Trial Outcomes & Findings for Effects Of Sitaxsentan On Proteinuria, 24-Hour Blood Pressure, And Arterial Stiffness In Chronic Kidney Disease Subjects (NCT NCT00810732)
NCT ID: NCT00810732
Last Updated: 2023-07-06
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
27 participants
Primary outcome timeframe
Baseline, Week 6
Results posted on
2023-07-06
Participant Flow
Participant milestones
| Measure |
Placebo Then Sitaxsentan Then Nifedipine
Participants received placebo matched to Sitaxsentan 100 milligram (mg) tablet orally, once daily for 6 weeks in first intervention period, then Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in second intervention period, followed by Nifedipine extended release (ER) 30 mg tablet orally, once daily for 6 weeks in third intervention period. Each intervention period was separated by a washout period of at least 2 weeks.
|
Sitaxsentan Then Nifedipine Then Placebo
Participants received Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in first intervention period, then nifedipine ER 30 mg tablet orally, once daily for 6 weeks in second intervention period, followed by placebo matched Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in third intervention period. Each intervention period was separated by a washout period of at least 2 weeks.
|
Nifedipine Then Sitaxsentan Then Placebo
Participants received Nifedipine ER 30 mg tablet orally, once daily for 6 weeks in first intervention period, then Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in second intervention period, followed by placebo matched to Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in third intervention period. Each intervention period was separated by a washout period of at least 2 weeks.
|
Nifedipine Then Placebo Then Sitaxsentan
Participants received Nifedipine ER 30 mg tablet orally, once daily for 6 weeks in first intervention period, then placebo matched to Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in second intervention period, followed by Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in third intervention period. Each intervention period was separated by a washout period of at least 2 weeks.
|
Placebo Then Nifedipine Then Sitaxsentan
Participants received placebo matched to Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in first intervention period, then Nifedipine ER 30 mg tablet orally, once daily for 6 weeks in second intervention period, followed by Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in third intervention period. Each intervention period was separated by a washout period of at least 2 weeks.
|
Sitaxsentan Then Placebo Then Nifedipine
Participants received Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in first intervention period, then placebo matched to Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in second intervention period, followed by Nifedipine ER 30 mg tablet orally, once daily for 6 weeks in third intervention period. Each intervention period was separated by a washout period of at least 2 weeks.
|
|---|---|---|---|---|---|---|
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First Intervention Period (6 Weeks)
STARTED
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5
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4
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4
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5
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5
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4
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First Intervention Period (6 Weeks)
COMPLETED
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5
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4
|
4
|
5
|
5
|
4
|
|
First Intervention Period (6 Weeks)
NOT COMPLETED
|
0
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0
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0
|
0
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0
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0
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First Washout Period (at Least 2 Weeks)
STARTED
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5
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4
|
4
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5
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5
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4
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First Washout Period (at Least 2 Weeks)
COMPLETED
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5
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4
|
4
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5
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5
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4
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|
First Washout Period (at Least 2 Weeks)
NOT COMPLETED
|
0
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0
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0
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0
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0
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0
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Second Intervention Period (6 Weeks)
STARTED
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5
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4
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4
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5
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5
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4
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Second Intervention Period (6 Weeks)
COMPLETED
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5
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4
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4
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5
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5
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4
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Second Intervention Period (6 Weeks)
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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Second Washout Period (at Least 2 Weeks)
STARTED
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5
|
4
|
4
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5
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5
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4
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Second Washout Period (at Least 2 Weeks)
COMPLETED
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5
|
4
|
4
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5
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5
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4
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|
Second Washout Period (at Least 2 Weeks)
NOT COMPLETED
|
0
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0
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0
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0
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0
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0
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Third Intervention Period (6 Weeks)
STARTED
|
5
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4
|
4
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5
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5
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4
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Third Intervention Period (6 Weeks)
COMPLETED
|
5
|
4
|
4
|
5
|
5
|
4
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|
Third Intervention Period (6 Weeks)
NOT COMPLETED
|
0
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0
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0
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0
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0
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effects Of Sitaxsentan On Proteinuria, 24-Hour Blood Pressure, And Arterial Stiffness In Chronic Kidney Disease Subjects
Baseline characteristics by cohort
| Measure |
Overall Study
n=27 Participants
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.
|
|---|---|
|
Age, Continuous
|
47.7 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 6Population: 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.
