Trial Outcomes & Findings for Effects of Sildenafil on CFTR-dependent Ion Transport Activity (NCT NCT01132482)
NCT ID: NCT01132482
Last Updated: 2019-03-19
Results Overview
Amount of sodium transported across the nasal epithelium
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
19 participants
Primary outcome timeframe
Baseline and day 28
Results posted on
2019-03-19
Participant Flow
Participant milestones
| Measure |
Sildenafil
Subjects will receive escalating doses of sildenafil
Sildenafil: During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
|
Placebo
During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.
Placebo: Patients receiving placebo will have sham dose escalation to maintain blinding.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
6
|
|
Overall Study
COMPLETED
|
12
|
6
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Sildenafil
Subjects will receive escalating doses of sildenafil
Sildenafil: During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
|
Placebo
During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.
Placebo: Patients receiving placebo will have sham dose escalation to maintain blinding.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
Effects of Sildenafil on CFTR-dependent Ion Transport Activity
Baseline characteristics by cohort
| Measure |
Sildenafil
n=12 Participants
Subjects will receive escalating doses of sildenafil
Sildenafil: During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
|
Placebo
n=6 Participants
During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.
Placebo: Patients receiving placebo will have sham dose escalation to maintain blinding.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
27.1 years
n=5 Participants
|
28 years
n=7 Participants
|
27.6 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
6 participants
n=7 Participants
|
18 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and day 28Population: Patients with CF homozygous for the F508del genotype with mild, stable lung disease
Amount of sodium transported across the nasal epithelium
Outcome measures
| Measure |
Sildenafil
n=12 Participants
Subjects will receive escalating doses of sildenafil
Sildenafil: During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
|
Placebo
n=6 Participants
During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.
Placebo: Patients receiving placebo will have sham dose escalation to maintain blinding.
|
|---|---|---|
|
Change in Sodium Conductance by Nasal Potential Difference (NPD)
|
-0.70 mV
Standard Deviation 9.18
|
1.81 mV
Standard Deviation 7.99
|
SECONDARY outcome
Timeframe: Baseline and day 28Population: Patients with CF homozygous for the F508del mutation with stable, mild lung disease
Amount of chloride transport across the nasal epithelium
Outcome measures
| Measure |
Sildenafil
n=12 Participants
Subjects will receive escalating doses of sildenafil
Sildenafil: During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
|
Placebo
n=6 Participants
During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.
Placebo: Patients receiving placebo will have sham dose escalation to maintain blinding.
|
|---|---|---|
|
Change in Chloride Conductance by NPD
|
2.53 mV
Standard Deviation 7.58
|
-0.28 mV
Standard Deviation 8.93
|
SECONDARY outcome
Timeframe: Baseline and day 28Population: Patients with CF homozygous for the F508del mutation with mild, stable lung disease. One patient in the sildenafil group had insufficient sweat for analysis.
Amount of chloride transport across the skin
Outcome measures
| Measure |
Sildenafil
n=11 Participants
Subjects will receive escalating doses of sildenafil
Sildenafil: During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
|
Placebo
n=6 Participants
During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.
Placebo: Patients receiving placebo will have sham dose escalation to maintain blinding.
|
|---|---|---|
|
Change in Sweat Chloride Concentration by Pilocarpine Iontophoresis
|
6.13 mmol/L
Standard Deviation 14.4
|
-0.42 mmol/L
Standard Deviation 11.91
|
SECONDARY outcome
Timeframe: Baseline and day 28Population: Patients with CF homozygous for the F508del mutation with mild, stable lung disease
ppFEV1
Outcome measures
| Measure |
Sildenafil
n=12 Participants
Subjects will receive escalating doses of sildenafil
Sildenafil: During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
|
Placebo
n=6 Participants
During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.
Placebo: Patients receiving placebo will have sham dose escalation to maintain blinding.
|
|---|---|---|
|
Change in Pulmonary Function by Spirometry
|
-0.92 % predicted
Standard Deviation 6.53
|
-1.00 % predicted
Standard Deviation 3.69
|
SECONDARY outcome
Timeframe: Baseline and day 28Population: Patients with CF homozygous for the F508del mutation with mild, stable lung disease
Trough sildenafil levels
Outcome measures
| Measure |
Sildenafil
n=12 Participants
Subjects will receive escalating doses of sildenafil
Sildenafil: During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
|
Placebo
n=6 Participants
During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.
