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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-010562-31 | EudraCT Number |
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Slow recruitment and lack of time to product launch
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| Name | Class |
|---|---|
| Parexel | INDUSTRY |
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The purpose of the study is to further investigate how much of the drug substance "mycophenolate mofetil" can be found in the blood of patients with kidney or renal transplants when treated with Myfenax® or CellCept®. Additionally, the safety and side effects of the two products will be compared. All information already available on these products indicates that the safety profiles of the two products will be the same.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Reference/Test/Test | Experimental | The reference product was CellCept® and test product was Myfenax®. In period I, participants received CellCept on Days 1-14. In period II, participants crossed-over to receive Myfenax on Days 15-28. In period III, participants received Myfenax until the end of the study (Days 29-112). Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening. |
|
| Test/Reference/Reference | Experimental | The test product was Myfenax® and the reference product was CellCept®. In period I, participants received Myfenax on Days 1-14. In period II, participants crossed-over to receive CellCept on Days 15-28. In period III, participants received CellCept until the end of the study (Days 29-112). Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| mycophenolate mofetil (Myfenax) | Drug | Each participant received at least 500 mg orally, twice daily (morning and evening) during those study periods labeled as 'T' (test drug). Participants receive the dose equivalent to the pre-study dose (within the recommended therapeutic range) of mycophenolate mofetil. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-time Curve (AUC(0-6h)) of Mycophenolate Mofetil | Area under the plasma concentration-time curve during a dosage interval at steady state (calculated using the trapezoidal rule, from t = 0 to t = 6 hours). | Day 14 and Day 28 (end of first two cross-over periods) before drug administration and at 30 min, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after drug administration |
| Area Under the Plasma Concentration-time Curve (AUC(0-tau)) of Mycophenolate Mofetil | For participants with a 0-12h profile: Area under the plasma concentration-time curve during a dosage interval at steady state (calculated using the trapezoidal rule, from t = 0 to t = 12 hours). For participants with a 0-6h profile: AUC(0-tau) was calculated based on AUC(0-6h) using the extrapolation formula according to Fleming. | Day 14 and Day 28 (end of first two cross-over periods) before drug administration and at 30 min, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after drug administration |
| Maximum Observed Plasma Concentration (Cmax) of Mycophenolate Mofetil | Cmax was directly obtained from measured values of plasma concentrations. | Day 14 and Day 28 (end of first two cross-over periods) before drug administration and at 30 min, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Minimum Observed Plasma Concentration (Cmin) of Mycophenolate Mofetil | Cmin was directly obtained from measured values of plasma concentrations. | Day 14 and Day 28 (end of first two cross-over periods) before drug administration and at 30 min, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after drug administration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gere Sunder-Plassman, Prof.,MD | Medical University Vienna | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | Sunder-Plassmann G et al.: Results of a Comparative Bioavailability Study of Myfenax (Teva) and CellCept (Roche) in Stable Kidney Transplant Recipients. American Transplant Congress 2011. Abstract Number: 250308 | ||
| 22500920 | Result | Sunder-Plassmann G, Reinke P, Rath T, Wiecek A, Nowicki M, Moore R, Lutz J, Gaggl M, Ferkl M. Comparative pharmacokinetic study of two mycophenolate mofetil formulations in stable kidney transplant recipients. Transpl Int. 2012 Jun;25(6):680-6. doi: 10.1111/j.1432-2277.2012.01475.x. Epub 2012 Apr 16. |
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A total of 100 subjects were planned. A total of 47 subjects were screened in the study. Four subjects were not randomised, i.e., two subjects withdrew consent, one subject had a protocol violation, and one subject was a screening failure (did not meet eligibility criteria).