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.
Outcome measures
| Measure |
Sitaxsentan
n=27 Participants
Participants received Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in either first, second or third intervention period.
|
Placebo
n=27 Participants
Participants administered placebo matched to 100 mg tablets orally, once daily for 6 weeks in either first, second or third intervention period.
|
Nifedipine
n=27 Participants
Participants were administered Nifedipine 30 mg ER tablet orally, once daily for 6 weeks in either first, second or third intervention period.
|
|---|---|---|---|
|
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
|
2.07 Grams per 24 hours
Standard Deviation 1.96
|
1.95 Grams per 24 hours
Standard Deviation 1.58
|
|
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
|
-0.06 Grams per 24 hours
Standard Deviation 0.89
|
0.01 Grams per 24 hours
Standard Deviation 0.77
|
SECONDARY outcome
Timeframe: Baseline, Week 3 and 6Population: 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.
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.
Outcome measures
| Measure |
Sitaxsentan
n=27 Participants
Participants received Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in either first, second or third intervention period.
|
Placebo
n=27 Participants
Participants administered placebo matched to 100 mg tablets orally, once daily for 6 weeks in either first, second or third intervention period.
|
Nifedipine
n=27 Participants
Participants were administered Nifedipine 30 mg ER tablet orally, once daily for 6 weeks in either first, second or third intervention period.
|
|---|---|---|---|
|
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
|
92.98 Millimeter of Mercury (mmHg)
Standard Deviation 9.33
|
93.78 Millimeter of Mercury (mmHg)
Standard Deviation 8.35
|
|
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
|
-1.57 Millimeter of Mercury (mmHg)
Standard Deviation 7.22
|
-4.47 Millimeter of Mercury (mmHg)
Standard Deviation 7.97
|
|
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
|
-1.20 Millimeter of Mercury (mmHg)
Standard Deviation 4.70
|
-2.95 Millimeter of Mercury (mmHg)
Standard Deviation 5.90
|
|
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
|
-0.35 Millimeter of Mercury (mmHg)
Standard Deviation 5.38
|
-3.54 Millimeter of Mercury (mmHg)
Standard Deviation 5.49
|
|
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
|
125.17 Millimeter of Mercury (mmHg)
Standard Deviation 13.95
|
125.12 Millimeter of Mercury (mmHg)
Standard Deviation 12.33
|
|
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
|
-2.81 Millimeter of Mercury (mmHg)
Standard Deviation 7.21
|
-4.20 Millimeter of Mercury (mmHg)
Standard Deviation 7.67
|
|
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
|
77.58 Millimeter of Mercury (mmHg)
Standard Deviation 8.05
|
78.27 Millimeter of Mercury (mmHg)
Standard Deviation 7.74
|
|
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
|
-0.86 Millimeter of Mercury (mmHg)
Standard Deviation 3.98
|
-2.09 Millimeter of Mercury (mmHg)
Standard Deviation 5.59
|
|
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
|
-0.41 Millimeter of Mercury (mmHg)
Standard Deviation 5.03
|
-2.86 Millimeter of Mercury (mmHg)
Standard Deviation 4.92
|
SECONDARY outcome
Timeframe: Baseline, Week 3 and 6Population: 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.
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.