Placebo: Patients receiving placebo will have sham dose escalation to maintain blinding.
|
|---|---|---|
|
Change in Serum Sildenafil Pharmacokinetics
|
0 ug/mL
Standard Deviation 0
|
0 ug/mL
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Baseline and day 28Population: Patients with CF homozygous for the F508del mutation with mild, stable lung disease
Respiratory domain of the CFQ-R; The range of scores is 0-100, with higher scores indicating better health.
Outcome measures
| Measure |
Sildenafil
n=12 Participants
Subjects will receive escalating doses of sildenafil
Sildenafil: During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
|
Placebo
n=6 Participants
During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.
Placebo: Patients receiving placebo will have sham dose escalation to maintain blinding.
|
|---|---|---|
|
Change in CF Heath Related Quality of Life Questionnaire (CFQ-R)
|
-1.87 units on a scale
Standard Deviation 14.26
|
0.00 units on a scale
Standard Deviation 14.04
|
SECONDARY outcome
Timeframe: Baseline and day 28Population: Patients with CF homozygous for the F508del mutation with mild, stable lung disease who had valid data for measure
The lung clearance index (LCI) measures how long it takes for an inert gas (e.g. nitrogen) to be washed out of the lungs during relaxed tidal breathing. A higher value of the LCI indicates worse disease. LCI is calculated as the number of functional residual capacity (FRC) turnovers required to reduce the end-tidal concentration of nitrogen to 1/40th of the starting concentration and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured FRC.
Outcome measures
| Measure |
Sildenafil
n=9 Participants
Subjects will receive escalating doses of sildenafil
Sildenafil: During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
|
Placebo
n=5 Participants
During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.
Placebo: Patients receiving placebo will have sham dose escalation to maintain blinding.
|
|---|---|---|
|
Change in Lung Clearance Index
|
-0.33 LCI
Standard Deviation 1.77
|
-1.14 LCI
Standard Deviation 2.94
|
Adverse Events
Sildenafil
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sildenafil
n=12 participants at risk
Subjects will receive escalating doses of sildenafil
Sildenafil: During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
|
Placebo
n=6 participants at risk
During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.
Placebo: Patients receiving placebo will have sham dose escalation to maintain blinding.
|
|---|---|---|
|
Gastrointestinal disorders
DIOS
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary exacerbation
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
Other adverse events
| Measure |
Sildenafil
n=12 participants at risk
Subjects will receive escalating doses of sildenafil
Sildenafil: During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
|
Placebo
n=6 participants at risk
During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.
Placebo: Patients receiving placebo will have sham dose escalation to maintain blinding.
|
|---|---|---|
|
General disorders
Pain, throat
|
16.7%
2/12 • Number of events 2 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
General disorders
Pain, head
|
41.7%
5/12 • Number of events 7 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
General disorders
Rhinorrhea
|
16.7%
2/12 • Number of events 2 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.7%
2/12 • Number of events 2 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Skin and subcutaneous tissue disorders
Flushing
|
0.00%
0/12 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Respiratory, thoracic and mediastinal disorders
Pain, chest
|
16.7%
2/12 • Number of events 2 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Gastrointestinal disorders
Heartburn
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
16.7%
2/12 • Number of events 2 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Gastrointestinal disorders
Elevated ALT
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Gastrointestinal disorders
Elevated AST
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Gastrointestinal disorders
Distension/bloating, abdominal
|
0.00%
0/12 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Respiratory, thoracic and mediastinal disorders
upper respiratory tract infection
|
0.00%
0/12 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
General disorders
Fatigue
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary exacerbation
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
|
Respiratory, thoracic and mediastinal disorders
Increased sputum clearance
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
0.00%
0/6 • Adverse events were collected from the time of screening to 1 week following the last dose of study drug (approximately 2 months).
|
Additional Information
Jennifer Taylor-Cousar, Principal Investigator
National Jewish Health
Phone: 3032702764
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place