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| ID | Title | Description |
|---|---|---|
| FG000 | Reference/Test/Test | The reference product was CellCept® and test product was Myfenax®. In period I, participants received CellCept on Days 1-14. In period II, participants crossed-over to receive Myfenax on Days 15-28. In period III, participants received Myfenax until the end of the study (Days 29-112). Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening. |
| FG001 | Test/Reference/Reference | The test product was Myfenax® and the reference product was CellCept®. In period I, participants received Myfenax on Days 1-14. In period II, participants crossed-over to receive CellCept on Days 15-28. In period III, participants received CellCept until the end of the study (Days 29-112). Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period I (Days 1-14) |
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| Period II (Days 15-28) |
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| Period III (Days 29-112) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Reference/Test/Test | The reference product was CellCept® and test product was Myfenax®. In period I, participants received CellCept on Days 1-14. In period II, participants crossed-over to receive Myfenax on Days 15-28. In period III, participants received Myfenax until the end of the study (Days 29-112). Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration-time Curve (AUC(0-6h)) of Mycophenolate Mofetil | Area under the plasma concentration-time curve during a dosage interval at steady state (calculated using the trapezoidal rule, from t = 0 to t = 6 hours). | PK population. Two participants were excluded from the PK population: one dropped out of the study during the first period so had no PK samples. The other was omitted due to protocol violations. | Posted | Mean | Standard Deviation | hour* µg /ml | Day 14 and Day 28 (end of first two cross-over periods) before drug administration and at 30 min, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after drug administration |
|
Day 1 up to Day 112
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CellCept | Participants experience while on CellCept during any of the three study periods. Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 12.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
The study was designed to have a power of at least 80 % to show bioequivalence with 80 subjects. Only 43 subjects were included.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Clinical Research | Teva Branded Pharmaceutical Products, R&D Inc. | 215-591-3000 | ustevatrials@tevapharm.com |
| ID | Term |
|---|---|
| D009173 | Mycophenolic Acid |
| ID | Term |
|---|---|
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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|
|
| mycophenolate mofetil (Cellcept) | Drug | Each participant received at least 500 mg orally, twice daily (morning and evening) during those study periods labeled as 'R' (reference drug). Participants receive the dose equivalent to the pre-study dose (within the recommended therapeutic range) of mycophenolate mofetil. |
|
|
| Plasma Concentrations of Mycophenolate Mofetil in Pre-Administration Samples (Cpd) |
Cpd was directly obtained from measured values of plasma concentrations. |
| Day 14 and Day 28 (end of first two cross-over periods) before drug administration |
| Degree of Fluctuation of the Concentration Levels of Mycophenolate Mofetil Over One Dosing Interval (PTF) | PTF was calculated as: (Cmax-Cmin)/(AUCt/t)*100 | Day 14 and Day 28 (end of first two cross-over periods) before drug administration |
| Time Corresponding to Occurrence of Cmax (Tmax) of Mycophenolate Mofetil | Tmax was directly obtained from measured values. | Day 14 and Day 28 (end of first two cross-over periods) before drug administration |
| Summary of Participants With Adverse Events | Summary of adverse events across three study time periods. The on-treatment time frame spanned the time during which study drug was administered. Relation to study drug was assessed by the investigator. The Adverse Event count includes serious and non-serious AEs. A serious AE (SAE) was any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or congenital anomaly/birth defect or was an important medical event could have jeopardized the patient's safety or required medical or surgical intervention to prevent one of the outcomes listed above. Severity was measured on a three-point scale: mild, moderate, severe. | Day 1 up to Day 112 |
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| NOT COMPLETED |
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|
| BG001 | Test/Reference/Reference | The test product was Myfenax® and the reference product was CellCept®. In period I, participants received Myfenax on Days 1-14. In period II, participants crossed-over to receive CellCept on Days 15-28. In period III, participants received CellCept until the end of the study (Days 29-112). Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Height | Mean | Standard Deviation | meters |
|
| Weight | Mean | Standard Deviation | kilograms |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| OG001 | Myfenax | Timeframes in periods I and II when participants took Myfenax in this cross-over study. Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening. |
|
|
|
| Primary | Area Under the Plasma Concentration-time Curve (AUC(0-tau)) of Mycophenolate Mofetil | For participants with a 0-12h profile: Area under the plasma concentration-time curve during a dosage interval at steady state (calculated using the trapezoidal rule, from t = 0 to t = 12 hours). For participants with a 0-6h profile: AUC(0-tau) was calculated based on AUC(0-6h) using the extrapolation formula according to Fleming. | PK population. Two participants were excluded from the PK population: one dropped out of the study during the first period so had no PK samples. The other was omitted due to protocol violations. | Posted | Mean | Standard Deviation | hour* µg /ml | Day 14 and Day 28 (end of first two cross-over periods) before drug administration and at 30 min, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after drug administration |
|
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Mycophenolate Mofetil | Cmax was directly obtained from measured values of plasma concentrations. | PK population. Two participants were excluded from the PK population: one dropped out of the study during the first period so had no PK samples. The other was omitted due to protocol violations. | Posted | Mean | Standard Deviation | µg /ml | Day 14 and Day 28 (end of first two cross-over periods) before drug administration and at 30 min, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after drug administration |
|
|
|
|
| Secondary | Minimum Observed Plasma Concentration (Cmin) of Mycophenolate Mofetil | Cmin was directly obtained from measured values of plasma concentrations. | PK population. Two participants were excluded from the PK population: one dropped out of the study during the first period so had no PK samples. The other was omitted due to protocol violations. | Posted | Mean | Standard Deviation | µg /ml | Day 14 and Day 28 (end of first two cross-over periods) before drug administration and at 30 min, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after drug administration |
|
|
|
|
| Secondary | Plasma Concentrations of Mycophenolate Mofetil in Pre-Administration Samples (Cpd) | Cpd was directly obtained from measured values of plasma concentrations. | PK population. Two participants were excluded from the PK population: one dropped out of the study during the first period so had no PK samples. The other was omitted due to protocol violations. | Posted | Mean | Standard Deviation | µg /ml | Day 14 and Day 28 (end of first two cross-over periods) before drug administration |
|
|
|
| Secondary | Degree of Fluctuation of the Concentration Levels of Mycophenolate Mofetil Over One Dosing Interval (PTF) | PTF was calculated as: (Cmax-Cmin)/(AUCt/t)*100 | PK population. Two participants were excluded from the PK population: one dropped out of the study during the first period so had no PK samples. The other was omitted due to protocol violations. | Posted | Mean | Standard Deviation | percentage of AUC for a dosing interval | Day 14 and Day 28 (end of first two cross-over periods) before drug administration |
|
|
|
| Secondary | Time Corresponding to Occurrence of Cmax (Tmax) of Mycophenolate Mofetil | Tmax was directly obtained from measured values. | PK population. Two participants were excluded from the PK population: one dropped out of the study during the first period so had no PK samples. The other was omitted due to protocol violations. | Posted | Mean | Standard Deviation | hours | Day 14 and Day 28 (end of first two cross-over periods) before drug administration |
|
|
|
| Secondary | Summary of Participants With Adverse Events | Summary of adverse events across three study time periods. The on-treatment time frame spanned the time during which study drug was administered. Relation to study drug was assessed by the investigator. The Adverse Event count includes serious and non-serious AEs. A serious AE (SAE) was any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or congenital anomaly/birth defect or was an important medical event could have jeopardized the patient's safety or required medical or surgical intervention to prevent one of the outcomes listed above. Severity was measured on a three-point scale: mild, moderate, severe. | Safety population. One participant discontinued the study prior to Period II so the Myfenax # participants analyzed is one less than the CellCept arm. | Posted | Number | participants | Day 1 up to Day 112 |
|
|
|
| 1 |
| 43 |
| 15 |
| 43 |
| EG001 | Myfenax | Participants experience while on Myfenax during any of the three study periods. Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening. | 1 | 42 | 16 | 42 |
| EG002 | Overall | Participant experience overall, i.e. all treatment experiences while on study are included | 1 | 43 | 26 | 43 |
| Cardiac failure | Cardiac disorders | MedDRA 12.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 12.1 | Systematic Assessment |
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| Herpes simplex | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA 12.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
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| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 12.1 | Systematic Assessment |
|
| Conjunctivitis allergic | Eye disorders | MedDRA 12.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Periodontitis | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Rectal discharge | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Application site erythema | General disorders | MedDRA 12.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 12.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 12.1 | Systematic Assessment |
|
| Joint injury | Injury, poisoning and procedural complications | MedDRA 12.1 | Systematic Assessment |
|
| Ulna fracture | Injury, poisoning and procedural complications | MedDRA 12.1 | Systematic Assessment |
|
| Blood triglycerides increased | Investigations | MedDRA 12.1 | Systematic Assessment |
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| Cardiac murmur | Investigations | MedDRA 12.1 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 12.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
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| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Bowenoid papulosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.1 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA 12.1 | Systematic Assessment |
|
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 12.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 12.1 | Systematic Assessment |
|
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
| D005227 |
| Fatty Acids |
| D008055 | Lipids |
| Title | Measurements |
|---|---|
|
| Severe adverse events |
|
| Adverse events leading to discontinuation |
|
| Serious adverse events |
|
| Adverse events leading to death |
|