Measurement of Gastrointestinal (GI) and Health-related Quality of Life (HRQL) Outcomes in Liver Transplant Recipients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00405652
• Collaborator: (none)
• Enrollment: 34
• Location: 1
• Arm: 1
• Duration (Months): 20
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

Treatment with the immunosuppressive drug mycophenolate mofetil (MMF) may result in gastrointestinal (GI) complications in some patients. This study will assess if a switch from MMF to enteric-coated mycophenolate sodium (EC-MPS) results in improved GI and/or health-related quality of life in liver transplant recipients

Condition or Disease	Intervention/Treatment	Phase
Liver Transplantation	Drug: Enteric-coated Mycophenolate sodium (EC-MPS)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Measurement of Patient Reported Gastrointestinal (GI) and Health-related Quality of Life (HRQL) Outcomes in Liver Transplant Recipients (MyLiver)
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Enteric-coated Mycophenolate sodium Enteric-coated Mycophenolate sodium (EC-MPS), administered orally twice a day to achieve a dose equimolar to the dose of Mycophenolate mofetil (MMF) the patient was taking at the time of study entry up to a maximum dose of 1440 mg.	Drug: Enteric-coated Mycophenolate sodium (EC-MPS); experimental; Other Names: myfortic

Outcome Measures

Primary Outcome Measures

1. Changes in Gastrointestinal Symptom Severity and Health Related Quality of Life [Baseline, End of Study (6-8 weeks)]

   Change in Gastrointestinal symptom rating scale (GSRS) total score from baseline visit to follow-up visit 6-8 weeks after treatment. 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 GSRS total score was computed by the mean of the subscale scores.

Secondary Outcome Measures

1. The Number of Participants With Subclinical Rejection as Evaluated by a Change in Liver Enzymes [12-20 weeks]

   The number of participants with subclinical rejection episodes as defined by a steroid-sensitive, clinically relevant increase of AST, ALT, gamma-GT, AP or bilirubin (i.e., elevation of one or more of these enzymes that was considered clinically relevant and showed resolution upon treatment with a slight increase of steroid dosage).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Received liver transplant at least 3 months prior to study enrollment.

• Receiving immunosuppressive regimen that includes a calcineurin or mTOR inhibitor, and MMF at time of study enrolment. The patient must be stable on current immunosuppressive regimen. The MMF dose must be stable for at least 1 month prior to enrollment. Steroid use will be according to local practice.

• Patients can only be enrolled into the study if it is expected that treatment will continue at the same dose until study end (6-8 weeks after enrollment).

• Patients with a medical condition that necessitates MPA-treatment for probably the next 6- 8 weeks (time of study duration).

• Patients with at least mild overall Gastrointestinal (G)I complications as assessed by the GI complications Case Report Form(CRF).

• Eligible and willing to convert to Myfortic.

• At lease 18 years of age.

• Willing to provide written informed consent.

• Able to meet all study requirements including completing the questionnaires and completing 2 study visits.

• Patients receiving drugs that may cause GI symptoms such as bisphosphonates, minerals, vitamins, antibiotics or proton pump inhibitors (PPIs) have to be on a stable dose of these substances for at least 1 month prior to enrollment. Patients receiving these drugs can only be enrolled into the study, if it is expected that treatment will continue at the same dose until study end (6-8 weeks after enrollment).

• Females capable of becoming pregnant must have a negative pregnancy test within 7 days prior to or at baseline. Pregnancy test has to be repeated every 4 weeks. Females are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility.

Exclusion criteria:

• If applicable, GI symptoms assumed or know not to be caused by MPA therapy (e.g. oral bisphosphonates induced, infections diarrhea).

• Acute rejection <1 week prior to study enrollment

• Patients with Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and or/ bilirubin values >=3 x Upper limit normal (ULN) (values available from the last routine assessment within 3 months are acceptable).

• Patients with serum creatinine values >=265 umol/L (values available from the last routine assessment within 3 month are acceptable).

• Patients with hemoglobin values <7g/dL and/or an absolute platelet count of <50 x 10^{9/L and /or an absolute leukocytes count of <2.0 x10}9/L (values available from the last routine assessment within 3 month are acceptable.)

• Woman of child-bearing potential who is planning to become pregnant or is pregnant and/or lactating or who is unwilling to use effective means of contraception.

• Presence of psychiatric illness (i.e., schizophrenia, major depression) that, in the opinion of the site investigator, could interfere with study requirements.

• Undergoing acute medical intervention or hospitalization.

• Presence of a medical condition not related to a GI event at the time of visit, which requires immediate medical intervention.

• Any other medical condition that, in the opinion of the site investigator based on recall or chart review, interfere with completing the study, including but not limited to, visual problems or cognitive impairment.

• Receiving any investigational drug or have received any investigational drug within 30 days prior to study enrollment.

• Patients with hypersensitivity to mycophenolate sodium, mycophenolic acid, mycophenolic mofetil or other components of the formulation (e.g. lactose; see also SmPCs)

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Nuernberg		Germany

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00405652
• Other Study ID Numbers: CERL080ADE09
• First Posted: Nov 30, 2006
• Last Update Posted: Mar 3, 2011
• Last Verified: Feb 1, 2011

• Keywords provided by , ,: Liver transplantation, mycophenolate, GI problems, Quality of Life
• Additional relevant MeSH terms: Mycophenolic Acid

Study Results

Participant Flow

Arm/Group Title	Enteric-coated Mycophenolate Sodium
Arm/Group Description	Enteric-coated Mycophenolate sodium (EC-MPS), administered orally twice a day to achieve a dose equimolar to the dose of Mycophenolate mofetil (MMF) the patient was taking at the time of study entry up to a maximum dose of 1440 mg.
Period Title: Overall Study
STARTED	34
COMPLETED	30
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Enteric-coated Mycophenolate Sodium
Arm/Group Description	Enteric-coated Mycophenolate sodium (EC-MPS), administered orally twice a day to achieve a dose equimolar to the dose of Mycophenolate mofetil (MMF) the patient was taking at the time of study entry up to a maximum dose of 1440 mg.
Overall Participants	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.8 (9.6)
Sex: Female, Male (Count of Participants)
Female	14 41.2%
Male	20 58.8%

Outcome Measures

1. Primary Outcome

Title	Changes in Gastrointestinal Symptom Severity and Health Related Quality of Life
Description	Change in Gastrointestinal symptom rating scale (GSRS) total score from baseline visit to follow-up visit 6-8 weeks after treatment. 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 GSRS total score was computed by the mean of the subscale scores.
Time Frame	Baseline, End of Study (6-8 weeks)

Outcome Measure Data

Analysis Population Description

Intent to Treat Population (No last Observation Carried Forward). The number of participants completing the GSRS at Baseline = 31 and at the End of Study= 29.

Arm/Group Title	Enteric-coated Mycophenolate Sodium
Arm/Group Description	Enteric-coated Mycophenolate sodium (EC-MPS), administered orally twice a day to achieve a dose equimolar to the dose of Mycophenolate mofetil (MMF) the patient was taking at the time of study entry up to a maximum dose of 1440 mg.
Measure Participants	31
Baseline (Visit 1) n=31	2.88 (0.66)
End of Study (Visit 2) n=29	2.10 (0.78)

2. Secondary Outcome

Title	The Number of Participants With Subclinical Rejection as Evaluated by a Change in Liver Enzymes
Description	The number of participants with subclinical rejection episodes as defined by a steroid-sensitive, clinically relevant increase of AST, ALT, gamma-GT, AP or bilirubin (i.e., elevation of one or more of these enzymes that was considered clinically relevant and showed resolution upon treatment with a slight increase of steroid dosage).
Time Frame	12-20 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Enteric-coated Mycophenolate Sodium
Arm/Group Description	Enteric-coated Mycophenolate sodium (EC-MPS), administered orally twice a day to achieve a dose equimolar to the dose of Mycophenolate mofetil (MMF) the patient was taking at the time of study entry up to a maximum dose of 1440 mg.
Measure Participants	34
Number [Participants]	6 17.6%

Adverse Events

Arm/Group Title	Enteric-coated Mycophenolate Sodium
Arm/Group Description	Enteric-coated Mycophenolate sodium (EC-MPS), administered orally twice a day to achieve a dose equimolar to the dose of Mycophenolate mofetil (MMF) the patient was taking at the time of study entry up to a maximum dose of 1440 mg.
All Cause Mortality
	Enteric-coated Mycophenolate Sodium
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Enteric-coated Mycophenolate Sodium
	Affected / at Risk (%)	# Events
Total	4/34 (11.8%)
Gastrointestinal disorders
Faecaloma	1/34 (2.9%)
Infections and infestations
Hepatitis c	1/34 (2.9%)
Herpes zoster	1/34 (2.9%)
Injury, poisoning and procedural complications
Transplant failure	1/34 (2.9%)
Investigations
Alanine aminotransferase increased	1/34 (2.9%)
Aspartate aminotransferase increased	1/34 (2.9%)
Blood alkaline phosphatase increased	1/34 (2.9%)
Gamma-glutamyltransferase increased	1/34 (2.9%)
Glutamate dehydrogenase increased	1/34 (2.9%)
Psychiatric disorders
Alcoholism	1/34 (2.9%)
Renal and urinary disorders
Renal failure	1/34 (2.9%)
Skin and subcutaneous tissue disorders
Pruritus generalised	1/34 (2.9%)
Other (Not Including Serious) Adverse Events
	Enteric-coated Mycophenolate Sodium
	Affected / at Risk (%)	# Events
Total	23/34 (67.6%)
Gastrointestinal disorders
Abdominal distension	11/34 (32.4%)
Abdominal pain	7/34 (20.6%)
Constipation	3/34 (8.8%)
Diarrhoea	10/34 (29.4%)
Dyspepsia	3/34 (8.8%)
Nausea	5/34 (14.7%)
General disorders
Fatigue	2/34 (5.9%)
Feeling cold	2/34 (5.9%)
Infections and infestations
Nasopharyngitis	4/34 (11.8%)
Investigations
Alanine aminotransferase increased	2/34 (5.9%)
Blood alkaline phosphatase increased	2/34 (5.9%)
Blood bilirubin increased	3/34 (8.8%)
Gamma-glutamyltransferase increased	3/34 (8.8%)
Nervous system disorders
Headache	3/34 (8.8%)
Respiratory, thoracic and mediastinal disorders
Cough	2/34 (5.9%)
Skin and subcutaneous tissue disorders
Pruritus	2/34 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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 the pooled data (i.e., data from all sites) in the clinical trial.