A Pharmacodynamic Study to Evaluate the Effect of a Fixed Dose Combination Pill on Blood Pressure

• Sponsor: Ferrer Internacional S.A. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01005290
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arms: 2
• Duration (Months): 12
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effect on systolic pressure of the 3 drugs given together in the cardiovascular combination pill (acetylsalicylic acid, simvastatin, and ramipril) to the effect on systolic pressure of ramipril given alone.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Combination pill; Drug: Ramipril	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: Cardiovascular Fixed Dose Combination Pill: A Pharmacodynamic Interaction Study to Evaluate the Effect of a Fixed Dose Combination of Acetylsalicylic Acid, Simvastatin and Ramipril (Cardiovascular Fixed Dose Combination Pill) on Blood Pressure
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Combination pill A once daily oral dose of the cardiovascular fixed dose combination pill (containing 100 mg acetylsalicylic acid, 40 mg simvastatin, and 5 mg ramipril) for one week followed by a once daily oral dose of the cardiovascular fixed dose combination pill (containing 100 mg acetylsalicylic acid, 40 mg simvastatin, and 10 mg ramipril) for 4 weeks.	Drug: Combination pill; A once daily oral dose of the cardiovascular fixed dose combination pill (containing 100 mg acetylsalicylic acid, 40 mg simvastatin, and 5 mg ramipril) for one week followed by a once daily oral dose of the cardiovascular fixed dose combination pill (containing 100 mg acetylsalicylic acid, 40 mg simvastatin, and 10 mg ramipril) for 4 weeks.
Active Comparator: Ramipril A once daily oral dose of 5 mg ramipril for one week followed by a once daily oral dose of 10 mg ramipril for 4 weeks.	Drug: Ramipril; A once daily oral dose of 5 mg ramipril for one week followed by a once daily oral dose of 10 mg ramipril for 4 weeks.

Outcome Measures

Primary Outcome Measures

1. Difference in the Adjusted Mean 24-h Systolic Pressure Results (Using ABPM) Between the Basal and the Final Visit of Each Treatment Period. [Days 7 and 36 of Period 1 and days 49 and 85 of Period 2]

   Difference in the adjusted mean 24-h systolic pressure results using ABPM (Ambulatory Blood Pressure Monitoring)in the PP population.

Secondary Outcome Measures

1. Difference in the Adjusted Mean 24-h Diastolic Pressure Results Between the Basal and the Final Visit of Each Treatment Period [Days 7 and 36 of Period 1 and days 49 and 85 of Period 2]

   Difference in the Adjusted Mean 24-h Diastolic Pressure Results (Using ABPM) Between the Basal and the Final Visit of Each Treatment Period

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects will be ≥18 years old

• Previously untreated systolic pressure result of ≥120<160 mmHg and diastolic pressure result of ≥80<100 mmHg

Exclusion Criteria:

• Subjects must not have previously received any anti-hypertensive medication

• must not have a systolic pressure <120 mmHg or ≥160 mmHg and diastolic pressure result of <80 mmHg or ≥100 mmHg

• must not have had a previous coronary artery bypass graft (CABG)

• must not have had a previous percutaneous transluminal coronary angioplasty (PTCA) with a drug-eluting stent

• must not have severe congestive heart failure (New York Heart Classification [NYHC] III-IV).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mount Sinai Medical Center	New York	New York	United States	NY 10029-6574

Sponsors and Collaborators

• Ferrer Internacional S.A.

Investigators

• Principal Investigator: Valentin Fuster, MD, PhD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ferrer Internacional S.A.
• ClinicalTrials.gov Identifier: NCT01005290
• Other Study ID Numbers: P-080646-01
• First Posted: Oct 30, 2009
• Last Update Posted: Jul 26, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by Ferrer Internacional S.A.: cardiovascular; fixed; dose; combination; pill; hypertension
• Additional relevant MeSH terms: Hypertension; Ramipril

Study Results

Participant Flow

Recruitment Details	Ninety-four subjects were screened for eligibility, participants met eligibility requirements and entered the run-in period
Pre-assignment Detail	52 subjects enrered the run-in period with ramipril 2.5 mg, 38 subjects were randomized. 20 subjects were randomized to Sequence Combination pill/ Ramipril and 18 subjects to sequence Ramipril /Combination pill.

