A Study To Evaluate The Dose-Related Efficacy and Safety of PS433540 in Subjects With Hypertension

• Sponsor: Ligand Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00635232
• Collaborator: (none)
• Enrollment: 261
• Locations: 40
• Arms: 5
• Duration (Months): 9
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to learn which doses of PS433540 should be given to patients with high blood pressure to lower their blood pressure. This study will also examine how safe PS433540 is when taken by patients with high blood pressure. Approximately 720 patients will be evaluated so that about 375 patients will be entered into the treatment phase of the study and be given PS433540.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: irbesartan; Drug: placebo; Drug: PS433540; Drug: PS433540; Drug: PS433540	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 261 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo And Active-Controlled, Parallel Group Study To Evaluate The Dose-Related Efficacy And Safety Of PS433540 In Subjects With Hypertension
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Irbesartan 300mg Irbesartan 300 mg once daily	Drug: irbesartan; 300 mg (2 x 150 mg capsules) once daily for 12 weeks; Other Names: Avapro
Placebo Comparator: Placebo Blinded Placebo Treatment	Drug: placebo; placebo capsules once daily for 12 weeks
Experimental: PS433540 200mg PS433540 200mg once daily	Drug: PS433540; 200 mg (2 x 100 mg capsules) once daily for 12 weeks
Experimental: PS433540 400mg PS433540 400mg once daily	Drug: PS433540; 400 mg (4 x 100 mg capsules) once daily for 12 weeks
Experimental: PS433540 800mg PS433540 800mg once daily	Drug: PS433540; 800 mg (8 x 100 mg capsules) once daily for 12 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Mean Seated Systolic Blood Pressure (SBP) Following 12 Weeks of Treatment With PS433540 200 mg, 400 mg, 800 mg and Placebo. [12 weeks]

Secondary Outcome Measures

1. Change From Baseline in Mean Seated Diastolic Blood Pressure (DBP) Following 12 Weeks of Treatment With PS433540 200 mg, 400 mg, 800 mg and Placebo. [12 weeks]

2. The Percentage of Patients Treated With Each Dose of PS433540 Who Achieved Blood Pressure Control, Defined as <140/90 mmHg, After 12 Weeks of Treatment. [12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males or females 18 - 70 years

• Mean seated Systolic Blood Pressure (SBP) ≥ 140 mmHg and < 180 mmHg and mean seated Diastolic Blood Pressure (DBP) > 90 and < 109 mmHg at two consecutive qualifying visits (Visits 3/3.5 and Visit 4). The mean difference in DBP between the two consecutive qualifying visits must be ≤ 10 mmHg.

• Women of child-bearing potential (WOCBP) must use two reliable forms of contraception if sexually active. Alternatively, female subjects must be postmenopausal (for at least 1 year).

Exclusion Criteria:

• Subjects with serious disorders which may limit the ability to evaluate the efficacy or safety of PS433540, including cardiovascular (includes subjects who are known to have coronary artery disease), renal (including the absence of one kidney), pulmonary, hepatic, gastrointestinal (including clinically significant malabsorption), endocrine/metabolic, hematologic, neurologic and psychiatric diseases.

• History of malignancy other than adequately treated basal cell or squamous cell skin cancer.

• Subjects with a history of myocardial infarction or New York Heart Association (NYHA) class II-IV heart failure.

• Subjects with a history of cerebrovascular accident or transient ischemic attack.

• Subjects with clinically significant cardiac conduction defects, including second or third degree Atrioventricular Block (AV block), left bundle branch block, sick sinus syndrome, atrial fibrillation, atrial flutter, an accessory bypass tract, or any arrhythmia requiring medication.

• Subjects with hemodynamically significant valvular disease.

