Glycerol Phenylbutyrate Corrector Therapy For CF (Cystic Fibrosis)

• Register: ClinicalTrials.gov
• Last refreshed on: 22 March 2021
• Main ID: NCT02323100
• Date of registration: 18/12/2014
• Prospective Registration: Yes
• Primary sponsor: National Jewish Health
• Public title: Glycerol Phenylbutyrate Corrector Therapy For CF (Cystic Fibrosis) GPBA
• Scientific title: A Double Blind, Placebo Controlled, Dose Escalation Trial of Glycerol Phenylbutyrate Corrector Therapy for Cystic Fibrosis
• Date of first enrolment: December 2, 2018
• Target sample size: 36
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT02323100
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Pamela L Zeitlin, MD, PhD
• Affiliation: National Jewish Health

• Name: Jennifer Brandorff

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or female = 18 years of age.

2. 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.

3. Taking pancreatic enzyme replacement therapy (PERT), or have documented pancreatic
sufficiency.

4. Ability to perform acceptable spirometry.

5. Ability to understand and sign a written informed consent and comply with the
requirements of the study.

6. FEV1 =30% of predicted normal for age, gender, and height (Hankinson standards): pre
or post-bronchodilator at Screening.

7. Oxygen saturation by pulse oximetry =90% breathing either ambient air or regular
oxygen regimen at screening and Day 1.

8. 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.

9. 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

10. Negative pregnancy test for women of child-bearing potential.

11. 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.

Exclusion Criteria:

1. Administration of any investigational drug or device within 30 days of Screening or
within 6 half-lives of the investigational drug (whichever is longer).

2. 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.

3. 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.

4. Pregnant, planned pregnancy or breast feeding at Screening.

5. Clinically significant cardiac, liver or kidney disease.

6. Seizure disorder.

7. Acute upper respiratory infection within 2 weeks or acute pulmonary exacerbation
requiring intravenous antibiotics within 4 weeks of Screening Visit.

8. Sinus surgery within 6 weeks of Screening Visit.

9. Abnormal renal function.

10. Abnormal liver function, defined as =3x upper limit of normal (ULN), of serum
aspartate transaminase (AST) or serum alanine transaminase (ALT), or known cirrhosis.

11. Screening laboratory results which in the judgment of the investigator would interfere
with completion of the study.

12. History of or listed for solid organ or hematological transplantation.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Placebo

Drug: Ravicti high dose

Drug: Ravicti low dose

Primary Outcome(s)

The primary biological endpoint will be the change in average measurement of nasal potential difference between day 7 and baseline. [Time Frame: 7 days]

Secondary Outcome(s)

Change in other NPD measures from baseline and Days 4, 7, and 14 to include baseline PD, change in amiloride, low chloride, and low chloride plus isoproterenol. [Time Frame: 14 days]

Change in average sweat chloride measurement between days 4, 7, 14 and baseline. [Time Frame: 14 days]

Efficacy of PERT on absorption of Ravicti®. [Time Frame: 14 days]

Safety and tolerability. [Time Frame: 14 days]

Secondary ID(s)

GPBA

FD-R-0005380

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University of Alabama at Birmingham

Children's Hospital of Philadelphia

Horizon Pharma Ireland, Ltd., Dublin Ireland

Johns Hopkins University