Trial Outcomes & Findings for Efficacy and Safety of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Hypertensive Patients Not Responding to Amlodipine (NCT NCT01663233)

NCT ID: NCT01663233

Last Updated: 2015-10-23

Results Overview

The change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups was measured. A greater reduction from baseline in the LCZ696 group indicates a positive treatment effect.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 266 participants
• Primary outcome timeframe: 8 weeks
• Results posted on: 2015-10-23

Participant Flow

Participant milestones

Measure	LCZ696 and Amlodipine Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Overall Study STARTED	130	136
Overall Study COMPLETED	126	129
Overall Study NOT COMPLETED	4	7

Reasons for withdrawal

Measure	LCZ696 and Amlodipine Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Overall Study Withdrawal by Subject	3	2
Overall Study Protocol Deviation	1	4
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Efficacy and Safety of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Hypertensive Patients Not Responding to Amlodipine

Baseline characteristics by cohort

Measure	LCZ696 and Amlodipine n=130 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine n=136 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.	Total n=266 Participants Total of all reporting groups
Age, Continuous	55.4 Years STANDARD_DEVIATION 9.31 • n=5 Participants	55.5 Years STANDARD_DEVIATION 9.43 • n=7 Participants	55.4 Years STANDARD_DEVIATION 9.35 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	61 Participants n=7 Participants	110 Participants n=5 Participants
Sex: Female, Male Male	81 Participants n=5 Participants	75 Participants n=7 Participants	156 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: FAS: This set included all randomized participants who received at least one dose of study medication. Among the 266 Full Analysis Set (FAS) participants, 251 participants (123 participants in the LCZ696 + amlodipine group and 128 participants in the amlodipine group) had eligible ABPM at both baseline and endpoint.

The change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups was measured. A greater reduction from baseline in the LCZ696 group indicates a positive treatment effect.

Outcome measures

Measure	LCZ696 and Amlodipine n=123 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine n=128 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP)	-13.93 mmHg Standard Error 0.56	-0.82 mmHg Standard Error 0.56

SECONDARY outcome

Timeframe: 8 weeks

Population: FAS: This set included all randomized participants who received at least one dose of study medication. Among the 266 Full Analysis Set (FAS) participants, 251 participants (123 participants in the LCZ696 + amlodipine group and 128 participants in the amlodipine group) had eligible ABPM at both baseline and endpoint.

The change in mean 24 hour maDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.

Outcome measures

Measure	LCZ696 and Amlodipine n=123 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine n=128 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Change in Mean 24-hour ABPM Diastolic Blood Pressure (maDBP)	-8.03 mmHg Standard Error 0.38	-0.33 mmHg Standard Error 0.37

SECONDARY outcome

Timeframe: 8 weeks

Population: FAS

The change in the patient's msSBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.

Outcome measures

Measure	LCZ696 and Amlodipine n=130 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine n=136 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Change in Mean Sitting Systolic Blood Pressure (msSBP)	-19.60 mmHg Standard Error 1.35	-9.34 mmHg Standard Error 1.33

SECONDARY outcome

Timeframe: 8 weeks

Population: FAS

The change in the patient's msDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.

Outcome measures

Measure	LCZ696 and Amlodipine n=130 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine n=136 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Change in Mean Sitting Diastolic Blood Pressure (msDBP)	-9.22 mmHg Standard Error 0.83	-3.96 mmHg Standard Error 0.82

SECONDARY outcome

Timeframe: 8 weeks

Population: FAS

The change in the patient's mean sitting PP from baseline to end of the study was measured. Pulse pressure measures the difference in mean sitting systolic blood pressure and mean sitting diastolic blood pressure.

Outcome measures

Measure	LCZ696 and Amlodipine n=130 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine n=136 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Change in Sitting Pulse Pressure (PP)	-10.31 mmHg Standard Error 0.90	-5.46 mmHg Standard Error 0.89

SECONDARY outcome

Timeframe: 8 weeks

Population: FAS

The number of participants achieving a systolic and diastolic blood pressure < 140/90 mmHg was measured. This outcome measure shows how well a given blood pressure treatment can achieve a given blood pressure target or goal. Participants who achieved the target blood pressure were determined based on the mean SBP and DBP measurements taken at the end of the study. If the participants' BP measurement was below the above target, they were considered to have successful blood pressure control.

Outcome measures

Measure	LCZ696 and Amlodipine n=130 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine n=136 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Number of Participants Achieving Systolic and Diastolic Blood Pressure Control (< 140/90 mmHg)	89 Participants	46 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: FAS

The number of participants who achieved successful treatment response in the msSBP of < 140mmHg or a reduction ≥ 20 mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as a having a successful response.

Outcome measures

Measure	LCZ696 and Amlodipine n=130 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine n=136 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Number of Participants Achieving Successful Response in msSBP (< 140 mmHg or a Reduction ≥ 20 mmHg From Baseline)	98 Participants	53 Participants

SECONDARY outcome

Timeframe: 8 weeks of treatment

Population: FAS

The number of participants who achieved successful treatment response in msDBP of < 90mmHg or a reduction ≥ 10mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as having a successful response.

Outcome measures

Measure	LCZ696 and Amlodipine n=130 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine n=136 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Number of Participants Achieving Successful Response in msDBP (< 90 mmHg or a Reduction ≥ 10 mmHg From Baseline)	112 Participants	95 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Safety Set: The safety set included all randomized participants who received at least one dose of study medication.

Participants were monitored for adverse events, serious adverse events and death.

Outcome measures

Measure	LCZ696 and Amlodipine n=130 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine n=136 Participants Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Number of Participants With Adverse Event Deaths	0 Participants	0 Participants
Number of Participants With Adverse Event Adverse Events (serious and non-serious)	26 Participants	29 Participants
Number of Participants With Adverse Event Serious Adverse Events	0 Participants	0 Participants

Adverse Events

LCZ696 and Amlodipine

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Amlodipine

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	LCZ696 and Amlodipine n=130 participants at risk Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Amlodipine n=136 participants at risk Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and \<180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Infections and infestations NASOPHARYNGITIS	3.8% 5/130	3.7% 5/136
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	2.3% 3/130	3.7% 5/136
Metabolism and nutrition disorders DYSLIPIDAEMIA	0.00% 0/130	3.7% 5/136
Metabolism and nutrition disorders HYPOKALAEMIA	1.5% 2/130	2.9% 4/136
Nervous system disorders DIZZINESS	2.3% 3/130	1.5% 2/136

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1 (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 or disclosure of trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER