Enteric-coated Mycophenolate Sodium (EC-MPS) and Mycophen... | NCT00400400

NCT00400400

Status Module

Sponsor/Collaborators Module

Oversight Module

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No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Enteric-coated mycophenolate sodium	Experimental	Enteric-coated mycophenolate sodium tablets taken orally twice a day (in the morning and in the evening) at a dose equimolar to the dose of mycophenolate mofetil the participant was taking prior to start of the study + Placebo to mycophenolate mofetil capsules taken orally twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.	Drug: Enteric-coated mycophenolate sodium (EC-MPS) Drug: Placebo to mycophenolate mofetil
Mycophenolate mofetil	Active Comparator	Mycophenolate mofetil capsules taken orally twice a day (in the morning and in the evening) at the dose the participant was taking prior to study start + Placebo to mycophenolate sodium tablets taken twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.	Drug: Mycophenolate mofetil Drug: Placebo to mycophenolate sodium

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Enteric-coated mycophenolate sodium (EC-MPS)	Drug	Enteric-coated mycophenolate sodium supplied as 180 mg tablets.	Enteric-coated mycophenolate sodium

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The Number of Participants Who Responded to the Conversion to Mycophenolate Sodium (EC-MPS) Therapy	Response assessed using the Gastrointestinal Symptom Rating Scale (GSRS), designed to assess common symptoms with gastrointestinal (GI) disorders. The GSRS has 5 subscales (reflux, diarrhea, constipation, abdominal pain and indigestion) producing a mean subscale score ranging from 1 (no discomfort) to 7 (very severe discomfort). The total score is an average of scores across all 15 items; a higher score indicates more GI symptoms. Response was defined as Day 30 improvement in the GSRS Total Score (change from baseline) of greater than or equal to 0.3. Minimum score is 1; maximum score is 7.	Baseline, Day 30

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Biopsy-proven Acute Rejection (BPAR) and Treated Acute Rejection (TAR)	TAR was defined as an episode of acute rejection that was suspected on clinical grounds and was treated and confirmed by the investigator according to the patient's response to therapy. BPAR was defined a treated acute rejection that was confirmed by biopsy. A graft core biopsy was performed before or within 24 hours of initiation of anti-rejection therapy and was assessed by the pathologist at the center according to the BANFF 1997 criteria.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Males and females aged 18-75 years, Recipients of first or second cadaveric, living unrelated or living related kidney transplant
Recipients who are at least 4 weeks post renal transplantation with stable renal function, Patients currently receiving MMF (all dosages are allowed) and either cyclosporine USP (MODIFIED) or tacrolimus with or without corticosteroids as part of their immunosuppressive regimen for at least 2 weeks prior to study start
Patients with at least one mild and/or moderate and/or severe upper or lower gastrointestinal (GI) complaints clearly associated with MMF therapy as determined by the treating physician. Additional mild GI complaints may coexist
Patients' immunosuppressive regimen other than steroids (doses and type) as well as medication for treatment of GI symptoms must be unchanged for at least 1 week prior to study start
Females of childbearing potential must have a negative pregnancy test prior to the inclusion period. The test should be performed locally at Baseline visit. If positive, the patient will not be included. Effective contraception must be used during the trial, and for 4 weeks following discontinuation of the study medication
Patients who are willing and able to participate in the full course of the study and from whom written informed consent has been obtained.

Exclusion criteria:

Multi-organ transplant patients (e.g. kidney and pancreas) or previous transplant with any other organ different from kidney (second kidney transplant is allowed)
History of GI disorder (diarrhea, Gastroesophageal Reflux Disease (GERD), dyspepsia, Inflammatory Bowel Disease (IBD) or Irritable Bowel Syndrome (IBS) prior to transplantation
Evidence of any GI disorder induced by an infection, underlying medical condition, or concomitant medication other than MMF, Modification of GI medication or MMF dose within last 1 week
Evidence of graft rejection, treatment of acute rejection, or unstable renal function within 4 weeks prior to the Baseline visit, Patients who have received an investigational immunosuppressive drug within 4 weeks prior to study entry
Patients with a history of malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin
Pregnant or nursing (lactating) women, Women of child-bearing potential (WOCBP) not using an acceptable method of contraception such as: surgical sterilization, hormonal contraception, or double-barrier methods.
Contraception should be maintained throughout the study and for 4 weeks after study drug discontinuation.

Other protocol defined inclusion/exclusion criteria may apply.

Contacts/Locations Module

Name	Affiliation	Role
Novartis	Novartis	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
AKDHC Medical Research Services, LLC		Phoenix	Arizona	85012	United States
University of Southern California

References Module

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IPD Sharing Statement Module

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Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Enteric-coated Mycophenolate Sodium	Enteric-coated mycophenolate sodium tablets taken orally twice a day (in the morning and in the evening) at a dose equimolar to the dose of mycophenolate mofetil the participant was taking prior to start of the study + Placebo to mycophenolate mofetil capsules taken orally twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

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No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

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No data is available for this block.

Condition Browse Module

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No data is available for this block.

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Enteric-coated Mycophenolate Sodium	Enteric-coated mycophenolate sodium tablets taken orally twice a day (in the morning and in the evening) at a dose equimolar to the dose of mycophenolate mofetil the participant was taking prior to start of the study + Placebo to mycophenolate mofetil capsules taken orally twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.
BG001	Mycophenolate Mofetil	Mycophenolate mofetil capsules taken orally twice a day (in the morning and in the evening) at the dose the participant was taking prior to study start + Placebo to mycophenolate sodium tablets taken twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Baseline Measures are based on the Intent-to-Treat (ITT) population that consisted of all randomized participants who received study drug.

Mean

Standard Deviation

Years

Title

Denominators

Categories

Response

Title	Measurements
	OG000123 OG001109

No Response

Title	Measurements
	OG000

Secondary

Number of Participants With Biopsy-proven Acute Rejection (BPAR) and Treated Acute Rejection (TAR)

TAR was defined as an episode of acute rejection that was suspected on clinical grounds and was treated and confirmed by the investigator according to the patient's response to therapy.

BPAR was defined a treated acute rejection that was confirmed by biopsy. A graft core biopsy was performed before or within 24 hours of initiation of anti-rejection therapy and was assessed by the pathologist at the center according to the BANFF 1997 criteria.

Intent-to-treat population consisted of all randomized participants who received at least one dose of study drug.

Posted

Number

Participants

30 days

ID	Title	Description
OG000	Enteric-coated Mycophenolate Sodium	Enteric-coated mycophenolate sodium tablets taken orally twice a day (in the morning and in the evening) at a dose equimolar to the dose of mycophenolate mofetil the participant was taking prior to start of the study + Placebo to mycophenolate mofetil capsules taken orally twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.
OG001	Mycophenolate Mofetil	Mycophenolate mofetil capsules taken orally twice a day (in the morning and in the evening) at the dose the participant was taking prior to study start + Placebo to mycophenolate sodium tablets taken twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.

Secondary

Change From Baseline to Day 30 in the Severity of Gastrointestinal Symptoms Overall Total Score

The Severity Score for each GI symptom for each participant was calculated based on the physician's evaluation of current GI symptoms recorded at Baseline and Day 30. For each of the 16 individual GI symptoms the severity score ranged from 0 (absent) to 3 (severe). The Overall Total Score is the Mean of severity ratings of the 16 individual symptoms.

Intention to treat (ITT) population consisted of all randomized participants who received at least one dose of study drug. "n" in each of the categories is the number of participants with data.

Posted

Mean

Standard Deviation

Score on a scale

Baseline, Day 30

ID	Title	Description
OG000	Enteric-coated Mycophenolate Sodium	Enteric-coated mycophenolate sodium tablets taken orally twice a day (in the morning and in the evening) at a dose equimolar to the dose of mycophenolate mofetil the participant was taking prior to start of the study + Placebo to mycophenolate mofetil capsules taken orally twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.
OG001	Mycophenolate Mofetil	Mycophenolate mofetil capsules taken orally twice a day (in the morning and in the evening) at the dose the participant was taking prior to study start + Placebo to mycophenolate sodium tablets taken twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.

Secondary

Number of Participants With Reported Dose Changes or Interruption of Study Medication During the 30 Days of Treatment

The number of participants with reported dose changes or interruption of study medication during the 30 days of treatment.The most common dose adjustments were dose increases back to baseline levels following a decrease or interruption and decreases due to abnormal laboratory value Adverse Events (leucopenia, thrombocytopenia, neutropenia, or anemia).

Intention to treat (ITT) population consisted of all randomized participants who received at least one dose of study drug.

Posted

Number

Participants

30 days

ID	Title	Description
OG000	Enteric-coated Mycophenolate Sodium	Enteric-coated mycophenolate sodium tablets taken orally twice a day (in the morning and in the evening) at a dose equimolar to the dose of mycophenolate mofetil the participant was taking prior to start of the study + Placebo to mycophenolate mofetil capsules taken orally twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.
OG001	Mycophenolate Mofetil	Mycophenolate mofetil capsules taken orally twice a day (in the morning and in the evening) at the dose the participant was taking prior to study start + Placebo to mycophenolate sodium tablets taken twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.

Secondary

Change From Baseline in Lower and Upper GI Symptom Burden Measured by GI Symptom Rating Scale Score

This is reflected by the total score. The total score incorporates lower and upper GI elements. GSRS overall score is the mean of 15 individual GI symptom scores, each rated on a 7- point scale: 1 = no discomfort, 2= minor discomfort, 3 = mild discomfort, 4 = moderate discomfort, 5 = moderately sever discomfort, 6 = severe discomfort and 7 = very severe discomfort. Change from Baseline was calculated using ANCOVA, model includes GSRS, center and treatment group.

