PATH: Perindopril Amlodipine for the Treatment of Hypertension

• Sponsor: Symplmed Pharmaceuticals LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01556997
• Collaborator: (none)
• Enrollment: 837
• Locations: 48
• Arms: 3
• Duration (Months): 12
• Patients Per Site: 17.4
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the safety and efficacy of a fixed-dose combination drug compared to two other drugs (monotherapies) in controlling hypertension.

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension	Drug: XOMA 985; Drug: Amlodipine Besylate; Drug: Perindopril Erbumine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 837 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Perindopril Amlodipine for the Treatment of Hypertension (PATH): A Multicenter, Randomized, Double-Blind, Parallel-Group Study Evaluating the Efficacy and Safety of a Fixed-Dose Combination of Perindopril Arginine Plus Amlodipine Besylate Versus Perindopril Erbumine and Amlodipine Besylate in Subjects With Essential Hypertension
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: XOMA 985 fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb)	Drug: XOMA 985; PERa/AMLb capsule taken once daily by mouth for six weeks
Active Comparator: Amlodipine Besylate (AMLb)	Drug: Amlodipine Besylate; AMLb capsule taken once daily by mouth for six weeks
Active Comparator: Perindopril Erbumine (PERe)	Drug: Perindopril Erbumine; PERe capsule taken once daily by mouth for six weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to End of Treatment in the Mean Seated Trough Cuff Diastolic Blood Pressure (DBP). [Day 0 to Day 42]

Secondary Outcome Measures

1. Change From Baseline to End of Treatment in the Mean Seated Trough Cuff Systolic Blood Pressure (SBP). [Day 0 to Day 42]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Essential hypertension

• For female subjects, a negative serum pregnancy test

• Ability to provide written informed consent

Exclusion Criteria:

• Night shift workers whose work hours include midnight to 4:00 a.m.

• Secondary hypertension

• An arm size that precludes the use of the digital blood pressure monitor cuff (arm size > 42 cm)

• Renal dysfunction, severe renal impairment, bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, subjects with only 1 kidney, or post-renal transplant subjects

• Female subjects who are pregnant, planning to become pregnant

• History of malignancy within 5 years

• Primary aldosteronism

• Heart failure (NYHA functional class 3-4), hypertrophic obstructive cardiomyopathy, or hemodynamically relevant stenosis of the aortic or mitral valve

• Significant cardiac arrhythmias, MI, stroke, CABG, PTCA, unstable angina

• Known hypersensitivity to any component of the study drugs

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Huntsville	Alabama	United States
2		Muscle Shoals	Alabama	United States
3		Glendale	Arizona	United States
4		Greenbrae	California	United States
5		Los Angeles	California	United States
6		Santa Ana	California	United States
7		Denver	Colorado	United States
8		Deland	Florida	United States
9		Ft. Lauderdale	Florida	United States
10		Miami	Florida	United States
11		Palm Harbor	Florida	United States
12		Port Orange	Florida	United States
13		Marietta	Georgia	United States
14		Gurnee	Illinois	United States
15		Indianapolis	Indiana	United States
16		Wichita	Kansas	United States
17		Louisville	Kentucky	United States
18		Metairie	Louisiana	United States
19		Auburn	Maine	United States
20		Baltimore	Maryland	United States
21		Olive Branch	Mississippi	United States
22		Butte	Montana	United States
23		Berlin	New Jersey	United States
24		Greensboro	North Carolina	United States
25		Hickory	North Carolina	United States
26		Raleigh	North Carolina	United States
27		Winston-Salem	North Carolina	United States
28		Cincinnati	Ohio	United States
29		Columbus	Ohio	United States
30		Kettering	Ohio	United States
31		Lyndhurst	Ohio	United States
32		Marion	Ohio	United States
33		Oklahoma City	Oklahoma	United States
34		Tulsa	Oklahoma	United States
35		Eugene	Oregon	United States
36		Mount Pleasant	South Carolina	United States
37		Simpsonville	South Carolina	United States
38		Bristol	Tennessee	United States
39		Austin	Texas	United States
40		Corpus Christi	Texas	United States
41		Dallas	Texas	United States
42		Ft. Worth	Texas	United States
43		Houston	Texas	United States
44		Katy	Texas	United States
45		San Antonio	Texas	United States
46		Salt Lake City	Utah	United States
47		Norfolk	Virginia	United States
48		Richmond	Virginia	United States

Sponsors and Collaborators

• Symplmed Pharmaceuticals LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Symplmed Pharmaceuticals LLC
• ClinicalTrials.gov Identifier: NCT01556997
• Other Study ID Numbers: X985400
• First Posted: Mar 19, 2012
• Last Update Posted: Sep 28, 2015
• Last Verified: Aug 1, 2015

• Keywords provided by Symplmed Pharmaceuticals LLC: Hypertension; Essential Hypertension
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Amlodipine; Perindopril

Study Results

Participant Flow

Arm/Group Title	XOMA 985	Amlodipine Besylate (AMLb)	Perindopril Erbumine (PERe)
Arm/Group Description	fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb) XOMA 985: PERa/AMLb capsule taken once daily by mouth for six weeks	Amlodipine Besylate: AMLb capsule taken once daily by mouth for six weeks	Perindopril Erbumine: PERe capsule taken once daily by mouth for six weeks
Period Title: Overall Study
STARTED	279	280	278
COMPLETED	253	252	246
NOT COMPLETED	26	28	32

Baseline Characteristics

Arm/Group Title	XOMA 985	Amlodipine Besylate (AMLb)	Perindopril Erbumine (PERe)	Total
Arm/Group Description	fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb) XOMA 985: PERa/AMLb capsule taken once daily by mouth for six weeks	Amlodipine Besylate: AMLb capsule taken once daily by mouth for six weeks	Perindopril Erbumine: PERe capsule taken once daily by mouth for six weeks	Total of all reporting groups
Overall Participants	279	280	278	837
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	261 93.5%	262 93.6%	254 91.4%	777 92.8%
>=65 years	18 6.5%	18 6.4%	24 8.6%	60 7.2%
Sex: Female, Male (Count of Participants)
Female	134 48%	130 46.4%	143 51.4%	407 48.6%
Male	145 52%	150 53.6%	135 48.6%	430 51.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	47 16.8%	43 15.4%	52 18.7%	142 17%
Not Hispanic or Latino	232 83.2%	237 84.6%	226 81.3%	695 83%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	2 0.7%	1 0.4%	1 0.4%	4 0.5%
Native Hawaiian or Other Pacific Islander	3 1.1%	0 0%	1 0.4%	4 0.5%
Black or African American	95 34.1%	96 34.3%	96 34.5%	287 34.3%
White	179 64.2%	181 64.6%	180 64.7%	540 64.5%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 0.7%	0 0%	2 0.2%
Race/Ethnicity, Customized (participants) [Number]
Black	95 34.1%	96 34.3%	96 34.5%	287 34.3%
Non-black	184 65.9%	184 65.7%	182 65.5%	550 65.7%
Region of Enrollment (participants) [Number]
United States	279 100%	280 100%	278 100%	837 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to End of Treatment in the Mean Seated Trough Cuff Diastolic Blood Pressure (DBP).
Time Frame	Day 0 to Day 42

Outcome Measure Data

Analysis Population Description

The Analysis Population for the Primary Outcome (Change from baseline to end of treatment in the mean seated trough cuff diastolic blood pressure (DBP)) consists of the Intent-to-treat population for the study

Arm/Group Title	XOMA 985	Amlodipine Besylate (AMLb)	Perindopril Erbumine (PERe)
Arm/Group Description	fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb) XOMA 985: PERa/AMLb capsule taken once daily by mouth for six weeks	Amlodipine Besylate: AMLb capsule taken once daily by mouth for six weeks	Perindopril Erbumine: PERe capsule taken once daily by mouth for six weeks
Measure Participants	271	275	274
Mean (Standard Deviation) [mmHg]	-15.7 (8.38)	-13.2 (8.33)	-9.5 (8.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	XOMA 985, Amlodipine Besylate (AMLb), Perindopril Erbumine (PERe)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments	The statistical model was an analysis of covariance model with treatment as the main effect and baseline DBP (<100 mmHg versus ≥100 mmHg), current type 2 diabetes status (yes versus no), and race (black versus non-black) as covariates.
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Change From Baseline to End of Treatment in the Mean Seated Trough Cuff Systolic Blood Pressure (SBP).
Time Frame	Day 0 to Day 42

Outcome Measure Data

Analysis Population Description

The Analysis Population for the Secondary Outcome (Change from baseline to end of treatment in the mean seated trough cuff systolic blood pressure (SBP)) consists of the Intent-to-treat population for the study

