A comparison of the efficacy and tolerance of pancrelipase and placebo in the treatment of steatorrhea in cystic fibrosis patients with clinical exocrine pancreatic insufficiency

Stern, Robert C.; Eisenberg, Jay D.; Wagener, J.; Ahrens, Richard C.; Rock, Michael J.; doPico, Guillermo A.; Orenstein, David M.

doi:10.1111/j.1572-0241.2000.02244.x

Cited by 77 publications

(53 citation statements)

References 5 publications

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“…Antispasmodic agents such as hyoscyamine and dicyclomine are often prescribed but have not been established to be beneficial and may lose any possible benefit over time 7. Pancrealipase (PEZ) has been shown to reduce bile acid malabsorption in patients with cystic fibrosis,26–28 chronic pancreatitis,29 fat malabsorption due to HIV30 and improve digestion in normal patients consuming a fatty meal 31. PEZ has recently been reported as being effective for the postprandial IBS-D condition32 and among patients identified with pancreatic insufficiency who also have IBS 33.…”

Section: Introductionmentioning

confidence: 99%

Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea

Money

Walkowiak

Virgilio

et al. 2010

Frontline Gastroenterol

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ObjectiveTo evaluate the efficacy of pancrealipase (PEZ) compared with placebo in the reduction of postprandial irritable bowel syndrome-diarrhoea (IBS-D).DesignAn intention to treat, double blind, randomised, crossover trial comparing PEZ to placebo for reduction of postprandial IBS-D. Patients had to recognise at least two different triggering foods, be willing to consume six baseline ‘trigger meals’ and again blinded with PEZ and placebo. Patients then chose which drug they preferred for another 25 meals.SettingOutpatient internal medicine practice clinic.Patients255 patients were screened; 83 met the criteria, including 5 years of symptoms, recognised ‘food triggers’, no other identifiable cause for the symptoms, either a normal colonoscopy or barium enema while symptomatic and able to discontinue all anticholinergic medications. 69 patients were enrolled, 20 withdrew before randomisation, leaving 49 patients: 14 men, 35 women, mean age 52 years (SD 15.3). Over 60% had experienced symptoms for 11–30 years and 16% for more than 40 years.InterventionsAfter completing six baseline meals, patients were randomised in blocks of four to receive either identical PEZ or a placebo for another six meals, and after a washout period of time received the alternative drug.Main outcome measuresThe primary analysis was number of patients who chose PEZ over placebo for the extended use.ResultsOverall, 30/49 (61%) would have chosen PEZ (p=0.078), with first drug preference for PEZ at 0.002. Among the PEZ subgroup, PEZ use compared with placebo, demonstrated improvement in all symptoms (p≤0.001) for cramping, bloating, borborygami, urge to defecate, global pain and decrease stooling with increase in stool firmness.ConclusionsPEZ was found in a small group of patients to reduce postprandial IBS-D symptoms and deserves further evaluation.

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Section: Introductionmentioning

confidence: 99%

Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea

Money

Walkowiak

Virgilio

et al. 2010

Frontline Gastroenterol

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“…Pancreatic insufficiency—pancreatic enzyme replacement therapy (PERT) containing multiple combinations of proteases, lipases and amylases [27]. …”

Section: Treatmentmentioning

confidence: 99%

Cystic fibrosis: current therapeutic targets and future approaches

2017

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ObjectivesStudy of currently approved drugs and exploration of future clinical development pipeline therapeutics for cystic fibrosis, and possible limitations in their use.MethodsExtensive literature search using individual and a combination of key words related to cystic fibrosis therapeutics.Key findingsCystic fibrosis is an autosomal recessive disorder due to mutations in CFTR gene leading to abnormality of chloride channels in mucus and sweat producing cells. Respiratory system and GIT are primarily involved but eventually multiple organs are affected leading to life threatening complications. Management requires drug therapy, extensive physiotherapy and nutritional support. Previously, the focus was on symptomatic improvement and complication prevention but recently the protein rectifiers are being studied which are claimed to correct underlying structural and functional abnormalities. Some improvement is observed by the corrector drugs. Other promising approaches are gene therapy, targeting of cellular interactomes, and newer drugs for symptomatic improvement.ConclusionsThe treatment has a long way to go as most of the existing therapeutics is for older children. Other limiting factors include mutation class, genetic profile, drug interactions, adverse effects, and cost. Novel approaches like gene transfer/gene editing, disease modeling and search for alternative targets are warranted.

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“…It should be pointed out that here, and throughout the rest of this paper, the percent change indicates an absolute difference rather than a relative one (e.g., a change in CFA from 60 to 70% may be referred to as a 10% increase, but represents a 16.7% relative improvement). Since most of the PERT products studied in patients with CF resulted in a 30% or greater increase in CFA compared with placebo in a substantial number of studies [4–9], this effect size could be the benchmark for short-term efficacy studies; however, PERT products demonstrating a <30% increase in CFA on treatment compared with placebo have also been approved by the FDA [10]. Of note, a systematic review of the literature was unable to find sufficient evidence to establish a dose-response association between PERT products and CFA or growth [11].…”

Section: Efficacy Outcome Measuresmentioning

confidence: 99%

“…Thus, the overall treatment effect and variability assumptions are the same between a parallel reintroduction design and a parallel withdrawal design, but there are fewer courses off enzyme or on placebo in a parallel withdrawal design. Two of the eight clinical trials assessing PERT products cited in this paper utilized the parallel withdrawal design [4,10]. …”

Section: Efficacy Outcome Measuresmentioning

confidence: 99%

“…The most concerning and serious acute gastrointestinal adverse event is intestinal obstruction. Patients with CF may develop distal intestinal obstructive syndrome, which has occurred in published PERT trials, primarily with exposure to placebo [4,5,48]. Placebo exposure has also been associated with an increased incidence of abdominal pain, diarrhea, cramping and flatulence.…”

Section: Efficacy Outcome Measuresmentioning

confidence: 99%

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Study design considerations for evaluating the efficacy and safety of pancreatic enzyme replacement therapy in patients with cystic fibrosis

Konstan

Borowitz

Mayer-Hamblett

et al. 2013

Clinical Investigation

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In 2006, the US FDA issued a ‘Guidance for Industry’ regarding submission of New Drug Applications for pancreatic enzyme replacement therapy (PERT) products. Five oral delayed-release PERT products have been approved by the FDA, and several others are under development and/ or evaluation for New Drug Application submission. We present in this paper recommendations of the Cystic Fibrosis Foundation's Cystic Fibrosis (CF) Therapeutics Development Network and Data Safety Monitoring Board regarding study design considerations for evaluating PERT products in patients with CF. Careful attention to study design and accuracy of the outcome measures has confirmed our understanding of the efficacy and safety of PERT for the treatment of exocrine pancreatic insufficiency of CF.

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A comparison of the efficacy and tolerance of pancrelipase and placebo in the treatment of steatorrhea in cystic fibrosis patients with clinical exocrine pancreatic insufficiency

Abstract: Enteric-coated, delayed-release (Minimicrospheres) pancrelipase capsules are an effective treatment for steatorrhea associated with pancreatic insufficiency in patients with cystic fibrosis.

Cited by 77 publications

References 5 publications

Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea

Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea

Cystic fibrosis: current therapeutic targets and future approaches

Study design considerations for evaluating the efficacy and safety of pancreatic enzyme replacement therapy in patients with cystic fibrosis

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