• Subjects with history of type 1 diabetes mellitus and subjects with a history of type 2 diabetes mellitus using antihyperglycemic medication (oral medication, insulin, or exenatide) are excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Advanced Clinical Research 1000 Forrest Place Suite 2 Pell City	Pell City	Alabama	United States	35128
2	Premiere Pharmaceutical Research, LLC	Tempe	Arizona	United States	85282
3	Genova Clinical Research AZ	Tucson	Arizona	United States	85741
4	Advanced Clinical Research Institute	Anaheim	California	United States	92801
5	Associated Pharmaceutical Research Center	Buena Park	California	United States	90620
6	Clinical Trials Research CA	Lincoln	California	United States	95648
7	Long Beach Center for Clinical Research	Long Beach	California	United States	90806
8	National Research Institute	Los Angeles	California	United States	90057
9	Superior Regional Research, LLC	Sacramento	California	United States	95825
10	Orange County Research Center	Tustin	California	United States	92780
11	Westlake Medical Center	Westlake Village	California	United States	91361
12	Univ. Clinical Research Deland, LLC.	Deland	Florida	United States	32720
13	Allan Graff	Ft. Lauderdale	Florida	United States	33308
14	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
15	North County Medical	Sebastian	Florida	United States	32958
16	Q Clinical Research	Decatur	Georgia	United States	30035
17	Clinical Research Atlanta	Stockbridge	Georgia	United States	30281
18	East-West Medical Research Institute	Honolulu	Hawaii	United States	96814
19	Cedar Crosse Research Center	Chicago	Illinois	United States	60607
20	Midwest Institute for Clinical Research	Indianapolis	Indiana	United States	46260
21	MD Medical Research	Oxon Hill	Maryland	United States	20745
22	Cary Medical Research	Cary	North Carolina	United States	27518
23	Metrolina Medical Research	Charlotte	North Carolina	United States	28209
24	Unifour Medical Research NC	Hickory	North Carolina	United States	28601
25	Northstate Clinical Research	Lenoir	North Carolina	United States	28645
26	Triangle Medical Research NC	Raleigh	North Carolina	United States	27609
27	Crescent Medical Research	Salisbury	North Carolina	United States	28144
28	New Hanover Medical Rersearch	Wilmington	North Carolina	United States	28401
29	Peidmont Medical Research Associates	Winston Salem	North Carolina	United States	27103
30	The Lindner Center	Cincinnati	Ohio	United States	45219
31	Delaware Smith Clinic	Delaware	Ohio	United States	43015
32	Smith Clinic	Marion	Ohio	United States	43302
33	COR Clinical Research, L.L.C	Oklahoma City	Oklahoma	United States	73103
34	Brandywine Clinical Research Center	Downingtown	Pennsylvania	United States	19335
35	Hypertension & Nephrology Inc	Providence	Rhode Island	United States	02904
36	Punzi Medical Center	Carrollton	Texas	United States	75006
37	Innovative Clinical Trials	San Antonio	Texas	United States	78229
38	IMED Research PA	San Antonio	Texas	United States	78258
39	Hampton Roads Center for Clinical Research	Norfolk	Virginia	United States	23502
40	Gemini Scientific LLC	Madison	Wisconsin	United States	53719

Sponsors and Collaborators

• Ligand Pharmaceuticals

Investigators

• Study Director: Rene Belder, MD, Ligand Pharmaceuticals
• Principal Investigator: Joel Neutel, MD, Orange County Research Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ligand Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00635232
• Other Study ID Numbers: PCO-C-006
• First Posted: Mar 13, 2008
• Last Update Posted: Sep 16, 2011
• Last Verified: Sep 1, 2011

• Keywords provided by Ligand Pharmaceuticals: Hypertension; High Blood Pressure
• Additional relevant MeSH terms: Hypertension; Irbesartan

Study Results

Participant Flow

Pre-assignment Detail	All subjects were weaned off all antihypertensive medication prior to be entered into a 4-week single-blind placebo run-in period. Subjects had to have eligible Seated systolic and diastolic BP measurements during the single-blind placebo run-in phase to be eligible for the double blind portion of the study.

Arm/Group Title	Irbesartan 300mg	Placebo	PS433540 200mg	PS433540 400mg	PS433540 800mg
Arm/Group Description	Irbesartan 300 mg once daily	Blinded Placebo Treatment	PS433540 200mg once daily	PS433540 400mg once daily	PS433540 800mg once daily
Period Title: Overall Study
STARTED	58	59	58	58	28
COMPLETED	44	39	55	48	20
NOT COMPLETED	14	20	3	10	8

