Chronic Kidney Disease
Conditions
Keywords
Chronic Kidney Disease, Sitaxsentan
Brief summary
This study is being conducted to evaluate sitaxsentan dosing in subjects with chronic kidney disease.
Interventions
DRUGOpen
Sitaxsentan sodium 100 mg orally administered once daily (double blind arm)
DRUGNifedipine
Nifedipine = 30 mg extended release tablets, orally administered once daily (open label arm)
DRUGPlacebo
Placebo for sitaxsentan, orally administered once daily (double blind arm)
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Has stage 1-5 chronic kidney disease (CKD) as defined by the Kidney Disease Outcomes Quality Initiative (K/DOQI) with proteinuria, including any of the following aetiologies: immunoglobulin (IgA) nephropathy, polycystic kidney disease (PCKD), congenital abnormalities, reflux nephropathy, focal segmental glomerulosclerosis, minimal change nephropathy, and membranous nephropathy.
Exclusion criteria
* Required peritoneal dialysis or haemodialysis. * Has kidney disease due to diabetes mellitus, vasculitis, systemic lupus erythematosus, or known renovascular disease; antiglomerular basement membrane disease; or is on immunosuppressive medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean 24-Hour Urine Total Protein Level at Week 6 | Baseline, Week 6 | Mean urine total protein assessment included 24-hour urine collections to assess total protein excretion per 24 hours. Baseline was derived from an average of Week 0 (pre-dose) 24-hour urine collections prior to each treatment period. Week 6 was derived from an average of Week 6 24-hour urine collections for each treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Baseline, Week 3 and 6 | The 24-hour ambulatory BP monitoring was performed by using a BP cuff which was attached to the participant's arm, using the same arm throughout the study, with a small monitor that comfortably sits in the pocket of participant. Mean values over 24-hour measurements at each measurement period were calculated. The change in total 24-hour ambulatory monitoring of systemic arterial BP, SBP and DBP at Week 3 and 6 relative to baseline were reported. Baseline was as an average of the pre-dose measurement for the measure collected at Week 0 of each treatment period. Week 3 and Week 6 was an average of measurement for the measure collected at Week 3 and 6 of each treatment period. |
| Change From Baseline in Carotid-Femoral Pulse Wave Velocity (PWV) at Week 3 and 6 | Baseline, Week 3 and 6 | Carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, is determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. Baseline was defined as the pre-dose measurement for the measure collected at Week 0 of each treatment period. Week 3 and Week 6 was an average of measurement for the measure collected at Week 3 and 6 of each treatment period. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study All participants who were randomized to receive Sitaxsentan 100 mg tablet, Nifedipine ER 30 mg tablet and placebo matched to Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in any intervention period. Each intervention period was separated by a washout period of at least 2 weeks. | 27 |
| Total | 27 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 47.7 years STANDARD_DEVIATION 11.8 |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 27 | 21 / 27 | 18 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 | 0 / 27 |
Outcome results
Primary
Change From Baseline in Mean 24-Hour Urine Total Protein Level at Week 6
Mean urine total protein assessment included 24-hour urine collections to assess total protein excretion per 24 hours. Baseline was derived from an average of Week 0 (pre-dose) 24-hour urine collections prior to each treatment period. Week 6 was derived from an average of Week 6 24-hour urine collections for each treatment period.
Time frame: Baseline, Week 6
Population: FAS included all participants who received at least one dose of study drug and had received at least 1 on-treatment assessment for at least 1 endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan | Change From Baseline in Mean 24-Hour Urine Total Protein Level at Week 6 | Baseline | 2.07 Grams per 24 hours | Standard Deviation 1.77 |
| Sitaxsentan | Change From Baseline in Mean 24-Hour Urine Total Protein Level at Week 6 | Change at week 6 | -0.62 Grams per 24 hours | Standard Deviation 0.56 |
| Placebo | Change From Baseline in Mean 24-Hour Urine Total Protein Level at Week 6 | Change at week 6 | -0.06 Grams per 24 hours | Standard Deviation 0.89 |
| Placebo | Change From Baseline in Mean 24-Hour Urine Total Protein Level at Week 6 | Baseline | 2.07 Grams per 24 hours | Standard Deviation 1.96 |
| Nifedipine | Change From Baseline in Mean 24-Hour Urine Total Protein Level at Week 6 | Change at week 6 | 0.01 Grams per 24 hours | Standard Deviation 0.77 |
| Nifedipine | Change From Baseline in Mean 24-Hour Urine Total Protein Level at Week 6 | Baseline | 1.95 Grams per 24 hours | Standard Deviation 1.58 |
p-value: 0.00495% CI: [-0.94, -0.19]ANCOVA
p-value: 0.001895% CI: [-0.99, -0.24]ANCOVA
p-value: 0.794595% CI: [-0.33, 0.43]ANCOVA
Secondary
Change From Baseline in Carotid-Femoral Pulse Wave Velocity (PWV) at Week 3 and 6
Carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, is determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. Baseline was defined as the pre-dose measurement for the measure collected at Week 0 of each treatment period. Week 3 and Week 6 was an average of measurement for the measure collected at Week 3 and 6 of each treatment period.