Arm/Group Title	Pre-randomization Run-In	Combination Pill Then Ramipril	Ramipril Then Combination Pill
Arm/Group Description	Screening period with ramipril 2.5 mg once daily	After randomization, in Period 1 participants received a once daily oral dose of the cardiovascular fixed dose combination pill (containing 100 mg acetylsalicylic acid, 40 mg simvastatin, and 5 mg ramipril) for one week followed by a once daily oral dose of the cardiovascular fixed dose combination pill (containing 100 mg acetylsalicylic acid, 40 mg simvastatin, and 10 mg ramipril) for 4 weeks; participants received no intervention during wash-out; in Period 2 participants received a once daily oral dose of 5 mg ramipril for one week followed by a once daily oral dose of 10 mg ramipril for 4 weeks	After randomization, in Period 1 participants received a once daily oral dose of 5 mg ramipril for one week followed by a once daily oral dose of 10 mg ramipril for 4 weeks; participants received no intervention during wash-out; in Period 2 participants received a once daily oral dose of the cardiovascular fixed dose combination pill (containing 100 mg acetylsalicylic acid, 40 mg simvastatin, and 5 mg ramipril) for one week followed by a once daily oral dose of the cardiovascular fixed dose combination pill (containing 100 mg acetylsalicylic acid, 40 mg simvastatin, and 10 mg ramipril) for 4 weeks.
Period Title: Run-In
STARTED	52	0	0
COMPLETED	38	0	0
NOT COMPLETED	14	0	0
Period Title: Run-In
STARTED	0	20	18
COMPLETED	0	13	9
NOT COMPLETED	0	7	9
Period Title: Run-In
STARTED	0	13	9
COMPLETED	0	13	9
NOT COMPLETED	0	0	0
Period Title: Run-In
STARTED	0	13	9
COMPLETED	0	13	7
NOT COMPLETED	0	0	2

Baseline Characteristics

Arm/Group Title	Randomized Patiens
Arm/Group Description	All patients who were randomized to both treatment sequences
Overall Participants	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.8 (11.71)
Sex: Female, Male (Count of Participants)
Female	9 23.7%
Male	29 76.3%
Region of Enrollment (participants) [Number]
United States	38 100%

Outcome Measures

1. Primary Outcome

Title	Difference in the Adjusted Mean 24-h Systolic Pressure Results (Using ABPM) Between the Basal and the Final Visit of Each Treatment Period.
Description	Difference in the adjusted mean 24-h systolic pressure results using ABPM (Ambulatory Blood Pressure Monitoring)in the PP population.
Time Frame	Days 7 and 36 of Period 1 and days 49 and 85 of Period 2

Outcome Measure Data

Analysis Population Description

The PP set included all randomized subjects who received at least one dose of IMP, had a baseline primary endpoint measurement, had at least one post baseline primary endpoint measurement, and who had no major protocol deviations. The PP set served as the primary analysis set for analysis of the primary endpoint.

Arm/Group Title	Combination Pill	Ramipril
Arm/Group Description	Difference in the adjusted mean 24-h systolic pressure results (using ABPM) between the basal and the final visit of each treatment period.	Difference in the adjusted mean 24-h diastolic pressure results (using ABPM) between the basal and the final visit of each treatment period.
Measure Participants	17	17
Mean (Standard Deviation) [mm Hg]	-2.40 (8.726)	-4.40 (8.173)

2. Secondary Outcome

Title	Difference in the Adjusted Mean 24-h Diastolic Pressure Results Between the Basal and the Final Visit of Each Treatment Period
Description	Difference in the Adjusted Mean 24-h Diastolic Pressure Results (Using ABPM) Between the Basal and the Final Visit of Each Treatment Period
Time Frame	Days 7 and 36 of Period 1 and days 49 and 85 of Period 2

Outcome Measure Data

Analysis Population Description

The PP set included all randomized subjects who received at least one dose of IMP, had a baseline primary endpoint measurement, had at least one post baseline primary endpoint measurement, and who had no major protocol deviations. The PP set served as the primary analysis set for analysis of the primary endpoint.

Arm/Group Title	Combination Pill	Ramipril
Arm/Group Description	Difference in the adjusted mean 24-h diastolic pressure results (using ABPM) between the basal and the final visit of each treatment period.	Difference in the adjusted mean 24-h diastolic pressure results (using ABPM) between the basal and the final visit of each treatment period.
Measure Participants	17	17
Mean (Standard Deviation) [mm Hg]	-1.85 (6.714)	-2.88 (5.731)

Adverse Events

Time Frame	Participants were followed for the whole study duration, an average of 18 weeks.
Arm/Group Title	Combination Pill		Ramipril
Arm/Group Description
All Cause Mortality
	Combination Pill		Ramipril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Combination Pill		Ramipril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Combination Pill		Ramipril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/29 (10.3%)		1/31 (3.2%)
Nervous system disorders
Headache	3/29 (10.3%)	3	1/31 (3.2%)	1

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed

More Information

Certain Agreements

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

Communications and publication must be agreed between sponsor and PI