Arm/Group Title	XOMA 985	Amlodipine Besylate (AMLb)	Perindopril Erbumine (PERe)
Arm/Group Description	fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb) XOMA 985: PERa/AMLb capsule taken once daily by mouth for six weeks	Amlodipine Besylate: AMLb capsule taken once daily by mouth for six weeks	Perindopril Erbumine: PERe capsule taken once daily by mouth for six weeks
Measure Participants	271	275	274
Mean (Standard Deviation) [mmHg]	-23.4 (13.86)	-19.6 (15.62)	-13.4 (14.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	XOMA 985, Amlodipine Besylate (AMLb), Perindopril Erbumine (PERe)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments	The statistical model was an analysis of covariance model with treatment as the main effect and baseline DBP (<100 mmHg versus ≥100 mmHg), current type 2 diabetes status (yes versus no), and race (black versus non-black) as covariates.
	Method	ANCOVA
	Comments

Adverse Events

Adverse Event Reporting Description	AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Arm/Group Title	XOMA 985		Amlodipine Besylate (AMLb)		Perindopril Erbumine (PERe)
Arm/Group Description	fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb) XOMA 985: PERa/AMLb capsule taken once daily by mouth for six weeks		Amlodipine Besylate: AMLb capsule taken once daily by mouth for six weeks		Perindopril Erbumine: PERe capsule taken once daily by mouth for six weeks
All Cause Mortality
	XOMA 985		Amlodipine Besylate (AMLb)		Perindopril Erbumine (PERe)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	XOMA 985		Amlodipine Besylate (AMLb)		Perindopril Erbumine (PERe)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/279 (0.4%)		3/280 (1.1%)		2/278 (0.7%)
Cardiac disorders
Acute Myocardial Infarction	0/279 (0%)	0	1/280 (0.4%)	1	0/278 (0%)	0
Gastrointestinal disorders
Lip Swelling	0/279 (0%)	0	0/280 (0%)	0	1/278 (0.4%)	1
Gastrointestinal Hemorrhage	0/279 (0%)	0	1/280 (0.4%)	1	0/278 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/279 (0%)	0	1/280 (0.4%)	1	0/278 (0%)	0
Renal and urinary disorders
Renal Failure Acute	0/279 (0%)	0	0/280 (0%)	0	1/278 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	1/279 (0.4%)	1	0/280 (0%)	0	0/278 (0%)	0
Vascular disorders
Hypotension	0/279 (0%)	0	0/280 (0%)	0	1/278 (0.4%)	1
Other (Not Including Serious) Adverse Events
	XOMA 985		Amlodipine Besylate (AMLb)		Perindopril Erbumine (PERe)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/279 (26.9%)		68/280 (24.3%)		53/278 (19.1%)
Gastrointestinal disorders
Diarrhea	3/279 (1.1%)		1/280 (0.4%)		5/278 (1.8%)
Nausea	2/279 (0.7%)		2/280 (0.7%)		4/278 (1.4%)
General disorders
Edema peripheral	20/279 (7.2%)		35/280 (12.5%)		1/278 (0.4%)
Fatigue	5/279 (1.8%)		2/280 (0.7%)		4/278 (1.4%)
Infections and infestations
Nasopharyngitis	3/279 (1.1%)		1/280 (0.4%)		0/278 (0%)
Urinary tract infection	4/279 (1.4%)		0/280 (0%)		0/278 (0%)
Investigations
Alanine amniotransferase increased	0/279 (0%)		0/280 (0%)		4/278 (1.4%)
Aspartate amniotransferase increased	1/279 (0.4%)		0/280 (0%)		3/278 (1.1%)
Blood potassium increased	0/279 (0%)		0/280 (0%)		3/278 (1.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/279 (0.7%)		2/280 (0.7%)		3/278 (1.1%)
Back pain	3/279 (1.1%)		2/280 (0.7%)		1/278 (0.4%)
Musculoskeletal pain	2/279 (0.7%)		0/280 (0%)		3/278 (1.1%)
Nervous system disorders
Headache	7/279 (2.5%)		8/280 (2.9%)		8/278 (2.9%)
Dizziness	7/279 (2.5%)		3/280 (1.1%)		4/278 (1.4%)
Renal and urinary disorders
Hematuria	2/279 (0.7%)		3/280 (1.1%)		1/278 (0.4%)
Pollakiuria	1/279 (0.4%)		4/280 (1.4%)		0/278 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	9/279 (3.2%)		2/280 (0.7%)		8/278 (2.9%)
Skin and subcutaneous tissue disorders
Erythema	3/279 (1.1%)		0/280 (0%)		1/278 (0.4%)
Rash	1/279 (0.4%)		3/280 (1.1%)		0/278 (0%)

Limitations/Caveats

[Not Specified]

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.