Time frame: Baseline, Week 3 and 6
Population: FAS included all participants who received at least one dose of study drug and had received at least 1 on-treatment assessment for at least 1 endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan | Change From Baseline in Carotid-Femoral Pulse Wave Velocity (PWV) at Week 3 and 6 | Change at Week 3 | -0.19 Meter per second | Standard Deviation 0.95 |
| Sitaxsentan | Change From Baseline in Carotid-Femoral Pulse Wave Velocity (PWV) at Week 3 and 6 | Baseline | 7.97 Meter per second | Standard Deviation 1.58 |
| Sitaxsentan | Change From Baseline in Carotid-Femoral Pulse Wave Velocity (PWV) at Week 3 and 6 | Change at Week 6 | -0.41 Meter per second | Standard Deviation 0.82 |
| Placebo | Change From Baseline in Carotid-Femoral Pulse Wave Velocity (PWV) at Week 3 and 6 | Change at Week 3 | -0.21 Meter per second | Standard Deviation 0.69 |
| Placebo | Change From Baseline in Carotid-Femoral Pulse Wave Velocity (PWV) at Week 3 and 6 | Baseline | 7.74 Meter per second | Standard Deviation 1.58 |
| Placebo | Change From Baseline in Carotid-Femoral Pulse Wave Velocity (PWV) at Week 3 and 6 | Change at Week 6 | 0.29 Meter per second | Standard Deviation 1.08 |
| Nifedipine | Change From Baseline in Carotid-Femoral Pulse Wave Velocity (PWV) at Week 3 and 6 | Baseline | 7.94 Meter per second | Standard Deviation 1.74 |
| Nifedipine | Change From Baseline in Carotid-Femoral Pulse Wave Velocity (PWV) at Week 3 and 6 | Change at Week 6 | -0.38 Meter per second | Standard Deviation 0.86 |
| Nifedipine | Change From Baseline in Carotid-Femoral Pulse Wave Velocity (PWV) at Week 3 and 6 | Change at Week 3 | -0.21 Meter per second | Standard Deviation 0.92 |
Comparison: Week 3p-value: 0.882395% CI: [-0.39, 0.45]ANCOVA
Comparison: Week 3p-value: 0.945795% CI: [-0.41, 0.43]ANCOVA
Comparison: Week 3p-value: 0.935895% CI: [-0.4, 0.44]ANCOVA
Comparison: Week 6p-value: 0.002295% CI: [-1.03, -0.25]ANCOVA
Comparison: Week 6p-value: 0.895695% CI: [-0.41, 0.36]ANCOVA
Comparison: Week 6p-value: 0.00395% CI: [-1, -0.23]ANCOVA
Secondary
Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6
The 24-hour ambulatory BP monitoring was performed by using a BP cuff which was attached to the participant's arm, using the same arm throughout the study, with a small monitor that comfortably sits in the pocket of participant. Mean values over 24-hour measurements at each measurement period were calculated. The change in total 24-hour ambulatory monitoring of systemic arterial BP, SBP and DBP at Week 3 and 6 relative to baseline were reported. Baseline was as an average of the pre-dose measurement for the measure collected at Week 0 of each treatment period. Week 3 and Week 6 was an average of measurement for the measure collected at Week 3 and 6 of each treatment period.
Time frame: Baseline, Week 3 and 6
Population: FAS included all participants who received at least one dose of study drug and had received at least 1 on-treatment assessment for at least 1 endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial DBP: Baseline | 77.56 Millimeter of Mercury (mmHg) | Standard Deviation 6.67 |
| Sitaxsentan | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial SBP :Baseline | 124.03 Millimeter of Mercury (mmHg) | Standard Deviation 11.44 |
| Sitaxsentan | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial BP: Change at Week 3 | -4.59 Millimeter of Mercury (mmHg) | Standard Deviation 5.02 |
| Sitaxsentan | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial SBP: Change at Week 6 | -3.99 Millimeter of Mercury (mmHg) | Standard Deviation 7.82 |
| Sitaxsentan | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial SBP: Change at Week 3 | -4.88 Millimeter of Mercury (mmHg) | Standard Deviation 7.34 |
| Sitaxsentan | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial BP: Baseline | 92.94 Millimeter of Mercury (mmHg) | Standard Deviation 7.39 |
| Sitaxsentan | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial DBP: Change at Week 3 | -4.85 Millimeter of Mercury (mmHg) | Standard Deviation 4.51 |
| Sitaxsentan | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial BP: Change at Week 6 | -3.74 Millimeter of Mercury (mmHg) | Standard Deviation 5.62 |
| Sitaxsentan | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial DBP: Change at Week 6 | -3.60 Millimeter of Mercury (mmHg) | Standard Deviation 5.02 |