Outcome measures
| Measure |
Sitaxsentan
n=27 Participants
Participants received Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in either first, second or third intervention period.
|
Placebo
n=27 Participants
Participants administered placebo matched to 100 mg tablets orally, once daily for 6 weeks in either first, second or third intervention period.
|
Nifedipine
n=27 Participants
Participants were administered Nifedipine 30 mg ER tablet orally, once daily for 6 weeks in either first, second or third intervention period.
|
|---|---|---|---|
|
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
|
7.74 Meter per second
Standard Deviation 1.58
|
7.94 Meter per second
Standard Deviation 1.74
|
|
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
|
-0.21 Meter per second
Standard Deviation 0.69
|
-0.21 Meter per second
Standard Deviation 0.92
|
|
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
|
0.29 Meter per second
Standard Deviation 1.08
|
-0.38 Meter per second
Standard Deviation 0.86
|
Adverse Events
Sitaxsentan
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 21 other events
Deaths: 0 deaths
Nifedipine
Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sitaxsentan
n=27 participants at risk
Participants received Sitaxsentan 100 mg tablet orally, once daily for 6 weeks in either first, second or third intervention period.
|
Placebo
n=27 participants at risk
Participants administered placebo matched to 100 mg tablets orally, once daily for 6 weeks in either first, second or third intervention period.
|
Nifedipine
n=27 participants at risk
Participants were administered Nifedipine 30 mg ER tablet orally, once daily for 6 weeks in either first, second or third intervention period.
|
|---|---|---|---|
|
Nervous system disorders
Dizziness
|
3.7%
1/27
|
7.4%
2/27
|
3.7%
1/27
|
|
Nervous system disorders
Headache
|
7.4%
2/27
|
37.0%
10/27
|
37.0%
10/27
|
|
Nervous system disorders
Migraine
|
3.7%
1/27
|
7.4%
2/27
|
0.00%
0/27
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.7%
1/27
|
7.4%
2/27
|
7.4%
2/27
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/27
|
3.7%
1/27
|
3.7%
1/27
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
3.7%
1/27
|
0.00%
0/27
|
0.00%
0/27
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Vascular disorders
Flushing
|
3.7%
1/27
|
0.00%
0/27
|
7.4%
2/27
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/27
|
3.7%
1/27
|
0.00%
0/27
|
|
Eye disorders
Conjunctivitis
|
3.7%
1/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Eye disorders
Eye disorder
|
0.00%
0/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Eye disorders
Iritis
|
0.00%
0/27
|
3.7%
1/27
|
0.00%
0/27
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.7%
1/27
|
3.7%
1/27
|
0.00%
0/27
|
|
Gastrointestinal disorders
Change of bowel habit
|
0.00%
0/27
|
3.7%
1/27
|
0.00%
0/27
|
|
Gastrointestinal disorders
Diarrhoea
|
3.7%
1/27
|
7.4%
2/27
|
0.00%
0/27
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/27
|
3.7%
1/27
|
0.00%
0/27
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/27
|
7.4%
2/27
|
0.00%
0/27
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/27
|
7.4%
2/27
|
3.7%
1/27
|
|
General disorders
Fatigue
|
3.7%
1/27
|
3.7%
1/27
|
0.00%
0/27
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/27
|
3.7%
1/27
|
0.00%
0/27
|
|
Infections and infestations
Balanitis candida
|
0.00%
0/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Infections and infestations
Candidiasis
|
0.00%
0/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/27
|
3.7%
1/27
|
0.00%
0/27
|
|
Infections and infestations
Infusion site infection
|
0.00%
0/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Infections and infestations
Upper respiratory tract infection
|
7.4%
2/27
|
3.7%
1/27
|
11.1%
3/27
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/27
|
3.7%
1/27
|
3.7%
1/27
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Investigations
Blood creatinine increased
|
3.7%
1/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Metabolism and nutrition disorders
Gout
|
3.7%
1/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/27
|
0.00%
0/27
|
3.7%
1/27
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/27
|
7.4%
2/27
|
7.4%
2/27
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/27
|
3.7%
1/27
|
0.00%
0/27
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/27
|
3.7%
1/27
|
7.4%
2/27
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER