Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Combination Aliskiren/Amlodipine in Patients Not Adequately Responding to Aliskiren Alone (NCT NCT00777946)

NCT ID: NCT00777946

Last Updated: 2011-07-12

Results Overview

After the patient had been sitting for 5 minutes, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. The difference of the msDBP at baseline from the msDBP at 8 weeks was calculated using an Analysis of Covariance (ANCOVA) model with baseline as a covariate and treatment and region as two factors.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 818 participants
• Primary outcome timeframe: Baseline, End of Study (Week 8)
• Results posted on: 2011-07-12

Participant Flow

This study consisted of a 7 day wash-out period and a 4 week single-blind run-in period prior to the 8 week double-blind period. 2 of the 820 randomized patients were randomized in error, are not included in the 818 participants enrolled in the double-blind period, did not receive study drug & are not included in the Safety and Full Analysis Sets.

Participant milestones

Measure	Aliskiren 300 mg/Amlodipine 10 mg Participants received 1 Aliskiren/Amlodipine 300/10mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg/Amlodipine 5 mg Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks.
Overall Study STARTED	283	277	260
Overall Study Safety & Full Analysis Sets	282	276	260
Overall Study COMPLETED	262	271	244
Overall Study NOT COMPLETED	21	6	16

Reasons for withdrawal

Measure	Aliskiren 300 mg/Amlodipine 10 mg Participants received 1 Aliskiren/Amlodipine 300/10mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg/Amlodipine 5 mg Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks.
Overall Study Adverse Event	11	1	3
Overall Study Lack of Efficacy	0	0	9
Overall Study Condition no longer required study drug	1	0	0
Overall Study Patient withdrew consent	3	2	3
Overall Study Lost to Follow-up	3	1	0
Overall Study Protocol deviation	2	1	1
Overall Study Randomized in error	1	1	0

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of Combination Aliskiren/Amlodipine in Patients Not Adequately Responding to Aliskiren Alone

Baseline characteristics by cohort

Measure	Aliskiren 300 mg/Amlodipine 10 mg n=283 Participants Participants received 1 Aliskiren/Amlodipine 300/10mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg/Amlodipine 5 mg n=277 Participants Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg n=260 Participants Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks.	Total n=820 Participants Total of all reporting groups
Age Continuous	54.6 years STANDARD_DEVIATION 10.67 • n=93 Participants	54.4 years STANDARD_DEVIATION 10.69 • n=4 Participants	54.7 years STANDARD_DEVIATION 10.99 • n=27 Participants	54.6 years STANDARD_DEVIATION 10.77 • n=483 Participants
Sex: Female, Male Female	120 Participants n=93 Participants	101 Participants n=4 Participants	103 Participants n=27 Participants	324 Participants n=483 Participants
Sex: Female, Male Male	163 Participants n=93 Participants	176 Participants n=4 Participants	157 Participants n=27 Participants	496 Participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline, End of Study (Week 8)

Population: Full Analysis Set (all randomized patients who received study drug). Three patients (1 in Aliskiren 300 mg/Amlodipine 10 mg group and 2 in the Aliskiren 300 mg/Amlodipine 5 mg group were excluded from the analysis due to lack of post-baseline assessment.

After the patient had been sitting for 5 minutes, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. The difference of the msDBP at baseline from the msDBP at 8 weeks was calculated using an Analysis of Covariance (ANCOVA) model with baseline as a covariate and treatment and region as two factors.

Outcome measures

Measure	Aliskiren 300 mg/Amlodipine 10 mg n=281 Participants Participants received 1 Aliskiren/Amlodipine 300/10mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg/Amlodipine 5 mg n=274 Participants Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg n=260 Participants Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks.
Change From Baseline to End of Study in the Mean Sitting Diastolic Blood Pressure (msDBP)	-13.07 mm Hg Standard Error 0.463	-10.54 mm Hg Standard Error 0.467	-5.84 mm Hg Standard Error 0.480

SECONDARY outcome

Timeframe: Baseline, End of Study (Week 8)

Population: Full Analysis Set (all randomized patients who received study drug). Three patients (1 in Aliskiren 300 mg/Amlodipine 10 mg group and 2 in the Aliskiren 300 mg/Amlodipine 5 mg group were excluded from the analysis due to lack of post-baseline assessment.

After the patient had been sitting for 5 minutes, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. The difference of the msSBP at baseline from the msSBP at 8 weeks was calculated using an ANCOVA model with baseline as a covariate and treatment and region as two factors.

Outcome measures

Measure	Aliskiren 300 mg/Amlodipine 10 mg n=281 Participants Participants received 1 Aliskiren/Amlodipine 300/10mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg/Amlodipine 5 mg n=274 Participants Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg n=260 Participants Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks.
Change From Baseline to End of Study in the Mean Sitting Systolic Blood Pressure (msSBP)	-18.04 mm Hg Standard Error 0.780	-14.43 mm Hg Standard Error 0.788	-6.42 mm Hg Standard Error 0.809

SECONDARY outcome

Timeframe: 8 weeks

Population: Safety Population consisted of all randomized participants who received study drug.

