.4%)16/41 (39%)
Placebo (Double-blind Phase)0/38 (0%)0/38 (0%)20/38 (52.6%)
MAX-002 (Open-label Phase)0/44 (0%)1/44 (2.3%)20/44 (45.5%)
Standard Care Treatment (Open-label Phase)0/52 (0%)0/52 (0%)20/52 (38.5%)
No Treatment (Open-label Phase)0/20 (0%)0/20 (0%)9/20 (45%)
Most frequent serious events
Most frequent serious events
EventMAX-002 (Double-blind Phase)Canasa® (Double-blind Phase)Placebo (Double-blind Phase)MAX-002 (Open-label Phase)Standard Care Treatment (Open-label Phase)No Treatment (Open-label Phase)
Back PainMusculoskeletal and connective tissue disorders0/401/410/380/440/520/20
Non-cardiac chest painGeneral disorders0/400/410/381/440/520/20
Most frequent other events
Showing 10 of 110
Most frequent other events
EventMAX-002 (Double-blind Phase)Canasa® (Double-blind Phase)Placebo (Double-blind Phase)MAX-002 (Open-label Phase)Standard Care Treatment (Open-label Phase)No Treatment (Open-label Phase)
HeadacheNervous system disorders3/406/416/383/442/523/20
Abdominal painGastrointestinal disorders2/400/414/383/442/520/20
NauseaGastrointestinal disorders1/401/414/380/440/520/20
NasopharyngitisInfections and infestations1/402/413/383/443/522/20
Anorectal discomfortGastrointestinal disorders1/400/412/381/440/520/20
ToothacheGastrointestinal disorders2/400/410/380/441/520/20
Rectal haemorrhageGastrointestinal disorders0/400/411/380/440/521/20
Influenza like illnessGeneral disorders0/400/410/381/440/521/20
PharyngitisInfections and infestations1/400/410/380/442/521/20
TendonitisMusculoskeletal and connective tissue disorders0/400/410/380/440/521/20

Baseline characteristics

Intent-to-treat (ITT) population included all randomized participants.

Age, Continuous
Age, Continuous(years)MAX-002 (Double-blind Phase)Canasa® (Double-blind Phase)Placebo (Double-blind Phase)Total
Mean44.3 ± 13.5544.8 ± 11.7041.8 ± 12.8443.7 ± 12.69
Sex: Female, Male
Sex: Female, Male(Participants)MAX-002 (Double-blind Phase)Canasa® (Double-blind Phase)Placebo (Double-blind Phase)Total
Female19192361
Male22201658
07

Study locations

40 sites
  • Birmingham Gastroenterology Associates P.C.
    Birmingham, Alabama 35209, United States
  • Digestive Health Specialists of the Southeast
    Dothan, Alabama 36305, United States
  • Desert Sun Gastroenterology
    Tucson, Arizona 85710, United States
  • Rocky Mountain Gastroenterology Associates
    Thornton, Colorado 80229, United States
  • Litchfield County Gastroenterology and Associates
    Torrington, Connecticut 06790, United States
  • Clinical Research of South Florida
    Boynton Beach, Florida 33426, United States
  • Center for Gastrointestinal Disorders
    Hollywood, Florida 33021, United States
  • Gastroenterology Group of Naples
    Naples, Florida 34102, United States
  • Shafran Gastroenterology Center
    Winter Park, Florida 32789, United States
  • Digestive Research Associates
    Newnan, Georgia 30263, United States
  • Advanced Pain Care Clinic
    Evansville, Indiana 47714, United States
  • Gastrointestinal Associates
    Jackson, Mississippi 39202, United States
  • Center for Digestive & Liver Diseases Inc.
    Mexico, Missouri 65265, United States
  • South Jersey Gastroenterology
    Marlton, New Jersey 08053, United States
  • Synergy First Medical
    Brooklyn, New York 11230, United States
  • Research Associates of New York (RANY)
    New York, New York 10075, United States
  • Consultants for Clinical Research
    Cincinnati, Ohio 45219, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • Memphis Gastroenterology Group
    Germantown, Tennessee 38138, United States
  • The First Clinic
    Nashville, Tennessee 37203, United States
  • South Texas Research Alliance
    Laredo, Texas 78041, United States
  • Wisconsin Center for Advanced Research
    Milwaukee, Wisconsin 53215, United States
  • Gastroenterology & Hepatology Clinic
    Abbotsford, British Columbia V2S 3N5, Canada
  • Diamond Health Care Centre
    Vancouver, British Columbia V5Z 1N9, Canada
  • Surrey GI Clinic Research
    Guelph, Ontario N1H 3R3, Canada
  • St-Joseph's Healthcare Hamilton
    Hamilton, Ontario L8N 4A6, Canada
  • DHC Research
    Richmond Hill, Ontario L4B 3P8, Canada
  • Toronto Digestive Disease Associates Inc. (TDDA)
    Vaughan, Ontario L4L 4Y7, Canada
  • Hôpital Maisonneuve-Rosemont
    Montreal, Quebec H1T 2M4, Canada
  • Alpha Recherche Clinique
    Quebec, G2B 5S1, Canada
  • GASTROMED s.c.
    Bialystok, 15-351, Poland
  • Wojewódzki Szpital Specjalistyczny Oddz. Gastroenterologii
    Czestochowa, 42-200, Poland
  • SPZOZ Uniwersytecki Szpital Kliniczny
    Lodz, 90-153, Poland
  • SPZOZ Uniwersytecki Szpital Kliniczny
    Lodz, 90-549, Poland
  • Wojewodzki Szpital Specjalistyczny
    Lublin, 20-718, Poland
  • SP Szpital Kliniczny
    Lublin, 20-954, Poland
  • Szpital Kolejowy
    Pruszków, 05-800, Poland
  • MEDICOR - Centrum Medyczne
    Rzeszow, 35-068, Poland
  • Endoskopia SP. Z o.o.
    Sopot, 81-756, Poland
  • Gabinet Lekarski LECHMED
    Warszawa, 02-511, Poland
08

Registry details

Key details

Study ID
NCT01016262
Lead sponsor
Forest Laboratories
Responsible party
Sponsor
First posted
Nov 19, 2009
Start date
Nov 30, 2009
Primary completion
Jul 31, 2011
Completion
Sep 30, 2011
Results posted
Aug 28, 2019
Last update
Aug 28, 2019

Study contacts

Aptalis Medical Information
study director · Forest Laboratories

Oversight

Data monitoring committee
No
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