This is a clinical trial which will evaluate the efficacy of Liprotamase treatment in cystic fibrosis (CF) patients with exocrine pancreatic insufficiency (PI).

This trial is divided into four distinct periods:

1. Baseline Period during which each patient is taken off pancreatic enzyme medications.
2. An Open-Label Treatment Period during which all patients will receive ALTU-135 (liprotamase).
3. Inpatient, Double Blind Treatment Period during which half of patients will be withdrawn from treatment and will receive Placebo.
4. Second Open-Label Treatment Period during which all patients will resume treatment with ALTU-135 (liprotamase).

Inclusion Criteria:

• Females of childbearing potential must be willing to use birth control

• Diagnosis of CF based upon the following criteria:

  • two clinical features consistent with CF; and

    • either genotype with two identifiable mutations consistent with CF, OR
    • sweat chloride >60 mEq/L by quantitative pilocarpine iontophoresis

• Clinically stable with no evidence of acute upper or lower respiratory tract infection

• PI determined by fecal elastase <100 µg/g stool measured at screening

• Able to take pancreatic enzyme supplementation in the form of capsules

• Able to perform the testing (e.g., stool collections) and inpatient stays required for this study, as judged by the Investigator

• Baseline coefficient of fat absorption (CFA) less than or equal to 80%

Exclusion Criteria:

• CFA >80% at Baseline
• Pregnancy, breastfeeding or of childbearing potential and not willing to use birth control during the study
• History of fibrosing colonopathy
• History of liver transplant, lung transplant or significant surgical resection of the bowel
• Any acute or chronic diarrheal illness unrelated to PI
• Unable to discontinue enteral tube feedings during the study
• Known hypersensitivity to food additives
• Inability to consume the diet required by the study, in the judgment of the Investigator
• Participation in an investigational study of a drug, biologic, or device not currently approved for marketing within 30 days prior to screening
• Abnormal liver function (except for patients with Gilbert Syndrome)
• Signs and/or symptoms of liver cirrhosis, portal hypertension or documented liver disease unrelated to CF
• Distal intestinal obstruction syndrome (DIOS) in the last six months prior to screening
• Unable to discontinue the use of pancreatic enzymes
• Any condition that the Investigator believes would interfere with the intent of this study or would make participation not in the best interest of the patient
• Patient is unlikely to complete the study, as determined by the Investigator