| Placebo | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial DBP: Baseline | 77.58 Millimeter of Mercury (mmHg) | Standard Deviation 8.05 |
| Placebo | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial BP: Baseline | 92.98 Millimeter of Mercury (mmHg) | Standard Deviation 9.33 |
| Placebo | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial BP: Change at Week 3 | -1.20 Millimeter of Mercury (mmHg) | Standard Deviation 4.7 |
| Placebo | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial BP: Change at Week 6 | -0.35 Millimeter of Mercury (mmHg) | Standard Deviation 5.38 |
| Placebo | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial SBP :Baseline | 125.17 Millimeter of Mercury (mmHg) | Standard Deviation 13.95 |
| Placebo | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial SBP: Change at Week 3 | -2.81 Millimeter of Mercury (mmHg) | Standard Deviation 7.21 |
| Placebo | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial SBP: Change at Week 6 | -1.57 Millimeter of Mercury (mmHg) | Standard Deviation 7.22 |
| Placebo | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial DBP: Change at Week 3 | -0.86 Millimeter of Mercury (mmHg) | Standard Deviation 3.98 |
| Placebo | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial DBP: Change at Week 6 | -0.41 Millimeter of Mercury (mmHg) | Standard Deviation 5.03 |
| Nifedipine | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial SBP: Change at Week 6 | -4.47 Millimeter of Mercury (mmHg) | Standard Deviation 7.97 |
| Nifedipine | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial BP: Change at Week 6 | -3.54 Millimeter of Mercury (mmHg) | Standard Deviation 5.49 |
| Nifedipine | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial DBP: Baseline | 78.27 Millimeter of Mercury (mmHg) | Standard Deviation 7.74 |
| Nifedipine | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial BP: Change at Week 3 | -2.95 Millimeter of Mercury (mmHg) | Standard Deviation 5.9 |
| Nifedipine | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial DBP: Change at Week 6 | -2.86 Millimeter of Mercury (mmHg) | Standard Deviation 4.92 |
| Nifedipine | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial DBP: Change at Week 3 | -2.09 Millimeter of Mercury (mmHg) | Standard Deviation 5.59 |
| Nifedipine | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial SBP: Change at Week 3 | -4.20 Millimeter of Mercury (mmHg) | Standard Deviation 7.67 |
| Nifedipine | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial SBP :Baseline | 125.12 Millimeter of Mercury (mmHg) | Standard Deviation 12.33 |
| Nifedipine | Change From Baseline in Mean Systemic Arterial Blood Pressure (BP), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 3 and 6 | Mean Systemic Arterial BP: Baseline | 93.78 Millimeter of Mercury (mmHg) | Standard Deviation 8.35 |
Comparison: Mean Systemic Arterial BP: Week 3p-value: 0.008795% CI: [-6.08, -0.91]ANCOVA
Comparison: Mean Systemic Arterial BP: Week 3p-value: 0.142495% CI: [-4.5, 0.66]ANCOVA
Comparison: Mean Systemic Arterial BP: Week 3p-value: 0.227795% CI: [-4.15, 1]ANCOVA
Comparison: Systolic Blood Pressure: Week 3p-value: 0.159995% CI: [-6.16, 1.03]ANCOVA
Comparison: Systolic Blood Pressure: Week 3p-value: 0.554595% CI: [-4.66, 2.52]ANCOVA
Comparison: Systolic Blood Pressure: Week 3p-value: 0.409595% CI: [-5.08, 2.09]ANCOVA
Comparison: Diastolic Blood Pressure: Week 3p-value: 0.001295% CI: [-6.49, -1.67]ANCOVA
Comparison: Diastolic Blood Pressure: Week 3p-value: 0.015995% CI: [-5.38, -0.57]ANCOVA
Comparison: Diastolic Blood Pressure: Week 3p-value: 0.362795% CI: [-3.51, 1.3]ANCOVA
Comparison: Mean Systemic Arterial BP: Week 6p-value: 0.005795% CI: [-5.69, -1.03]ANCOVA
Comparison: Mean Systemic Arterial BP: Week 6p-value: 0.650395% CI: [-2.86, 1.8]ANCOVA
Comparison: Mean Systemic Arterial BP: Week 6p-value: 0.018395% CI: [-5.16, -0.5]ANCOVA
Comparison: Systolic Blood Pressure (SBP): Week 6p-value: 0.072695% CI: [-5.89, 0.27]ANCOVA
Comparison: Systolic Blood Pressure (SBP): Week 6p-value: 0.966195% CI: [-3.01, 3.14]ANCOVA
Comparison: Systolic Blood Pressure (SBP): Week 6p-value: 0.065695% CI: [-5.94, 0.19]ANCOVA
Comparison: Diastolic Blood Pressure (DBP): Week 6p-value: 0.006895% CI: [-5.39, -0.92]ANCOVA
Comparison: Diastolic Blood Pressure (DBP): Week 6p-value: 0.37695% CI: [-3.22, 1.24]ANCOVA
Comparison: Diastolic Blood Pressure (DBP): Week 6p-value: 0.057295% CI: [-4.4, 0.07]ANCOVA