Baseline Characteristics

Arm/Group Title	Irbesartan 300mg	Placebo	PS433540 200mg	PS433540 400mg	PS433540 800mg	Total
Arm/Group Description	Irbesartan 300 mg once daily	Blinded Placebo Treatment	PS433540 200mg once daily	PS433540 400mg once daily	PS433540 800mg once daily	Total of all reporting groups
Overall Participants	58	59	58	58	28	261
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	53 91.4%	52 88.1%	50 86.2%	48 82.8%	28 100%	231 88.5%
>=65 years	5 8.6%	7 11.9%	8 13.8%	10 17.2%	0 0%	30 11.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.5 (8.97)	54.2 (8.12)	53.2 (10.58)	53.4 (10.71)	51.4 (9.92)	52.9 (9.66)
Sex: Female, Male (Count of Participants)
Female	23 39.7%	30 50.8%	27 46.6%	26 44.8%	17 60.7%	123 47.1%
Male	35 60.3%	29 49.2%	31 53.4%	32 55.2%	11 39.3%	138 52.9%
Region of Enrollment (participants) [Number]
United States	58 100%	59 100%	58 100%	58 100%	28 100%	261 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Mean Seated Systolic Blood Pressure (SBP) Following 12 Weeks of Treatment With PS433540 200 mg, 400 mg, 800 mg and Placebo.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The primary efficacy population was the Full Analysys Set (FAS) population= all randomized subjects who took at least one dose of the assigned study drug and had both baseline and post-baseline mean seated SBP. Both LOCF and observed-data set approach were performed.

Arm/Group Title	Irbesartan 300mg	Placebo	PS433540 200mg	PS433540 400mg	PS433540 800mg
Arm/Group Description
Measure Participants	58	59	58	58	28
Mean (Standard Deviation) [mm Hg]	-10.7 (14.32)	1.8 (14.16)	-13.2 (13.61)	-14.2 (11.90)	-23.4 (18.70)

2. Secondary Outcome

Title	Change From Baseline in Mean Seated Diastolic Blood Pressure (DBP) Following 12 Weeks of Treatment With PS433540 200 mg, 400 mg, 800 mg and Placebo.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Irbesartan 300mg	Placebo	PS433540 200mg	PS433540 400mg	PS433540 800mg
Arm/Group Description
Measure Participants	58	59	58	58	28
Mean (Standard Deviation) [mm Hg]	-7.1 (9.19)	0.2 (9.68)	-7.2 (8.34)	-9.2 (9.10)	-14.3 (10.53)

3. Secondary Outcome

Title	The Percentage of Patients Treated With Each Dose of PS433540 Who Achieved Blood Pressure Control, Defined as <140/90 mmHg, After 12 Weeks of Treatment.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set (LOCF)

Arm/Group Title	Irbesartan 300mg	Placebo	PS433540 200mg	PS433540 400mg	PS433540 800mg
Arm/Group Description
Measure Participants	58	59	58	58	28
Number [participants]	17 29.3%	5 8.5%	21 36.2%	28 48.3%	16 57.1%

Adverse Events

Arm/Group Title	Irbesartan 300mg		Placebo		PS433540 200mg		PS433540 400mg		PS433540 800mg
Arm/Group Description	Irbesartan 300 mg once daily		Blinded Placebo Treatment		PS433540 200mg once daily		PS433540 400mg once daily		PS433540 800mg once daily
All Cause Mortality
	Irbesartan 300mg		Placebo		PS433540 200mg		PS433540 400mg		PS433540 800mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Irbesartan 300mg		Placebo		PS433540 200mg		PS433540 400mg		PS433540 800mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/59 (0%)		0/58 (0%)		1/58 (1.7%)		0/28 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	0/58 (0%)	0	0/59 (0%)	0	0/58 (0%)	0	1/58 (1.7%)	1	0/28 (0%)	0
Other (Not Including Serious) Adverse Events
	Irbesartan 300mg		Placebo		PS433540 200mg		PS433540 400mg		PS433540 800mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/58 (32.8%)		20/59 (33.9%)		10/58 (17.2%)		25/58 (43.1%)		17/28 (60.7%)
Eye disorders
Eye Disorders	0/58 (0%)		3/59 (5.1%)		0/58 (0%)		0/58 (0%)		0/28 (0%)
Gastrointestinal disorders
Abdominal Pain	0/58 (0%)		1/59 (1.7%)		1/58 (1.7%)		0/58 (0%)		2/28 (7.1%)
Diarrhoea	1/58 (1.7%)		0/59 (0%)		1/58 (1.7%)		1/58 (1.7%)		2/28 (7.1%)
Feces Discoloured	0/58 (0%)		0/59 (0%)		0/58 (0%)		0/58 (0%)		1/28 (3.6%)
Nausea	1/58 (1.7%)		0/59 (0%)		0/58 (0%)		1/58 (1.7%)		2/28 (7.1%)
Vomiting	0/58 (0%)		0/59 (0%)		0/58 (0%)		0/58 (0%)		1/28 (3.6%)
General disorders
Fatigue	3/58 (5.2%)		1/59 (1.7%)		0/58 (0%)		4/58 (6.9%)		0/28 (0%)
Oedema Peripheral	2/58 (3.4%)		1/59 (1.7%)		2/58 (3.4%)		4/58 (6.9%)		3/28 (10.7%)
Pyrexia	0/58 (0%)		0/59 (0%)		0/58 (0%)		0/58 (0%)		1/28 (3.6%)
Infections and infestations
Influenza	1/58 (1.7%)		1/59 (1.7%)		0/58 (0%)		2/58 (3.4%)		1/28 (3.6%)
Nasopharyngitis	0/58 (0%)		0/59 (0%)		2/58 (3.4%)		1/58 (1.7%)		1/28 (3.6%)
Sinusitis	2/58 (3.4%)		1/59 (1.7%)		2/58 (3.4%)		0/58 (0%)		0/28 (0%)
Tooth Abcess	1/58 (1.7%)		0/59 (0%)		0/58 (0%)		2/58 (3.4%)		1/28 (3.6%)
Upper Respiratory Tract Infection	1/58 (1.7%)		2/59 (3.4%)		0/58 (0%)		1/58 (1.7%)		0/28 (0%)
Urinary Tract Infection	0/58 (0%)		3/59 (5.1%)		0/58 (0%)		0/58 (0%)		1/28 (3.6%)
Injury, poisoning and procedural complications
Injury, Poisoning and Procedural Complications	2/58 (3.4%)		2/59 (3.4%)		2/58 (3.4%)		4/58 (6.9%)		0/28 (0%)
Investigations
Haemoglobin abnormal	0/58 (0%)		0/59 (0%)		0/58 (0%)		0/58 (0%)		1/28 (3.6%)
Metabolism and nutrition disorders
Hyperlipidaemia	2/58 (3.4%)		0/59 (0%)		0/58 (0%)		1/58 (1.7%)		0/28 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain	0/58 (0%)		0/59 (0%)		0/58 (0%)		2/58 (3.4%)		0/28 (0%)
Nervous system disorders
Dizziness	2/58 (3.4%)		2/59 (3.4%)		0/58 (0%)		2/58 (3.4%)		3/28 (10.7%)
Headache	4/58 (6.9%)		10/59 (16.9%)		0/58 (0%)		3/58 (5.2%)		2/28 (7.1%)
Migraine	2/58 (3.4%)		3/59 (5.1%)		0/58 (0%)		2/58 (3.4%)		0/28 (0%)
Psychiatric disorders
Stress	0/58 (0%)		0/59 (0%)		0/58 (0%)		0/58 (0%)		1/28 (3.6%)
Respiratory, thoracic and mediastinal disorders
Nasal Congestion	0/58 (0%)		0/59 (0%)		1/58 (1.7%)		2/58 (3.4%)		0/28 (0%)
Respiratory Tract Congestion	0/58 (0%)		1/59 (1.7%)		0/58 (0%)		0/58 (0%)		1/28 (3.6%)
Skin and subcutaneous tissue disorders
Dermatitis Contact	0/58 (0%)		0/59 (0%)		1/58 (1.7%)		1/58 (1.7%)		1/28 (3.6%)
Urticaria	2/58 (3.4%)		0/59 (0%)		0/58 (0%)		0/58 (0%)		0/28 (0%)
Vascular disorders
Flushing	0/58 (0%)		0/59 (0%)		1/58 (1.7%)		0/58 (0%)		1/28 (3.6%)
Hot Flush	0/58 (0%)		0/59 (0%)		0/58 (0%)		1/58 (1.7%)		1/28 (3.6%)
Hypertension	0/58 (0%)		0/59 (0%)		0/58 (0%)		0/58 (0%)		1/28 (3.6%)
Hypotension	1/58 (1.7%)		0/59 (0%)		1/58 (1.7%)		2/58 (3.4%)		1/28 (3.6%)

Limitations/Caveats

The 800mg dose level was discontinued from further enrollment per protocol amendment due to findings from another PS433540 trial that suggested clinical benefit beyond 500mg was expected to be limited.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.