Glycerol Phenylbutyrate Corrector Therapy For CF (Cystic Fibrosis)

NCT02323100 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: GPBAFD-R-0005380
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

Brief Summary

We propose to test the effectiveness of the combination of CF pancreatic enzyme replacement therapy (PERT) on absorption of Ravicti® and subsequent restoration of nasal epithelial cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride transport during the nasal potential difference (NPD) test. Funding source FDA Office of Orphan Products Development.

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis; corrector; glycerol phenylbutyrate; nasal potential difference

Outcome Measures

Primary Outcomes (1)

• Change in Chloride and Sodium Transport in Nasal Epithelium

  Change in average measurement of nasal potential difference in millivolts (mV) between baseline (Visit 0) and Day 4 (Visit 2) or Day 7 (Visit 3). Note: the outcome is assessed as change in mV at each visit, and then comparisons between visits are made.

  7 days

Secondary Outcomes (18)

• Change in Average Sweat Chloride

  7 days of treatment as measured on Day 1 (Visit 1) and Day 7 (Visit 3)

• Change in Baseline Nasal Potential Difference (NPD)

  4 days and 7 days of study drug treatment

• Change in Nasal Potential Difference With Perfusion of a Solution Containing Amiloride

  4 and 7 days

• Change in Nasal Potential Difference During Perfusion With a Low Chloride Solution Containing Amiloride

  4 and 7 days

• Change in Nasal Potential Difference With a Low Chloride Solution Containing Amiloride Plus the Change With a Low Chloride Solution Containing Amiloride and Isoproterenol

  4 and 7 days

Other Outcomes (1)

• Pharmacokinetics (PK) Studies

  4 days

Study Arms (2)

Ravicti low dose

ACTIVE COMPARATOR

Low dose Ravicti® oral liquid at 6ml (6.6 gm) by mouth or gastrostomy tube at 8 am, 5.5 ml (6.05gm) at 4pm and midnight for 7 days.

Drug: Ravicti low dose

Placebo

PLACEBO COMPARATOR

Matching placebo taken at 8am, 4pm and midnight for 7 days.

Drug: Placebo

Interventions

Ravicti low dose DRUG

8 am, 4pm and midnight

Also known as: Ravicti, glycerol phenylbutyrate

Ravicti low dose

Placebo DRUG

8 am, 4pm and midnight

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 years of age.
• Confirmed diagnosis of CF based on the following criteria:
• any CFTR genotype combination EXCEPT two stop codons, and one or more clinical features consistent with the CF phenotype.
• Taking pancreatic enzyme replacement therapy (PERT), or have documented pancreatic sufficiency.
• Ability to perform acceptable spirometry.
• Ability to understand and sign a written informed consent and comply with the requirements of the study.
• FEV1 ≥30% of predicted normal for age, gender, and height (Hankinson standards): pre or post-bronchodilator at Screening.
• Oxygen saturation by pulse oximetry ≥90% breathing either ambient air or regular oxygen regimen at screening and Day 1.
• Hematology and clinical chemistry of blood and urine results with no clinically significant abnormalities that would interfere with the study assessments (as judged by the principal investigator) at screening. If electrolyte abnormality at screening, values must be corrected prior to dosing.
• Subjects on chronic inhaled antibiotic therapy are eligible if they can continue their usual antibiotic regimen, or remain on their off-cycle period, for the duration of study drug exposure
• Negative pregnancy test for women of child-bearing potential.
• If of childbearing potential, agree to use one highly effective method of contraception from the time of consent through the Visit 4 study visit, per section 9.1.13 of the protocol.

You may not qualify if:

• Administration of any investigational drug or device within 30 days of Screening or within 6 half-lives of the investigational drug (whichever is longer).
• History of any illness or condition that in the opinion of the investigator could confound the results of the study or pose additional risk in administering study drug to subjects.
• Any change in chronic therapies for CF lung disease (e.g., Ibuprofen, Pulmozyme®, hypertonic saline, Azithromycin, TOBI®, Cayston®) within 4 weeks of Study Day 1.
• Pregnant, planned pregnancy or breast feeding at Screening.
• Clinically significant cardiac, liver or kidney disease.
• Seizure disorder.
• Acute upper respiratory infection within 2 weeks or acute pulmonary exacerbation requiring intravenous antibiotics within 4 weeks of Screening Visit.
• Sinus surgery within 6 weeks of Screening Visit.
• Abnormal renal function.
• Abnormal liver function, defined as ≥3x upper limit of normal (ULN), of serum aspartate transaminase (AST) or serum alanine transaminase (ALT), or known cirrhosis.
• Screening laboratory results which in the judgment of the investigator would interfere with completion of the study.
• History of or listed for solid organ or hematological transplantation.

Sponsors & Collaborators

• National Jewish Health: lead
• University of Alabama at Birmingham: collaborator
• Children's Hospital of Philadelphia: collaborator
• Johns Hopkins University: collaborator
• Horizon Pharma Ireland, Ltd., Dublin Ireland: collaborator

Study Sites (3)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• Johns Hopkins CF research office

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

glycerol phenylbutyrate

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Pamela L. Zeitlin, Chair, Department of Pediatrics
• Organization: National Jewish Health

zeitlinp@njhealth.org

303-398-1196

Study Officials

• Pamela L Zeitlin, MD, PhD

  National Jewish Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: December 23, 2014
• Study Start: December 2, 2018
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2022
• Last Updated: April 17, 2026
• Results First Posted: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)