MACS1574: Myelodysplastic Syndrome (MDS) Gastrointestinal (GI) Tolerability Study
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
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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]
- 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
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.- CICL670A2417
- 2011-001077-13
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
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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
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 |
- CICL670A2417
- 2011-001077-13