Posted

Mean

Standard Deviation

change in score on a scale

Baseline, Day 30

ID	Title	Description
OG000	Enteric-coated Mycophenolate Sodium	Enteric-coated mycophenolate sodium tablets taken orally twice a day (in the morning and in the evening) at a dose equimolar to the dose of mycophenolate mofetil the participant was taking prior to start of the study + Placebo to mycophenolate mofetil capsules taken orally twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.
OG001	Mycophenolate Mofetil

Secondary

Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment

The GSRS has five subscales (reflux, diarrhea, constipation, abdominal pain, indigestion) producing a mean subscale score ranging from 1 (=no discomfort at all) to 7 (very severe discomfort). The mean score at baseline (BL), the mean score at Day 30 and the mean Change from BL to Day 30 is presented for each of the five subscales.

Posted

Mean

Standard Deviation

Score on a scale

Baseline to Day 30

ID	Title	Description
OG000	Enteric-coated Mycophenolate Sodium	Enteric-coated mycophenolate sodium tablets taken orally twice a day (in the morning and in the evening) at a dose equimolar to the dose of mycophenolate mofetil the participant was taking prior to start of the study + Placebo to mycophenolate mofetil capsules taken orally twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.
OG001	Mycophenolate Mofetil	Mycophenolate mofetil capsules taken orally twice a day (in the morning and in the evening) at the dose the participant was taking prior to study start + Placebo to mycophenolate sodium tablets taken twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.

Secondary

Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores

The GIQLI is a 36-item questionnaire to assess the impact of GI disease on daily life. The GIQLI has 5 different subscales (GI symptoms, emotional status, physical and social functions, and stress of medical treatment) that are rated on a 5-point scale from 0 to 4. The individual scores are summed to produce a total score of the 36 items for a total possible score of 0 to 144. Lower scores represent greater dysfunction.

Participants from the Intention-to-treat (ITT) population consisting of all randomized participants who received at least one dose of study drug for whom data was available for analysis. "n" in each of the categories is the number of participants with data available.

Posted

Mean

Standard Deviation

Score on a scale

Baseline, Day 30

ID	Title	Description
OG000	Enteric-coated Mycophenolate Sodium	Enteric-coated mycophenolate sodium tablets taken orally twice a day (in the morning and in the evening) at a dose equimolar to the dose of mycophenolate mofetil the participant was taking prior to start of the study + Placebo to mycophenolate mofetil capsules taken orally twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.
OG001	Mycophenolate Mofetil

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Enteric-coated Mycophenolate Sodium	Enteric-coated mycophenolate sodium tablets taken orally twice a day (in the morning and in the evening) at a dose equimolar to the dose of mycophenolate mofetil the participant was taking prior to start of the study + Placebo to mycophenolate mofetil capsules taken orally twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.			7	199	75	199
EG001	Mycophenolate Mofetil	Mycophenolate mofetil capsules taken orally twice a day (in the morning and in the evening) at the dose the participant was taking prior to study start + Placebo to mycophenolate sodium tablets taken twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.			11	197	89	197

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Angina unstable	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0012 affected197 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0012 affected197 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0012 affected197 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0010 affected197 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0012 affected197 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0012 affected197 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0010 affected197 at risk
Cytomegalovirus infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0011 affected197 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0010 affected197 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0010 affected197 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Skull fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Therapeutic agent toxicity	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0011 affected197 at risk
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0011 affected197 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0010 affected197 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0010 affected197 at risk
Mental status changes	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Renal failure acute	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0011 affected197 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected199 at risk EG0012 affected197 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0010 affected197 at risk
Lymphocele	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected199 at risk EG0010 affected197 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal distension	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00027 affected199 at risk EG00131 affected197 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00010 affected199 at risk EG00112 affected197 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0009 affected199 at risk EG00116 affected197 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0007 affected199 at risk EG00115 affected197 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00021 affected199 at risk EG00117 affected197 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00019 affected199 at risk EG00117 affected197 at risk
Eructation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0009 affected199 at risk EG00120 affected197 at risk
Flatulence	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00011 affected199 at risk EG00119 affected197 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00013 affected199 at risk EG0019 affected197 at risk
Intestinal functional disorder	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00010 affected199 at risk EG00114 affected197 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00011 affected199 at risk EG00121 affected197 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00010 affected199 at risk EG00114 affected197 at risk

ID	Term
D009173	Mycophenolic Acid

Mycophenolate mofetil capsules taken orally twice a day (in the morning and in the evening) at the dose the participant was taking prior to study start + Placebo to mycophenolate sodium tablets taken twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.

ID	Term
D002208	Caproates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D005227	Fatty Acids
D008055	Lipids