Trial Outcomes & Findings for Evaluation of the Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects (NCT NCT01631864)

NCT ID: NCT01631864

Last Updated: 2015-08-10

Results Overview

The insulin sensitivity index was assessed by hyperinsulinemic euglycemic clamp (HEGC). A positive change from baseline indicates improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 98 participants
• Primary outcome timeframe: baseline, 8 weeks
• Results posted on: 2015-08-10

Participant Flow

Participant milestones

Measure	LCZ696 LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks	Amlodipine amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Overall Study STARTED	50	48
Overall Study COMPLETED	48	44
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Measure	LCZ696 LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks	Amlodipine amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Overall Study Withdrawal by Subject	0	1
Overall Study Adverse Event	2	3

Baseline Characteristics

Evaluation of the Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects

Baseline characteristics by cohort

Measure	LCZ696 n=50 Participants LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks	Amlodipine n=48 Participants amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks	Total n=98 Participants Total of all reporting groups
Age, Continuous	51.9 Years STANDARD_DEVIATION 9.6 • n=5 Participants	50.5 Years STANDARD_DEVIATION 9.4 • n=7 Participants	51.2 Years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	13 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	35 Participants n=7 Participants	76 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 8 weeks

Population: Pharmacodynamic Analysis Set (PDS): Only participants from the PDS, who had both baseline and day 56 values, were included in the analysis. The PDS included all randomized participants who received at least one dose of study drug and had no protocol deviations with relevant impact on PD data.

The insulin sensitivity index was assessed by hyperinsulinemic euglycemic clamp (HEGC). A positive change from baseline indicates improvement.

Outcome measures

Measure	LCZ696 n=48 Participants LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks	Amlodipine n=41 Participants amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Change From Baseline in Insulin Sensitivity Index	0.192 ug/kg*min/(mmol/L*pmol/L) Interval 0.025 to 0.359	0.065 ug/kg*min/(mmol/L*pmol/L) Interval -0.0116 to 0.246

SECONDARY outcome

Timeframe: 57 days

Population: Pharmacodynamic Analysis Set (PDS): Only participants from the PDS, who had both baseline and day 56 values, were included in the analysis. The PDS included all randomized participants who received at least one dose of study drug and had no protocol deviations with relevant impact on PD data.

Lipolysis was assessed through subcutaneous adipose tissue microdialysis. The actual measure type is adjusted geometric mean.

Outcome measures

Measure	LCZ696 n=47 Participants LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks	Amlodipine n=42 Participants amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Local Adipose Tissue Lipolysis, Glycerol Concentrations	82.46 micro mol/L Interval 74.53 to 91.23	65.91 micro mol/L Interval 59.22 to 73.37

SECONDARY outcome

Timeframe: 57 days

Population: Pharmacodynamic Analysis Set (PDS): Only participants from the PDS, who had both baseline and day 56 values, were included in the analysis. The PDS included all randomized participants who received at least one dose of study drug and had no protocol deviations with relevant impact on PD data.

Oxidative metabolism was assessed by indirect calorimetry.

Outcome measures

Measure	LCZ696 n=46 Participants LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks	Amlodipine n=40 Participants amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Oxidative Metabolism	0.787 carbon dioxide to oxygen ratio Interval 0.76 to 0.814	0.775 carbon dioxide to oxygen ratio Interval 0.746 to 0.804

SECONDARY outcome

Timeframe: 8 weeks

Population: Safety Analysis Set (SAS): The SAS included all randomized participants who received at least one dose of study drug.

Adverse event monitoring was conducted throughout the study.

Outcome measures

Measure	LCZ696 n=50 Participants LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks	Amlodipine n=48 Participants amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Number of Participants With Adverse Events, Serious Adverse Events and Deaths Adverse events (serious and non-serious)	30 Participants	37 Participants
Number of Participants With Adverse Events, Serious Adverse Events and Deaths Serious adverse events	1 Participants	1 Participants
Number of Participants With Adverse Events, Serious Adverse Events and Deaths Deaths	0 Participants	0 Participants

Adverse Events

LCZ696

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Amlodipine

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Measure	LCZ696 n=50 participants at risk LCZ696 400 mg plus placebo to Amlodipine once daily for 8 weeks	Amlodipine n=48 participants at risk Amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Nervous system disorders RUPTURED CEREBRAL ANEURYSM	2.0% 1/50	0.00% 0/48
Renal and urinary disorders NEPHROLITHIASIS	0.00% 0/50	2.1% 1/48

Other adverse events

Measure	LCZ696 n=50 participants at risk LCZ696 400 mg plus placebo to Amlodipine once daily for 8 weeks	Amlodipine n=48 participants at risk Amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Gastrointestinal disorders DIARRHOEA	6.0% 3/50	2.1% 1/48
General disorders OEDEMA PERIPHERAL	2.0% 1/50	33.3% 16/48
Infections and infestations NASOPHARYNGITIS	18.0% 9/50	16.7% 8/48
Nervous system disorders DIZZINESS	6.0% 3/50	2.1% 1/48
Nervous system disorders HEADACHE	8.0% 4/50	12.5% 6/48
Skin and subcutaneous tissue disorders PRURITUS	10.0% 5/50	0.00% 0/48

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 or disclosure of trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER