MACS1574: Myelodysplastic Syndrome (MDS) Gastrointestinal (GI) Tolerability Study

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT01326845
Collaborator
(none)
12
10
2
9
1.2
0.1

Study Details

Study Description

Brief Summary

The objective of the study is to evaluate and compare the frequency and severity of GI adverse events in different dose administration regimens. The patient population consists of low or intermediate (int-1) risk myelodysplastic syndrome (MDS) patients with transfusional iron overload. The study patients are randomized to either a morning dose of 20 mg/kg/day deferasirox or an evening dose of the same. Patients are then followed up for 6 months for any GI events and are assessed using patient reported outcomes tools e.g. a patient diary.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Comparative Study of Different Deferasirox Administration Regimens on Gastrointestinal (GI) Tolerability in Low or Intermediate (Int-1) Risk MDS Myelodysplastic Syndrome Patients With Transfusional Iron Overload.
Study Start Date :
Dec 1, 2011
Actual Primary Completion Date :
Sep 1, 2012
Actual Study Completion Date :
Sep 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Deferasirox am

Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food

Drug: Deferasirox
Other Names:
  • ICL670
  • Experimental: Deferasirox pm

    Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal

    Drug: Deferasirox
    Other Names:
  • ICL670
  • Outcome Measures

    Primary Outcome Measures

    1. Difference in the Frequency of Overall Newly Occurring GI Adverse Events (AEs) in the Two Treatment Arms [3 months]

      Study was prematurely terminated and not powered for efficacy. Frequency of GI AEs during the overall study period is available in the AE tables reported in the safety section.

    Secondary Outcome Measures

    1. Difference in Frequency of Overall Newly Occurring GI AEs Between the Two Treatment Groups at Month 6. [6 months]

      Study was prematurely terminated and not powered for efficacy.

    2. Difference in Frequency of Specific Commonly Reported GI AEs Between the Two Treatment Groups [months 3 and 6.]

      Study was prematurely terminated and not powered for efficacy.

    3. Difference in Severity of Overall GI AEs Between the Two Treatment Groups [months 3 and 6.]

      Study was prematurely terminated and not powered for efficacy.

    4. Difference in Severity of Specific Commonly Reported GI Symptoms Between the Two Treatment Groups [months 3 and 6]

      Study was prematurely terminated and not powered for efficacy.

    5. Difference in Frequency and Severity of All Non-GI AEs Between the Two Treatment Groups [months 3 and 6]

      Study was prematurely terminated and not powered for efficacy.

    6. the Difference Between the Time From Baseline to the First Occurrence of GI AEs Between the Two Treatment Groups [3 months, 6 months]

      Study was prematurely terminated and not powered for efficacy.

    7. Difference in Severity of GI Symptoms, Bowel Habits and Level of Satisfaction From the Patient's Perspective Between the Two Treatment Groups [3 months, 6 months]

    8. Difference in Reducing Serum Ferritin After Each Month of Study Drug Administration Between the Two Groups [3 months, 6 months]

      Study was prematurely terminated and not powered for efficacy.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Written informed consent prior to any screening procedures

    • Male or female patients ≥ 18 years of age

    • Patient must weigh between 45-135 kg

    • Patients with low or intermediate (int-1) risk MDS, as determined by IPSS score or RA, RARS by WHO criteria. IPSS must be confirmed by a bone marrow examination within 6 months prior to study entry and must be hematologically stable

    Deferasirox naïve:

    Sexually active pre-menopausal female patients must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation

    Exclusion Criteria:
    • History or current GI disease

    • Systemic diseases which could prevent study treatments

    • Left ventricular ejection fraction< 50 % by echo cardiography

    • Serum creatinine > 1.2 x ULN at screening

    • Platelet counts < 25x 109/L except in cases where guidance is already given in the local deferasirox label

    • AST or ALT > 2.5 xULN at screening

    Other protocol-defined inclusion/exclusion criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Caen Cedex France 14033
    2 Novartis Investigative Site Brest France 29200
    3 Novartis Investigative Site Limoges cedex France 87042
    4 Novartis Investigative Site Pessac Cedex France 33604
    5 Novartis Investigative Site Vandoeuvre les Nancy France 54511
    6 Novartis Investigative Site Alessandria AL Italy 15100
    7 Novartis Investigative Site Torino TO Italy 10126
    8 Novartis Investigative Site Roma Italy 00133
    9 Novartis Investigative Site Bloemfontein South Africa 901
    10 Novartis Investigative Site Madrid Spain 28033

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01326845
    Other Study ID Numbers:
    • CICL670A2417
    • 2011-001077-13
    First Posted:
    Mar 31, 2011
    Last Update Posted:
    Mar 3, 2017
    Last Verified:
    Mar 1, 2017

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Deferasirox am Deferasirox pm
    Arm/Group Description Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal
    Period Title: Overall Study
    STARTED 7 5
    COMPLETED 0 0
    NOT COMPLETED 7 5

    Baseline Characteristics

    Arm/Group Title Deferasirox am Deferasirox pm Total
    Arm/Group Description Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal Total of all reporting groups
    Overall Participants 7 5 12
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    69.7
    (7.5)
    71.6
    (8.65)
    70.5
    (7.67)
    Sex: Female, Male (Count of Participants)
    Female
    3
    42.9%
    3
    60%
    6
    50%
    Male
    4
    57.1%
    2
    40%
    6
    50%

