RESUMO
OBJECTIVE: To evaluate the safety and efficacy of a novel microbial lipase (NM-BL) in a liquid formulation for the treatment of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis (CF) in a phase IIa proof-of-concept study. STUDY DESIGN: We conducted a double-blind, randomized, placebo controlled crossover study in patients with cystic fibrosis and exocrine pancreatic insufficiency. Adolescent and adult patients with CF were randomized to receive NM-BL or placebo for 1 week as replacement for their usual pancreatic enzyme formulation. They were subsequently crossed-over to the alternate study treatment. The coefficient of fat absorption was evaluated as the primary endpoint. Symptoms and adverse events were evaluated as secondary endpoints. RESULTS: A total of 35 patients were randomized into the study and 22 patients completed both treatment periods. During treatment with NM-BL, the coefficient of fat absorption was significantly greater (72.7%) compared with placebo (53.8%) with a difference between groups of 18.8% (P < .001). Subjective assessment of stool fat and stool consistency also improved under treatment with NM-BL. Adverse events were mostly gastrointestinal in nature and were more common in the group receiving NM-BL. CONCLUSIONS: Currently available pancreatic enzyme products are limited because of the lack of liquid formulations and being largely porcine based. The novel microbial lipase NM-BL was safe and effective in this short term trial. The trial provided clinical proof-of-concept for this novel microbial lipase as a treatment for EPI in CF. A larger phase 2 dose ranging trial is warranted. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01710644.
Assuntos
Insuficiência Pancreática Exócrina/tratamento farmacológico , Lipase/uso terapêutico , Adolescente , Criança , Estudos Cross-Over , Fibrose Cística/complicações , Método Duplo-Cego , Insuficiência Pancreática Exócrina/etiologia , Feminino , Humanos , Lipase/efeitos adversos , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To utilize the Cystic Fibrosis Foundation Patient Registry to evaluate whether pancreatic enzyme dose is associated with better nutritional status as measured by average body mass index (BMI) percentile. STUDY DESIGN: A retrospective analysis of the Cystic Fibrosis Foundation Patient Registry from 2005-2008 was performed. The final analysis included 42â561 patient visits from 14â482 patients 2-20 years of age taking pancreatic enzyme replacement therapy from 179 programs. Cystic fibrosis care programs were assigned to quartiles based on adjusted mean patient BMI percentiles. Differences in median lipase dose between programs in the highest and lowest BMI quartiles were examined using a mixed effects model that adjusted for individual patient BMI, age, race, ethnicity, forced expiratory volume in 1 second percent, acid-blocker use, presence of Pseudomonas aeruginosa, nutritional supplement use, growth hormone use, and diagnosis of cystic fibrosis-related diabetes. RESULTS: A significant difference in median enzyme dose existed between the highest and lowest BMI quartiles. Multivariable analysis demonstrated the effect persisted after adjustment for covariates. Highest quartile programs had a median enzyme dose of 1755 lipase units/kg/meal compared with 1628 lipase units/kg/meal for lowest quartile programs. CONCLUSION: Patients attending US cystic fibrosis programs achieving highest nutritional outcomes, measured by mean BMI percentile, have higher enzyme dosing than those attending programs at lower performance levels. Further randomized clinical trials are necessary to determine the role of enzyme dose in improving nutritional outcomes.
Assuntos
Índice de Massa Corporal , Fibrose Cística/complicações , Terapia de Reposição de Enzimas/métodos , Insuficiência Pancreática Exócrina/tratamento farmacológico , Lipase/uso terapêutico , Estado Nutricional , Adolescente , Criança , Pré-Escolar , Esquema de Medicação , Insuficiência Pancreática Exócrina/etiologia , Feminino , Humanos , Masculino , Modelos Estatísticos , Análise Multivariada , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: We studied a novel pancreatic enzyme product, ALTU-135, a proprietary formulation of microbially derived lipase, protease, and amylase, to determine its efficacy and safety in treatment of pancreatic insufficiency (PI) in patients with cystic fibrosis (CF). STUDY DESIGN: Ambulatory subjects with CF-PI (n = 117) had baseline coefficient of fat and nitrogen absorption (CFA and CNA, respectively) determined in an inpatient setting while not receiving pancreatic enzyme replacement therapy. Subjects were then randomized to treatment with ALTU-135 containing 5000 (low), 25,000 (mid), or 100,000 (highest) units of lipase (1:1:0.15 of lipase:protease:amylase) for 28 days. After 14 days, CFA and CNA were re-measured. The primary outcomes were change from baseline in CFA and CNA between treatments. RESULTS: Treatment CFA was significantly greater in the mid and highest dose groups compared with that in the low dose group (P = .0229 and P =.0041, respectively); findings were similar for CNA. Subjects with baseline CFA < or = 40% and > 40% in the 2 higher dose groups had a mean increase of 31 and 8 percentage points in CFA, respectively (P < .0001). CONCLUSION: ALTU-135 was efficacious during the 1-month study period at the dose of 25,000 units of lipase, 25,000 units of protease, and 3750 units of amylase.
Assuntos
Amilases/uso terapêutico , Fibrose Cística/complicações , Insuficiência Pancreática Exócrina/tratamento farmacológico , Insuficiência Pancreática Exócrina/enzimologia , Lipase/uso terapêutico , Peptídeo Hidrolases/uso terapêutico , Adolescente , Adulto , Amilases/administração & dosagem , Amilases/efeitos adversos , Análise de Variância , Glicemia/metabolismo , Criança , Fibrose Cística/enzimologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Insuficiência Pancreática Exócrina/complicações , Gorduras/análise , Gorduras/metabolismo , Fezes/química , Feminino , Seguimentos , Humanos , Absorção Intestinal/efeitos dos fármacos , Lipase/administração & dosagem , Lipase/efeitos adversos , Masculino , Nitrogênio/análise , Nitrogênio/metabolismo , Peptídeo Hidrolases/administração & dosagem , Peptídeo Hidrolases/efeitos adversos , Resultado do TratamentoRESUMO
Uma preparaçäo de pâncreas total suino liofilizado (PTL) foi testada "in vitro" e "in vivo". A atividade lipásica média dos quatro lotes estudados foi 6.180 ñ 1.122 U.I. por grama de produto. Näo havia tripsina livre na preparaçäo. Quinze portadores de insuficiência pancreática exócrina foram estudados em um período de quatro semanas. Os adultos receberam de 35.500 a 35.776 U.I. de lipase, contidas na preparaçäo de PTL, por refeiçäo. Todos experimentaram reduçäo da esteatorréia, ou normalizaçäo, bem como observou-se reduçäo no peso das fezes e aumento do peso corpóreo. Näo há relaçäo obrigatória entre a perda fecal de gordura e o peso das fezes. A esteatorréia decresceu por um mínimo de 14 dias antes de alcançar um nível estável. Esta conclusäo merece ser conhecida: para testar a eficácia de extratos pancreáticos, o tratamento deve ser feito, pelo menos, por duas semanas