Effects of Sildenafil on CFTR-dependent Ion Transport Activity

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01132482
• Date of registration: 16/04/2010
• Prospective Registration: Yes
• Primary sponsor: National Jewish Health
• Public title: Effects of Sildenafil on CFTR-dependent Ion Transport Activity
• Scientific title: Phase II Study of the Effects of Sildenafil on CFTR-dependent Ion Transport Activity
• Date of first enrolment: October 2015
• Target sample size: 19
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01132482
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Jennifer L Taylor-Cousar, MD
• Affiliation: National Jewish Health

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Confirmed diagnosis of CF based on the following criteria: Positive sweat chloride
=60mEq/liter (by pilocarpine iontophoresis) and genotype with two F508del CFTR
mutations, and accompanied by one or more clinical features consistent with the CF
phenotype

2. Male or female subjects = 18 years of age

3. FEV1 = 50% predicted (Hankinson)

4. Clinically stable without evidence of acute upper or lower respiratory tract infection
or current pulmonary exacerbation within the 14 days prior to the screening visit

5. Ability to reproducibly perform spirometry (according to ATS criteria)

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

7. Willing and able to perform nasal potential difference testing

8. No changes in use of nasal medications within 2 weeks of screening visit

9. If on Orkambi, has been on stable Orkambi dose for at least 4 weeks at day 1.

Exclusion Criteria:

1. History of hypersensitivity to sildenafil

2. Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0)

3. Breastfeeding, pregnant, or verbal expression of unwillingness to practice an
acceptable birth control method (abstinence, hormonal or barrier methods, partner
sterilization or intrauterine device) during participation in the study

4. History of significant hepatic (SGOT or SGPT > 3 times the upper limit of normal at
screening, documented biliary cirrhosis, or portal hypertension), cardiovascular
(history of aortic stenosis, coronary artery disease, pulmonary hypertension with
right ventricular systolic pressure >55 mmHg or life-threatening arrhythmia),
neurological (history of stroke), hematologic (history of bleeding diathesis),
ophthalmologic (history of retinal impairment or non-arteritic ischemic optic
neuritis) or renal impairment (creatinine >1.8 mg/dL.)

5. Inability to swallow pills

6. Previous lung transplantation

7. Use of concomitant nitrates, a-blocker, or Ca channel blocker

8. Use of concomitant medications known to be potent inhibitors of CYP3A4 (e.g.
ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin,
verapamil)

9. Presence of a condition or abnormality that in the opinion of the investigator would
compromise the safety of the subject or the quality of the data

10. Weight less than 40 kg

11. History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years
of screening

12. History of nasal disease or nasal surgery that would, in the opinion of the
investigator, impede accurate measurements of NPD

13. Use of anticoagulant medication (e.g. heparin, coumadin)

14. Resting room air oxygen saturation <93%

15. Use of nighttime oxygen

15) History of migraine headaches 16) Baseline BP of < 90/50 mm Hg



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

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Sildenafil

Drug: Placebo

Primary Outcome(s)

Change in Sodium Conductance by Nasal Potential Difference (NPD) [Time Frame: Baseline and day 28]

Secondary Outcome(s)

Change in CF Heath Related Quality of Life Questionnaire (CFQ-R) [Time Frame: Baseline and day 28]

Change in Lung Clearance Index [Time Frame: Baseline and day 28]

Change in Pulmonary Function by Spirometry [Time Frame: Baseline and day 28]

Change in Serum Sildenafil Pharmacokinetics [Time Frame: Baseline and day 28]

Change in Sweat Chloride Concentration by Pilocarpine Iontophoresis [Time Frame: Baseline and day 28]

Change in Chloride Conductance by NPD [Time Frame: Baseline and day 28]

Secondary ID(s)

Sildenafil CFTR

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 26/02/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01132482