    Outcome Measures

    1. Primary Outcome
    Title Difference in the Frequency of Overall Newly Occurring GI Adverse Events (AEs) in the Two Treatment Arms
    Description Study was prematurely terminated and not powered for efficacy. Frequency of GI AEs during the overall study period is available in the AE tables reported in the safety section.
    Time Frame 3 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deferasirox am Deferasirox pm
    Arm/Group Description Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal
    Measure Participants 0 0
    2. Secondary Outcome
    Title Difference in Frequency of Overall Newly Occurring GI AEs Between the Two Treatment Groups at Month 6.
    Description Study was prematurely terminated and not powered for efficacy.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deferasirox am Deferasirox pm
    Arm/Group Description Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal
    Measure Participants 0 0
    3. Secondary Outcome
    Title Difference in Frequency of Specific Commonly Reported GI AEs Between the Two Treatment Groups
    Description Study was prematurely terminated and not powered for efficacy.
    Time Frame months 3 and 6.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deferasirox am Deferasirox pm
    Arm/Group Description Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal
    Measure Participants 0 0
    4. Secondary Outcome
    Title Difference in Severity of Overall GI AEs Between the Two Treatment Groups
    Description Study was prematurely terminated and not powered for efficacy.
    Time Frame months 3 and 6.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deferasirox am Deferasirox pm
    Arm/Group Description Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal
    Measure Participants 0 0
    5. Secondary Outcome
    Title Difference in Severity of Specific Commonly Reported GI Symptoms Between the Two Treatment Groups
    Description Study was prematurely terminated and not powered for efficacy.
    Time Frame months 3 and 6

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deferasirox am Deferasirox pm
    Arm/Group Description Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal
    Measure Participants 0 0
    6. Secondary Outcome
    Title Difference in Frequency and Severity of All Non-GI AEs Between the Two Treatment Groups
    Description Study was prematurely terminated and not powered for efficacy.
    Time Frame months 3 and 6

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deferasirox am Deferasirox pm
    Arm/Group Description Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal
    Measure Participants 0 0
    7. Secondary Outcome
    Title the Difference Between the Time From Baseline to the First Occurrence of GI AEs Between the Two Treatment Groups
    Description Study was prematurely terminated and not powered for efficacy.
    Time Frame 3 months, 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deferasirox am Deferasirox pm
    Arm/Group Description Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal
    Measure Participants 0 0
    8. Secondary Outcome
    Title Difference in Severity of GI Symptoms, Bowel Habits and Level of Satisfaction From the Patient's Perspective Between the Two Treatment Groups
    Description
    Time Frame 3 months, 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deferasirox am Deferasirox pm
    Arm/Group Description Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal
    Measure Participants 0 0
    9. Secondary Outcome
    Title Difference in Reducing Serum Ferritin After Each Month of Study Drug Administration Between the Two Groups
    Description Study was prematurely terminated and not powered for efficacy.
    Time Frame 3 months, 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deferasirox am Deferasirox pm
    Arm/Group Description Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal
    Measure Participants 0 0

    Adverse Events

    Time Frame 6 months
    Adverse Event Reporting Description
    Arm/Group Title ICL am ICL pm
    Arm/Group Description ICL am ICL pm
    All Cause Mortality
    ICL am ICL pm
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    ICL am ICL pm
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/7 (14.3%) 2/5 (40%)
    Blood and lymphatic system disorders
    Anaemia 0/7 (0%) 1/5 (20%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Leukaemia 1/7 (14.3%) 0/5 (0%)
    Vascular disorders
    Jugular vein thrombosis 0/7 (0%) 1/5 (20%)
    Other (Not Including Serious) Adverse Events
    ICL am ICL pm
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/7 (71.4%) 2/5 (40%)
    Blood and lymphatic system disorders
    Anaemia 2/7 (28.6%) 0/5 (0%)
    Neutropenia 0/7 (0%) 1/5 (20%)
    Gastrointestinal disorders
    Abdominal pain upper 0/7 (0%) 1/5 (20%)
    Diarrhoea 1/7 (14.3%) 0/5 (0%)
    Gastrointestinal disorder 1/7 (14.3%) 0/5 (0%)
    Nausea 2/7 (28.6%) 0/5 (0%)
    Vomiting 1/7 (14.3%) 0/5 (0%)
    General disorders
    Asthenia 2/7 (28.6%) 1/5 (20%)
    Oedema peripheral 2/7 (28.6%) 0/5 (0%)
    Infections and infestations
    Lyme disease 1/7 (14.3%) 0/5 (0%)
    Staphylococcal infection 0/7 (0%) 1/5 (20%)
    Upper respiratory tract infection 1/7 (14.3%) 0/5 (0%)
    Investigations
    Alanine aminotransferase increased 1/7 (14.3%) 0/5 (0%)
    Aspartate aminotransferase increased 1/7 (14.3%) 0/5 (0%)
    Blood alkaline phosphatase increased 1/7 (14.3%) 0/5 (0%)
    Blood creatinine increased 1/7 (14.3%) 0/5 (0%)
    Gamma-glutamyltransferase increased 1/7 (14.3%) 0/5 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 1/7 (14.3%) 0/5 (0%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 0/7 (0%) 1/5 (20%)
    Renal and urinary disorders
    Renal impairment 1/7 (14.3%) 0/5 (0%)
    Skin and subcutaneous tissue disorders
    Rash 1/7 (14.3%) 0/5 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01326845
    Other Study ID Numbers:
    • CICL670A2417
    • 2011-001077-13
    First Posted:
    Mar 31, 2011
    Last Update Posted:
    Mar 3, 2017
    Last Verified:
    Mar 1, 2017