The number of participants with any Serious Adverse Event and the number of participants with Adverse Events in any system organ class.

Additional information about Adverse Events can be found in the Adverse Event Section.

Outcome measures

Measure	Aliskiren 300 mg/Amlodipine 10 mg n=282 Participants Participants received 1 Aliskiren/Amlodipine 300/10mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg/Amlodipine 5 mg n=276 Participants Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg n=260 Participants Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks.
Number of Participants With Serious Adverse Events and Adverse Events Serious Adverse Events	3 participants	4 participants	1 participants
Number of Participants With Serious Adverse Events and Adverse Events Adverse Events	85 participants	80 participants	59 participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Full Analysis Set (all randomized patients who received study drug). Three patients (1 in Aliskiren 300 mg/Amlodipine 10 mg group and 2 in the Aliskiren 300 mg/Amlodipine 5 mg group were excluded from the analysis due to lack of post-baseline assessment.

After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit.

Blood Pressure control was defined as having a mean sitting Diastolic Blood Pressure <90 and a mean sitting Systolic Blood Pressure <140.

Outcome measures

Measure	Aliskiren 300 mg/Amlodipine 10 mg n=281 Participants Participants received 1 Aliskiren/Amlodipine 300/10mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg/Amlodipine 5 mg n=274 Participants Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg n=260 Participants Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks.
Percentage of Participants Achieving Blood Pressure Control	65.5 Percentage of participants	56.5 Percentage of participants	31.5 Percentage of participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Full Analysis Set (all randomized patients who received study drug). Three patients (1 in Aliskiren 300 mg/Amlodipine 10 mg group and 2 in the Aliskiren 300 mg/Amlodipine 5 mg group were excluded from the analysis due to lack of post-baseline assessment.

After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit.

A Diastolic Blood Pressure Response was defined as a mean sitting Diastolic Blood Pressure (msDBP) <90 mmHg or a ≥ 10 mmHg reduction in msDBP from baseline.

Outcome measures

Measure	Aliskiren 300 mg/Amlodipine 10 mg n=281 Participants Participants received 1 Aliskiren/Amlodipine 300/10mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg/Amlodipine 5 mg n=274 Participants Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg n=260 Participants Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks.
Percentage of Participants Achieving a Diastolic Blood Pressure Response	83.6 Percentage of participants	77.7 Percentage of participants	51.5 Percentage of participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Full Analysis Set (all randomized patients who received study drug). Three patients (1 in Aliskiren 300 mg/Amlodipine 10 mg group and 2 in the Aliskiren 300 mg/Amlodipine 5 mg group were excluded from the analysis due to lack of post-baseline assessment.

After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit.

A Systolic Blood Pressure Response was defined as a mean sitting Systolic Blood Pressure (msSBP) <140 mmHg or a ≥ 20 mmHg reduction in msSBP from baseline.

Outcome measures

Measure	Aliskiren 300 mg/Amlodipine 10 mg n=281 Participants Participants received 1 Aliskiren/Amlodipine 300/10mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg/Amlodipine 5 mg n=274 Participants Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg n=260 Participants Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks.
Percentage of Participants Achieving a Systolic Blood Pressure Response	77.2 Percentage of participants	69.7 Percentage of participants	43.8 Percentage of participants

Adverse Events

Aliskiren 300 mg/Amlodipine 10 mg

Serious events: 3 serious events

Other events: 26 other events

Deaths: 0 deaths

Aliskiren 300 mg/Amlodipine 5 mg

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Aliskiren 300 mg

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Aliskiren 300 mg/Amlodipine 10 mg n=282 participants at risk Participants received 1 Aliskiren/Amlodipine 300/10mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg/Amlodipine 5 mg n=276 participants at risk Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg n=260 participants at risk Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks.
Ear and labyrinth disorders Vertigo	0.00% 0/282 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.36% 1/276 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/260 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).
General disorders Pyrexia	0.00% 0/282 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.36% 1/276 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/260 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).
Immune system disorders Drug hypersensitivity	0.35% 1/282 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/276 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/260 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).
Infections and infestations Lobar pneumonia	0.35% 1/282 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/276 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/260 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).
Infections and infestations Viral infection	0.00% 0/282 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.36% 1/276 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/260 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).
Injury, poisoning and procedural complications Post-traumatic pain	0.00% 0/282 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/276 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.38% 1/260 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/282 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/276 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.38% 1/260 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.35% 1/282 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/276 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/260 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/282 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.36% 1/276 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/260 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/282 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.36% 1/276 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.00% 0/260 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).

Other adverse events

Measure	Aliskiren 300 mg/Amlodipine 10 mg n=282 participants at risk Participants received 1 Aliskiren/Amlodipine 300/10mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg/Amlodipine 5 mg n=276 participants at risk Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Aliskiren 300 mg n=260 participants at risk Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks.
General disorders Oedema peripheral	9.2% 26/282 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	2.2% 6/276 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).	0.38% 1/260 • 8 weeks Safety set (all patients who received at least 1 dose of double-blind study drug).

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER