Trial Outcomes & Findings for Enteric-Coated Mycophenolate Sodium on Quality of Life in Patients With Gastrointestinal Symptoms Related to Mycophenolate Mofetil Therapy After Kidney Transplantation (NCT NCT00239005)

Last Updated: 2017-03-30

Results Overview

The primary assessment was based on the percentage of patients who were maintained at week 13 on a dose at least one dose equivalent greater than at baseline (visit 2/week 1). A dose equivalent was defined as EC-MPS 180 mg/day or MMF 250 mg/day.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

134 participants

Primary outcome timeframe

at week 13 (last visit)

Results posted on

2017-03-30

Participant Flow

In total, 135 patients were screened. One patient was not randomized due to an SAE prior to the randomization visit. Out of 134 randomized patients, 5 withdrew before taking study drug. Analysis population: 68 in EC-MPS, 61 in MMF.

Participant milestones

Participant milestones
Measure	Enteric-Coated Mycophenolate Sodium (EC-MPS) Oral film-coated gastroresistant tablets containing 360mg or 180mg of mycophenolate sodium. Daily dose decided by the physician, was taken morning and evening.	Mycophenolate Mofetil (MMF) 250 mg capsules or 500 mg tablets of mycophenolate mofetil. Daily dose decided by physician, was taken morning and evening.
Overall Study STARTED	69	65
Overall Study Intention-to-treat Population (ITT)	68	61
Overall Study COMPLETED	57	53
Overall Study NOT COMPLETED	12	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Enteric-Coated Mycophenolate Sodium (EC-MPS) Oral film-coated gastroresistant tablets containing 360mg or 180mg of mycophenolate sodium. Daily dose decided by the physician, was taken morning and evening.	Mycophenolate Mofetil (MMF) 250 mg capsules or 500 mg tablets of mycophenolate mofetil. Daily dose decided by physician, was taken morning and evening.
Overall Study Adverse Event	6	6
Overall Study Withdrawal by Subject	3	4
Overall Study Unsatisfactory Therapeutic effect	2	0
Overall Study Protocol Violation	1	0
Overall Study Subj. cond. no longer needs study drug	0	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Enteric-Coated Mycophenolate Sodium on Quality of Life in Patients With Gastrointestinal Symptoms Related to Mycophenolate Mofetil Therapy After Kidney Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Enteric-Coated Mycophenolate Sodium (EC-MPS) n=68 Participants Oral film-coated gastroresistant tablets containing 360mg or 180mg of mycophenolate sodium. Daily dose decided by the physician, was taken morning and evening.	Mycophenolate Mofetil (MMF) n=61 Participants 250 mg capsules or 500 mg tablets of mycophenolate mofetil. Daily dose decided by physician, was taken morning and evening.	Total n=129 Participants Total of all reporting groups
Age, Customized <65 years	65 participants n=5 Participants	51 participants n=7 Participants	116 participants n=5 Participants
Age, Customized >=65 years	3 participants n=5 Participants	10 participants n=7 Participants	13 participants n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	25 Participants n=7 Participants	56 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	36 Participants n=7 Participants	73 Participants n=5 Participants

PRIMARY outcome

Timeframe: at week 13 (last visit)

Population: The intent-to-treat (ITT) population consisted of all randomized patients who provided baseline and at least 1 post-baseline assessment of the primary variable.

Outcome measures

Outcome measures
Measure	Enteric-Coated Mycophenolate Sodium (EC-MPS) n=68 Participants Oral film-coated gastroresistant tablets containing 360mg or 180mg of mycophenolate sodium. Daily dose decided by the physician, was taken morning and evening.	Mycophenolate Mofetil (MMF) n=61 Participants 250 mg capsules or 500 mg tablets of mycophenolate mofetil. Daily dose decided by physician, was taken morning and evening.
Mycophenolic Acid (MPA) Maintenance Treatment	47.06 Percentage of Patients Interval 34.83 to 59.55	16.39 Percentage of Patients Interval 8.15 to 28.09

SECONDARY outcome

Timeframe: At week 3 and week 13 (last visit)

Population: Intention to treat (ITT) population consisted of all randomized patients who provided baseline and at least 1 post-baseline assessment of the primary variable. In this analysis patients who completed GSRS questionnaire in visit 2 (week 1), visit 3 (week 3) and visit 4 (week 13) were included.

The GSRS is a 15-item instrument designed to assess the impact of upper and lower GI symptoms. There are five subscales: reflux, diarrhea, constipation, abdominal pain, and indigestion-each of which produces a mean subscale score ranging from 1 (no discomfort) to 7 (very severe discomfort). A higher score represents greater impairment of quality of life due to GI symptoms (range from 1 to 7).

Outcome measures

Outcome measures
Measure	Enteric-Coated Mycophenolate Sodium (EC-MPS) n=61 Participants Oral film-coated gastroresistant tablets containing 360mg or 180mg of mycophenolate sodium. Daily dose decided by the physician, was taken morning and evening.	Mycophenolate Mofetil (MMF) n=59 Participants 250 mg capsules or 500 mg tablets of mycophenolate mofetil. Daily dose decided by physician, was taken morning and evening.
Changes in Gastrointestinal (GI) Symptoms as Measured by the Gastrointestinal Symptom Rating Scale (GSRS). Week 3: change in GSRS Total Score (N= 61, 59)	-0.63 Units on a scale Standard Error 0.139	-0.32 Units on a scale Standard Error 0.142
Changes in Gastrointestinal (GI) Symptoms as Measured by the Gastrointestinal Symptom Rating Scale (GSRS). Week 13: change in GSRS Total Score (N= 60, 56)	-0.44 Units on a scale Standard Error 0.165	-0.25 Units on a scale Standard Error 0.169

SECONDARY outcome

Timeframe: At week 3 and week 13 (last visit)

Population: Intention to treat (ITT) population consisted of all randomized patients who provided baseline and at least 1 post-baseline assessment of the primary variable. In this analysis patients who completed GIQLI questionnaire in visit 2 (week 1), visit 3 (week 3) and visit 4 (week 13) were included.

Health-related quality of life (HRQoL)was assessed by the Gastrointestinal Quality of Life Index (GIQLI). The GIQLI is a 36-item questionnaire to assess the impact of GI disease on daily life. The GIQLI also has five different subscales (GI symptoms, emotional status, physical and social functions, and stress of medical treatment) producing a total score of the 36 items. Lower scores represent more dysfunction. A higher score represents a better quality of life (range from 0 to 144).

Outcome measures

Outcome measures
Measure	Enteric-Coated Mycophenolate Sodium (EC-MPS) n=61 Participants Oral film-coated gastroresistant tablets containing 360mg or 180mg of mycophenolate sodium. Daily dose decided by the physician, was taken morning and evening.	Mycophenolate Mofetil (MMF) n=58 Participants 250 mg capsules or 500 mg tablets of mycophenolate mofetil. Daily dose decided by physician, was taken morning and evening.
Changes in Gastrointestinal Symptoms as Measured by the Gastrointestinal Quality of Life Index (GIQLI). Week 13: change in GIQLI Total Score (N= 60, 56)	4.84 Units on a scale Standard Error 4.331	1.77 Units on a scale Standard Error 4.458
Changes in Gastrointestinal Symptoms as Measured by the Gastrointestinal Quality of Life Index (GIQLI). Week 3: change in GIQLI Total Score (N= 61, 58)	11.65 Units on a scale Standard Error 3.470	6.08 Units on a scale Standard Error 3.549

Adverse Events

Enteric-Coated Mycophenolate Sodium (EC-MPS)

Serious events: 9 serious events

Other events: 25 other events

Deaths: 0 deaths

Mycophenolate Mofetil (MMF)

Serious events: 7 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Enteric-Coated Mycophenolate Sodium (EC-MPS) n=68 participants at risk Oral film-coated gastroresistant tablets containing 360mg or 180mg of mycophenolate sodium. Daily dose decided by the physician, was taken morning and evening.	Mycophenolate Mofetil (MMF) n=61 participants at risk 250 mg capsules or 500 mg tablets of mycophenolate mofetil. Daily dose decided by physician, was taken morning and evening.
Gastrointestinal disorders Abdominal pain	5.9% 4/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Gastrointestinal disorders Diarrhoea	17.6% 12/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	19.7% 12/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Gastrointestinal disorders Dyspepsia	4.4% 3/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	8.2% 5/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Gastrointestinal disorders Nausea	4.4% 3/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	6.6% 4/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Gastrointestinal disorders Vomiting	7.4% 5/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	6.6% 4/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Infections and infestations Lower respiratory tract infection	2.9% 2/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	6.6% 4/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Infections and infestations Nasopharyngitis	5.9% 4/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	6.6% 4/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Infections and infestations Urinary tract infection	2.9% 2/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	6.6% 4/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Nervous system disorders Headache	5.9% 4/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Enteric-Coated Mycophenolate Sodium (EC-MPS) n=68 participants at risk Oral film-coated gastroresistant tablets containing 360mg or 180mg of mycophenolate sodium. Daily dose decided by the physician, was taken morning and evening.	Mycophenolate Mofetil (MMF) n=61 participants at risk 250 mg capsules or 500 mg tablets of mycophenolate mofetil. Daily dose decided by physician, was taken morning and evening.
Blood and lymphatic system disorders Anaemia	0.00% 0/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Cardiac disorders Cardiac failure congestive	1.5% 1/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	0.00% 0/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Gastrointestinal disorders Diarrhoea	1.5% 1/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Gastrointestinal disorders Gastritis	0.00% 0/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Gastrointestinal disorders Nausea	1.5% 1/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Gastrointestinal disorders Vomiting	1.5% 1/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	0.00% 0/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
General disorders Chest pain	0.00% 0/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
General disorders Chills	0.00% 0/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
General disorders Pyrexia	4.4% 3/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	0.00% 0/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Infections and infestations Cytomegalovirus infection	1.5% 1/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	0.00% 0/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Infections and infestations Lower respiratory tract infection	0.00% 0/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Infections and infestations Pneumonia	1.5% 1/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	0.00% 0/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Infections and infestations Sepsis	0.00% 0/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	3.3% 2/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Infections and infestations Urinary tract infection	2.9% 2/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Injury, poisoning and procedural complications Complications of transplanted kidney	1.5% 1/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	0.00% 0/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Investigations Blood creatinine increased	1.5% 1/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	0.00% 0/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Dehydration	0.00% 0/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hyperkalaemia	1.5% 1/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	1.5% 1/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	0.00% 0/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Nervous system disorders Headache	0.00% 0/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Renal and urinary disorders Renal failure acute	1.5% 1/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	0.00% 0/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.
Vascular disorders Aortic dissection	0.00% 0/68 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.	1.6% 1/61 • 13 weeks The Safety population consisted of all randomized patients who had at least one post-baseline safety assessment.