Trial Outcomes & Findings for Sitaxsentan Efficacy And Safety Trial With A Randomized Prospective Assessment Of Adding Sildenafil (SR-PAAS) (NCT NCT00795639)

Last Updated: 2015-03-24

Results Overview

6 MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety. Change is Week 12 results minus baseline results.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

183 participants

Primary outcome timeframe

Baseline/Day 1 and Week 12

Results posted on

2015-03-24

Participant Flow

Participant milestones

Participant milestones
Measure	Sitaxsentan Sitaxsentan 100 milligrams (mg) tablet orally once a day	Placebo Matching placebo tablet once a day
Overall Study STARTED	91	92
Overall Study Randomized and Not Treated	0	1
Overall Study COMPLETED	70	66
Overall Study NOT COMPLETED	21	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitaxsentan Sitaxsentan 100 milligrams (mg) tablet orally once a day	Placebo Matching placebo tablet once a day
Overall Study Death	1	6
Overall Study Withdrawal by Subject	1	3
Overall Study Pregnancy	1	0
Overall Study Adverse Event	5	2
Overall Study Other	0	2
Overall Study Terminated by sponsor	13	12
Overall Study Randomized and not treated	0	1

Baseline Characteristics

Sitaxsentan Efficacy And Safety Trial With A Randomized Prospective Assessment Of Adding Sildenafil (SR-PAAS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitaxsentan n=91 Participants Sitaxsentan 100 milligrams (mg) tablet orally once a day	Placebo n=91 Participants Matching placebo tablet once a day	Total n=182 Participants Total of all reporting groups
World Health Organization (WHO) Functional Class Functional Class I	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized less than 18 years	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Age, Customized 18 to 44 years	53 participants n=5 Participants	53 participants n=7 Participants	106 participants n=5 Participants
Age, Customized 45 to 64 years	30 participants n=5 Participants	26 participants n=7 Participants	56 participants n=5 Participants
Age, Customized greater than or equal to 65 years	8 participants n=5 Participants	9 participants n=7 Participants	17 participants n=5 Participants
Sex: Female, Male Female	71 Participants n=5 Participants	68 Participants n=7 Participants	139 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	23 Participants n=7 Participants	43 Participants n=5 Participants
World Health Organization (WHO) Functional Class Functional Class II	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
World Health Organization (WHO) Functional Class Functional Class III	88 Participants n=5 Participants	87 Participants n=7 Participants	175 Participants n=5 Participants
World Health Organization (WHO) Functional Class Functional Class IV	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
World Health Organization (WHO) Functional Class Functional Class Unknown	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline/Day 1 and Week 12

Population: Intent to treat population (ITT): all participants who were randomized; missing value at Week 12 imputed with last non-missing value, including the non-missing value obtained at early termination based on last observation carried forward (LOCF)

Outcome measures

Outcome measures
Measure	Sitaxsentan n=91 Participants Sitaxsentan 100 milligrams (mg) tablet orally once a day	Placebo n=92 Participants Matching placebo tablet once a day
Change From Baseline in Total Distance Walked During 6 Minute Walk Distance (6MWD) at Week 12 Baseline	343.0 Meters (m) Interval 160.0 to 442.0	330.5 Meters (m) Interval 169.0 to 456.0
Change From Baseline in Total Distance Walked During 6 Minute Walk Distance (6MWD) at Week 12 Change at Week 12	13.0 Meters (m) Interval -349.0 to 105.0	3.0 Meters (m) Interval -338.0 to 104.0

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8 and 12 or Early Termination (ET)

Population: ITT; N=number of participants with analyzable data; n=number of participants with analyzable data at the specific time point

WHO functional classification for PAH ranges from Class I (no limitation in physical activity, no dyspnea with normal activity) to Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). Improvement = reduction in functional class, deterioration = increase in functional class, no change = no change in functional class.

Outcome measures

Outcome measures
Measure	Sitaxsentan n=90 Participants Sitaxsentan 100 milligrams (mg) tablet orally once a day	Placebo n=87 Participants Matching placebo tablet once a day
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Classification at Weeks 4, 8 and 12 Week 4 - Improvement (n=90, 87)	6 participants	2 participants
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Classification at Weeks 4, 8 and 12 Week 4 - No Change (n=90, 87)	83 participants	84 participants
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Classification at Weeks 4, 8 and 12 Week 4 - Deterioration (n=90, 87)	1 participants	1 participants
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Classification at Weeks 4, 8 and 12 Week 8 - Improvement (n=86, 81)	13 participants	6 participants
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Classification at Weeks 4, 8 and 12 Week 8 - No Change (n=86, 81)	72 participants	73 participants
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Classification at Weeks 4, 8 and 12 Week 8 - Deterioration (n=86, 81)	1 participants	2 participants
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Classification at Weeks 4, 8 and 12 Week 12 - Improvement (n=80, 72)	17 participants	7 participants
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Classification at Weeks 4, 8 and 12 Week 12 - No Change (n=80, 72)	63 participants	64 participants
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Classification at Weeks 4, 8 and 12 Week 12 - Deterioration (n=80, 72)	0 participants	1 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8 and 12 or ET

Population: ITT; N=number of participants with analyzable data

TTCW defined as the number of days between first dose of study drug and the occurrence of a predefined clinical worsening event. Predefined clinical worsening events included: hospitalization for worsening PAH, on-study death, heart-lung or lung transplant, atrial septostomy or withdrawal due to the addition of any chronic medications for the treatment of worsening PAH.

Outcome measures

Outcome measures
Measure	Sitaxsentan n=91 Participants Sitaxsentan 100 milligrams (mg) tablet orally once a day	Placebo n=91 Participants Matching placebo tablet once a day
Time to Clinical Worsening (TTCW)	NA days Interval 12.0 to 86.0 Not Applicable (NA). TTCW not calculated unless at least 50 percent of participants in each treatment group had a clinical worsening event.	NA days Interval 3.0 to 73.0 TTCW not calculated unless at least 50 percent of participants in each treatment group had a clinical worsening event.

Adverse Events

Sitaxsentan

Serious events: 9 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo

Serious events: 12 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

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

Measure	Sitaxsentan n=91 participants at risk Sitaxsentan 100 milligrams (mg) tablet orally once a day	Placebo n=91 participants at risk Matching placebo tablet once a day
Gastrointestinal disorders Vomiting	2.2% 2/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.5% 5/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	2.2% 2/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	3.3% 3/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	1.1% 1/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.4% 4/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Oedema	3.3% 3/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.2% 2/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	5.5% 5/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	8.8% 8/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Alanine aminotransferase increased	4.4% 4/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.1% 1/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Aspartate aminotransferase increased	5.5% 5/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.2% 2/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Decreased appetite	1.1% 1/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.4% 4/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypokalaemia	3.3% 3/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	4.4% 4/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.1% 1/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	1.1% 1/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.4% 4/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	5.5% 5/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.2% 2/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	3.3% 3/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.2% 2/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	1.1% 1/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	3.3% 3/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.3% 3/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	7.7% 7/91 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.