Phase 3 N=68 Treatment

A Study of Mycophenolate Mofetil (CellCept) in Lung Transplant Recipients

Lung Transplantation

Bottom Line

View on ClinicalTrials.gov: NCT01014442 ↗

Enrolled (actual)

Serious AEs

39.7%

Results posted

Feb 2017

Primary outcome: Primary: Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4 — 7.914; 5.608; 117.210; 91.207 mg/L — p=0.2649

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: mycophenolate mofetil (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Hoffmann-La Roche
Primary completion: Jun 2012

Outcome Measures

Outcome	Result	p-value
PRIMARY Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4	7.914; 5.608; 117.210; 91.207; 1.583; 1.810	0.2649
PRIMARY Cmax of MPA, MPAG and AcMPAG at Day 8	5.124; 6.106; 100.127; 100.128; 1.007; 1.361	0.1308
PRIMARY Cmax of MPA, MPAG and AcMPAG at Day 20	5.284; 6.762; 93.882; 124.450; 0.624; 1.434	0.0886
PRIMARY Cmax of MPA, MPAG and AcMPAG at Day 90	12.915; 7.294; 104.938; 113.453; 1.375; 1.163	0.0318 sig
PRIMARY Cmax of Free MPA at Day 4	135.275; 84.014	0.3002
PRIMARY Cmax of Free MPA at Day 8	59.571; 95.553	0.0334 sig
PRIMARY Cmax of Free MPA at Day 20	51.822; 100.094	0.1151
PRIMARY Cmax of Free MPA at Day 90	87.293; 101.472	0.5974
PRIMARY Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 4	0.00557; 0.00422; 0.08286; 0.06749; 0.001122; 0.001388	0.5466
PRIMARY Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	0.00356; 0.00435; 0.06980; 0.07070; 0.000702; 0.000967	0.1511
PRIMARY Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	0.00395; 0.00456; 0.07044; 0.08430; 0.000482; 0.000969	0.3784
PRIMARY Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	0.01261; 0.00742; 0.10671; 0.10948; 0.001377; 0.001134	0.0509
PRIMARY Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4	1.823; 2.892; 3.713; 4.891; 2.379; 3.405	0.5745
PRIMARY Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	2.138; 1.659; 3.669; 3.647; 2.802; 2.546	0.8106
PRIMARY Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	2.293; 2.463; 3.762; 4.907; 2.842; 3.411	1.0000
PRIMARY Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	1.450; 2.143; 3.095; 4.420; 2.234; 3.564	0.8834
PRIMARY Minimum Concentration (Cmin) of MPA, MPAG and AcMPAG at Day 4	1.267; 1.094; 66.917; 47.493; 0.602; 0.733	0.5224
PRIMARY Cmin of MPA, MPAG and AcMPAG at Day 8	0.750; 0.772; 54.566; 57.189; 0.386; 0.517	0.4027
PRIMARY Cmin of MPA, MPAG and AcMPAG at Day 20	0.782; 1.234; 58.484; 69.023; 0.261; 0.528	0.0818
PRIMARY Cmin of MPA, MPAG and AcMPAG at Day 90	1.103; 1.570; 57.957; 80.488; 0.449; 0.466	0.3289
PRIMARY Cmin of Free MPA at Day 4	40.188; 23.711	0.4043
PRIMARY Cmin of Free MPA at Day 8	18.161; 15.669	0.8930
PRIMARY Cmin of Free MPA at Day 20	12.193; 20.237	0.0819
PRIMARY Cmin of Free MPA at Day 90	8.102; 18.831	0.0414 sig
PRIMARY Volume of Distribution (Vz) of MPA, MPAG and AcMPAG at Day 4	345.46; 287.74; 11.681; 12.062; 1065.02; 705.38	0.1552
PRIMARY Vz of MPA, MPAG and AcMPAG at Day 8	465.45; 331.51; 12.168; 12.740; 1432.88; 1173.38	0.0659
PRIMARY Vz of MPA, MPAG and AcMPAG at Day 20	476.06; 257.57; 12.798; 9.533; 3006.18; 1571.93	0.0040 sig
PRIMARY Vz of MPA, MPAG and AcMPAG at Day 90	139.48; 192.53; 9.254; 9.201; 811.15; 980.49	0.9029
PRIMARY Clearance (CL) of MPA, MPAG and AcMPAG at Day 4	68.471; 56.709; 1.6754; 1.7615; 206.60; 140.96	0.1362
PRIMARY CL of MPA, MPAG and AcMPAG at Day 8	90.921; 81.578; 2.3235; 1.7847; 410.86; 253.81	0.0572
PRIMARY CL of MPA, MPAG and AcMPAG at Day 20	83.068; 58.295; 1.9338; 1.4788; 680.68; 232.34	0.0048 sig
PRIMARY CL of MPA, MPAG and AcMPAG at Day 90	38.091; 36.922; 1.5701; 1.2433; 231.28; 223.56	0.9417
PRIMARY Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of MPA, MPAG and AcMPAG at Day 4	23.460; 27.174; 1095.98; 829.14; 10.414; 13.672	0.2798
PRIMARY AUC0-12 of MPA, MPAG and AcMPAG at Day 8	17.841; 23.352; 881.50; 888.96; 6.064; 9.081	0.0510
PRIMARY AUC0-12 of MPA, MPAG and AcMPAG at Day 20	18.925; 28.290; 812.65; 1095.37; 3.252; 9.482	0.0002 sig
PRIMARY AUC0-12 of MPA, MPAG and AcMPAG at Day 90	32.365; 31.864; 776.28; 972.69; 7.776; 7.219	0.7144
PRIMARY AUC0-12 of Free MPA at Day 4	135.703; 80.272	0.2342
PRIMARY AUC0-12 of Free MPA at Day 8	61.155; 83.683	0.1964
PRIMARY AUC0-12 of Free MPA at Day 20	48.530; 89.315	0.0672
PRIMARY AUC0-12 of Free MPA at Day 90	68.874; 99.212	0.2453
PRIMARY Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4	0.01652; 0.02016; 0.7720; 0.6165; 0.00739; 0.01056	0.1362
PRIMARY Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8	0.01256; 0.01624; 0.6157; 0.6270; 0.00426; 0.00644	0.0572
PRIMARY Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20	0.01402; 0.01923; 0.6059; 0.7440; 0.00239; 0.00642	0.0048 sig
PRIMARY Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90	0.03126; 0.03172; 0.7887; 0.9190; 0.00748; 0.00700	0.9417
PRIMARY Free Fraction of Free MPA at Day 4	0.5789; 0.3208	0.0821
PRIMARY Free Fraction of Free MPA at Day 8	0.3595; 0.3594	0.3628
PRIMARY Free Fraction of Free MPA at Day 20	0.2922; 0.3052	0.9873
PRIMARY Free Fraction of Free MPA at Day 90	0.2270; 0.3020	0.2178
SECONDARY Forced Expiratory Volume in 1 Second (FEV1) at Day 90 Post-Transplantation	3.087; 2.834	—
SECONDARY Percent of Predicted FEV1 at Day 90 Post-Transplantation	81.75; 90.17	—
SECONDARY Forced Vital Capacity (FVC) at Day 90 Post-Transplantation	3.445; 3.619	—
SECONDARY Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels	24.0; 85.4; 162.9; 144.9; -42.4; -45.9	—
SECONDARY Change From Baseline in T-Cell Phenotype	-1.34; -3.01; 1.74; -2.81; 3.29; 1.88	—
SECONDARY Percentage of Participants With Opportunistic Infections	18.2; 20.0	1.0000

Summary

This open-label, single center study will assess the pharmacokinetics, efficacy and safety of mycophenolate mofetil in lung allograft recipients. Participants will be split into 2 groups according to the original disease: Group A (cystic fibrosis) and Group B (chronic obstructive pulmonary disease [COPD], emphysema, idiopathic pulmonary fibrosis, alpha-1 antitrypsin deficiency [A1AD]). All participants will receive mycophenolate mofetil orally, 1.5 grams (g) twice daily (BID) from Day 2 to 30 post transplantation, and 1 g BID from Day 31 to 90 post transplantation. Anticipated time on study treatment is 90 days, and target sample size is 50-100 individuals.

Eligibility Criteria

Inclusion Criteria

primary single or bilateral lung allograft
original disease cystic fibrosis, COPD, emphysema, idiopathic pulmonary fibrosis or A1AD

Exclusion Criteria

lung allograft retransplantation
multiple organ transplantation
severe gastrointestinal disorder
malignancies or history of malignancy

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01014442). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.